[Federal Register Volume 64, Number 19 (Friday, January 29, 1999)]
[Notices]
[Pages 4650-4652]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-2202]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-853; FRL-6055-8]


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-853, 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: Hoyt Jamerson, Registration Support 
Branch, Registration Division (7505), Office of Pesticide Programs, 
Environmental Protection Agency, 401 M St., SW, Washington, DC 20460. 
Office location, telephone number, and e-mail address: Rm. 268, Crystal 
Mall #2, 1921 Jefferson Davis Highway, Arlington, VA 22202, (703) 308-
9368; e-mail: [email protected].
SUPPLEMENTARY INFORMATION: EPA has received pesticide petitions 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 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 petitions. Additional data may be needed before EPA rules on the 
petitions.
    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-853] (including comments and data submitted 
electronically as described below). A public version of this record, 
including printed, paper versions of electronic comments, which does 
not include any information claimed as CBI, is available for inspection 
from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal 
holidays. The official record is located at the address in 
``ADDRESSES'' at the beginning of this document.
    Electronic comments can be sent directly to EPA at:
    [email protected]


    Electronic comments must be submitted as an ASCII file avoiding the 
use of special characters and any form of encryption. Comment and data 
will also be accepted on disks in Wordperfect 5.1/6.1 file format or 
ASCII file format. All comments and data in electronic form must be 
identified by the docket control number (PF-853) 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 21, 1999.

James Jones,

Director, Registration Division, Office of Pesticide Programs.

Summary of Petition

    The petitioner summary of the pesticide petitions is printed below 
as required by section 408(d)(3) of the FFDCA. The summary of the 
petitions was prepared by the petitioner and represents the views of 
the petitioner. EPA is publishing the petition summaries with minor 
editing. 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.

 Interregional Research Project Number 4 (IR-4)

PP 5E4434, 5E4559 and 7E4872,

    EPA has received pesticide petitions (5E4434, 5E4559, and 7E4872) 
from the Interregional Research Project Number 4 (IR-4), Center for 
Minor Crop Pest Management, Technology Center of New Jersey, Rutgers, 
the State University of New Jersey, 681 U.S. Highway # 1 South, North 
Brunswick, NJ 08902-3390, proposing pursuant to section 408(d) of the 
Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to 
amend 40 CFR part 180 by establishing a tolerance for residues of the 
fungicide aluminum tris (o-ethylphosphonate) (referred to in this 
document as fosetyl-Al) in or on certain raw agricultural commodities 
as follows:
    1. EPA has received an amendment to PP 5E4434 from IR-4 proposing 
to amend the time-limited tolerance established for blueberries at 40 
ppm. IR-4 requests that the tolerance for bluberries be amended by 
extending the expiration date to December 31, 2000. The time extension 
will allow IR-4 to develop additional magnitude of residue data in 
support of a permanent tolerance for blueberries.
    2. PP 5E4559 proposes the establishment of a tolerance for grapes 
at 10 parts per million (ppm). Registration for use of fosetyl-Al on

[[Page 4651]]

grapes would be limited to areas east of the Rocky Mountains based on 
the geographical representation of the residue data submitted.
    3. PP 7E4872 proposes the establishment of a tolerance for 
macadamia nuts at 0.3 ppm.
    EPA has determined that the petitions 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 
petitions. Additional data may be needed before EPA rules on the 
petitions.

A. Residue Chemistry

    1. Plant metabolism. The metabolism of fosetyl-Al in plants is 
adequately understood. Adequate data on the nature of the residues in 
plants, including identification of major metabolites and degradates of 
fosetyl-Al, are available. Radio labeled studies on the uptake, 
translocation and metabolism in plants show that the chemical proceeds 
through hydrolytic cleavage of the ethyl ester. The major residues are 
fosetyl-Al, phosphorus acid and ethanol. The tolerances are established 
for the parent only, that is fosetyl-Al. There is no reasonable 
expectation of residues occurring in eggs, milk, and meat of livestock 
and poultry since there are no livestock feed items associated with 
commodities treated with fosetyl-Al.
    2. Analytical method. Adequate methods are available for 
enforcement purposes. There are two analytical methods acceptable for 
determining residues of fosetyl-Al in plants: a gas chromatography 
method is available for enforcement of tolerance in pineapple and is 
listed as Method I in PAM, Vol. II; a gas chromatography/phosphorus 
specific flame photometric detector (FPD-P) method (Rhone-Poulenc 
Method No. 163) for citrus has undergone a successful method tryout on 
oranges and has been sent to the FDA for inclusion in PAM as Method II.

