[Federal Register Volume 62, Number 48 (Wednesday, March 12, 1997)]
[Notices]
[Pages 11433-11437]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-5681]


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ENVIRONMENTAL PROTECTION AGENCY
[PF-716; FRL-5589-7]


AgrEvo USA Company; Pesticide Tolerance Petition Filing

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice of filing.

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[[Page 11434]]

SUMMARY: This notice announces the filing of a pesticide petition 
proposing regulations establishing tolerances for residues of 
propamocarb (propyl-3-[dimethyl-amino] propylcarbamate) hydrochloride 
(hereafter referred to as propamocarb) and its metabolites in or on 
potatoes and their derived commodities, as well as secondary tolerances 
in meat and milk. This notice includes a summary of the petition that 
was prepared by the petitioner, AgrEvo USA Company.

DATES: Comments, identified by the docket control number [PF-716], must 
be received on or before April 11, 1997.

ADDRESSES: By mail, submit written comments to Public Response and 
Program Resources Branch, Field Operations Division (7506C), Office of 
Pesticide 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 22202. Comments and data 
may also be submitted electronically be sending electronic mail (e-
mail) to: [email protected]. 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 in ASCII file format. All 
comments and data in electronic form must be identified by docket 
control number [PF-716]. Electronic comments on this notice may be 
filed online at many Federal Depository Libraries. Additional 
information on electronic submissions can be found below this document.
    Information submitted as a comments 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: By Mail, Connie Welch, Product Manager 
(PM) 21, Registration Division (7505C), Office of Pesticide Programs, 
Environmental Protection Agency, 401 M St., SW., Washington, DC 20460. 
Office location, telephone number, and e-mail address: Rm 227, Crystal 
Mall #2, 1921 Jefferson Davis Hwy., Arlington, VA 22202, (703) 305-
6226; e-mail: [email protected].

SUPPLEMENTARY INFORMATION: EPA has received a pesticide petition (PP) 
6F4707 from AgrEvo USA Company, Little Falls Centre One, 2711 
Centerville Rd., Wilmington, DE 19808. The petition proposes, pursuant 
to section 408 of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 
U.S.C. 346a, to amend 40 CFR part 180 by establishing tolerances for 
the Propamocarb in or on potatoes at 0.5 part per million (ppm). EPA 
has determined that the petition contains data or information regarding 
the elements set forth in section 408(d)(2); however, EPA has not fully 
evaluated the sufficieny of the submitted data at this time or whether 
the data support granting of the petition. Additional data may be 
needed before EPA rules on the petition.
    As required by section 408(d) of the FFDCA, as recently amended by 
the Food Quality Protection Act, AgrEvo included in the petition a 
summary of the petition and authorization for the summary to be 
published in the Federal Register in a