B. Toxicological Profile

    1. Acute toxicity. A complete battery of acute toxicity studies for 
fosetyl-Al technical have been conducted. The acute oral rat and 
primary dermal irritation studies indicate category IV toxicity. A 
guinea pig dermal sensitization study shows fosetyl-Al is not a skin 
sensitizer. The primary eye irritation study in rabbits shows fosetyl-
Al to be an eye irritant with Category I toxicity.
    2. Genotoxicty. Fosetyl-Al is neither mutagenic nor genotoxic. The 
genetic toxicity potential of fosetyl-Al was assessed in several 
assays.
    3. Reproductive and developmental toxicity. Rhone-Poulenc concludes 
that fosetyl-Al is not a reproductive toxicant and shows no evidence of 
estrogenic or androgenic related effects.
    i. In a 3-generation reproduction study, fosetyl-Al was 
administered to rats at dietary levels of 0, 6,000, 12,000 or 24,000 
ppm. No adverse effects on reproductive performance or pup survival 
were observed in any dose group. The lowest-observed adverse effect 
level (LOAEL) was established at 12,000 ppm based on effects on animal 
weights and urinary tract changes. The no-observed adverse effect level 
(NOAEL) for all effects was 6,000 ppm.
    ii. A teratology study in rats dosed via oral gavage at 500, 1,000 
or 4,000 milligrams/kilogram/day (mg/kg/day) showed a developmental 
NOAEL of 1,000 mg/kg. At 4,000 mg/kg, there was maternal toxicity, as 
evidenced by effects on animal weights, maternal deaths, increased 
resorptions and delayed fetal ossification.
    iii. A rabbit teratology study showed no toxic effects at oral 
doses up to 500 mg/kg.
    Effects of fosetyl-Al on fetal development were observed only in 
the rat at a dose producing severe maternal toxicity. In the absence of 
maternal toxicity, NOAEL on fetal development were observed, i.e. at 
1,000 mg/kg/day in rats or at 500 mg/kg/day in rabbits.
    4. Subchronic toxicity. In subchronic studies, no significant 
toxicity was observed even at doses exceeding the limit of 1,000 mg/kg/
day.
    5. Chronic toxicity. Chronic feeding studies have been conducted in 
dogs and rats. The LOAEL for chronic effects of fosetyl-Al is 10,000 
ppm (250 mg/kg/day) based on a 2 year feeding study with dogs fed diets 
containing 0, 10,000, 20,000 and 40,000 ppm. This NOAEL is based on a 
slight degenerative effect on the testes at the 20,000 ppm dose level. 
In the rat, calculi in the urinary bladder and related 
histopathological changes in the bladder and kidneys of males and 
females were observed at 30,000/40,000 ppm (1,500/2,000 mg/kg/day).
    6. Carcinogenicity. Long-term feeding studies were conducted with 
technical grade fosetyl-Al in mice and rats and with monosodium 
phosphite, the primary urinary metabolite of fosetyl-Al, in rats. In 
addition, a mechanistic study in rats was conducted with feeding levels 
up to 50,000 ppm. Fosetyl-Al was administered via admixture in the diet 
to CD rats at target levels of 0, 2,000, 8,000, and 30,000/40,000 ppm 
for approximately 2 years. After 2 weeks at 40,000 ppm, this dietary 
level was reduced to 30,000 ppm. Calculi in the urinary bladder were 
observed for several male and female rats at 30,000/40,000 ppm. 
Microscopic examination revealed transitional cell carcinomas and 
papillomas in the urinary bladders of high dose males. In addition, a 
statistically significant increase in adrenal pheochromocytomas (benign 
and malignant combined) was observed in males at 8,000 and 30,000/
40,000 ppm. The adrenal slides were independently reread by two 
consulting pathologists who found no significant dose-related increases 
in the incidence of pheochromocytomas or hyperplasia.
    A subsequent mechanistic study in rats conducted with dietary 
levels of 8,000, 30,000 and 50,000 ppm demonstrated that the massive 
doses of 30,000 and 50,000 ppm fosetyl-Al alter calcium/phosphorous 
homeostasis resulting in severe acute renal injury, similar to that 
observed in the chronic rat study, and the formation of calculi in 
kidneys, ureters, and bladder. Under conditions of chronic exposure, 
these effects could lead to the formation of bladder tumors as seen in 
the chronic rat study. At 8,000 ppm, no evidence of renal injury was 
observed, a result consistent with the absence of bladder tumors.
    A carcinogenicity study in rats was conducted with monosodium 
phosphite administered via dietary mixture at levels of 2,000, 8,000, 
and 32,000 ppm. No evidence of oncogenicity was observed in this study. 
A 2 year feeding/carcinogenicity study was conducted in mice fed diets 
containing fosetyl-Al at 0, 2,500, 10,000, or 20,000/30,000 ppm. The 
20,000 ppm dose was increased to 30,000 ppm during week 19 of the 
study. The NOAEL for all effects was 20,000/30,000 ppm (3,000/4,500 mg/
kg/day). There were no carcinogenic effects observed under the 
conditions of this study.
    The Office of Pesticide Programs', Health Effects Division, 
Carcinogenicity Peer Review Committee (CPRC) concluded that the 
pesticidal use of fosetyl-Al is unlikely to pose a carcinogenic hazard 
for humans given that; (i) tumors develop in rats under extreme 
conditions that are unlikely to be achieved other than under laboratory 
conditions (at a dose in excess of the OPP dose limit for 
carcinogenicity studies); (ii) tumors in rats are believed to develop 
only at doses that produce stones; (iii) human dietary exposure to 
fosetyl-Al is only about one-500,000th of the NOAEL for stone formation 
in the rat (the most sensitive experimental model); and (iv) the dose 
of fosetyl-Al which can be absorbed dermally by applicators is also 
probably too low to

[[Page 4652]]

result in stone formation. EPA has therefore chosen to use the 
Reference Dose (RfD) to quantify dietary risk to humans.
    7. Animal metabolism. Rat metabolism studies showed that most of 
the radiolabel rapidly appeared in exhaled carbon dioxide. There was 
also some radiolabel excreted in the urine as phosphite, along with a 
smaller amount as the unchanged parent compound. It appears that 
fosetyl-Al is essentially completely absorbed after ingestion and 
extensively hydrolyzed to carbon dioxide which is exhaled. The 
phosphite is excreted in the urine without further oxidation to 
phosphate. Aluminum does not appear to be absorbed to a significant 
extent from the gastrointestinal tract.
    8. Metabolite toxicology. There are no metabolites of toxicological 
concern. The tolerances are established for the parent only, that is 
fosetyl-Al.
    9. Endocrine disruption. No evidence of estrogenic or androgenic 
effects were noted in any study with fosetyl-Al. NOAEL on mating or 
fertility indices and gestation, live birth, or weaning indices were 
noted in a 3-generation rat reproduction study at doses well above 
EPA's limit of 1,000 mg/kg/day. Therefore, Rhone-Poulenc concludes that 
fosetyl-Al does not have any effect on the endocrine system.

C. Aggregate Exposure

    1. Dietary exposure--i. Food. The calculated potential dietary 
exposure for the U.S. population is 0.065760 milligram/kilogram/
bodyweight/day (mg/kg/bwt/day). Potential exposure for nursing and non-
nursing infants less than 1-year old, children aged 1 to 6 years, and 
children aged 7 to 12 years is calculated to be 0.134076, 0.116682, and 
0.069637 mg/kg/bwt/day, respectively. Chronic dietary exposure was 
estimated using established and proposed tolerance residue levels, 1987 
food consumption data, and 100% crop treated.
    ii. Drinking water. There is no established maximum contaminant 
level (MCL) or health advisory level (HAL) for fosetyl-Al. Rhone-
Poulenc expects the potential for ground water and/or surface water 
contamination by fosetyl-Al and its degradates to be very low, in most 
cases, due to the rapid degradation of the compound in soil to non-
toxic degradates under both aerobic and anaerobic conditions. Under 
aerobic laboratory conditions, the half-life of fosetyl-Al is between 1 
and 1.5 hours in loamy sand, silt loam and clay loam and 20 minutes in 
sandy loam soil. The degradation proceeds through the hydrolysis of the 
ethyl ester bond, resulting in the formation of phosphorous acid and 
ethanol. The ethanol is further degraded into carbon dioxide. An 
anaerobic aquatic soil metabolism study was conducted. When anaerobic 
conditions were established by flooding soil, the half-life was 40 
hours with silty clay loam and 14 hours with sandy loam soil.
    2. Non-dietary exposure. Considering that fosetyl-Al is applied by 
commercial applicators on about 0.03% of available lawn acres (the 
majority being commercial landscapes), the likelihood of post 
application exposure occurring, particularly in a residential 
situation, is extremely low. The use of fosetyl-Al by the homeowner 
constitutes a minor use of the product since only small quantities are 
expected to be sold in 1998. Other applications by professional 
operators, e.g. golf courses, nurseries, sod farms, present only very 
limited exposure to a limited population of adults but do not pose any 
exposure to small children. Thus, Rhone-Poulenc concludes that the 
ornamental and turf uses are not expected to add significantly to the 
aggregate exposure for fosetyl-Al, and only dietary exposure has been 
taken into consideration for risk assessment purposes.

D. Cumulative Effects

    According to Rhone-Poulenc the effects associated with fosetyl-Al 
are unlikely to be cumulative with any other compound. The formation of 
calculi and bladder tumors in rats is the only significant 
toxicological effect observed with fosetyl-Al. These effects were 
observed in rat only at a dose which not only exceeds estimated human 
exposure by several orders of magnitude but is in excess of the OPP 
dose limit for carcinogenicity studies. Therefore, an aggregate 
assessment based on common mechanisms of toxicity is not appropriate as 
exposure to humans will be well below the levels producing calculi and 
bladder tumors in rats. Further, considering the rapid elimination of 
fosetyl-Al in the rat metabolism study, any effects associated with 
fosetyl-Al are unlikely to be cumulative with any other compound. Based 
on these reasons, only the potential risks of fosetyl-Al are considered 
in the exposure assessment.

E. Safety Determination

    1. U.S. population. EPA has established an RfD of 3.0 mg/kg/day 
using a 100 fold safety factor and a NOAEL of 250 mg/kg/bodyweight/day 
from the two year feeding study in dogs. A chronic dietary risk 
assessment using established and proposed tolerance residue levels 
results in utilization of 2.2, 4.5, 3.9, and 2.3% of the RfD for the 
whole U.S. population, non-nursing infants less than 1 year old, 
children aged 1 to 6 years, and children aged 7 to 12 years, 
respectively. Thus, the dietary exposure for fosetyl-Al is well below 
the RfD of 3.0 mg/kg/day and is negligible for all segments of the 
population including infants and children. Based on a lack of acute 
toxicity and the large margins of exposure (MOE) in the chronic dietary 
assessment, Rhone-Poulenc concludes that fosetyl-Al does not pose any 
acute dietary risks.
    2. Infants and children. In assessing the potential for additional 
sensitivity of infants and children to residues of fosetyl-Al, the 
available developmental and reproductive toxicity studies and the 
potential for endocrine modulation were considered.
    Developmental toxicity studies in two species indicate that 
fosetyl-Al has no teratogenic potential at any dose level. Further, 
NOEAL on fetal development were observed in rabbits at doses up to 500 
mg/kg/day or in rats at doses up to 1,000 mg/kg/day. In a 3-generation 
rat reproduction study, NOAEL on reproductive performance or pup 
survival were observed up to 24,000 ppm (equivalent to a dose well 
above EPA's limit dose (LTD) of 1,000 mg/kg/day). Maternal and 
developmental NOAELs and LELs were comparable in all studies indicating 
no increase susceptibility of developing organisms. Further, fosetyl-Al 
has no endocrine-modulation characteristics as demonstrated by the lack 
of endocrine effects in developmental, reproductive, subchronic, and 
chronic studies. The probability of non-occupational sources of 
exposure to fosetyl-Al is negligible. Therefore, based upon the 
completeness and reliability of the toxicity data and the conservative 
exposure assessment, Rhone-Poulenc concludes that there is a reasonable 
certainty that no harm will result to infants and children from 
exposure to the residues of fosetyl-Al and no additional uncertainty 
factor is warranted.

F. International Tolerances

    There are presently no Codex maximum residue levels established for 
residues of fosetyl-Al on any crop.
[FR Doc. 99-2202 Filed 1-28-99; 8:45 am]
BILLING CODE 6560-50-F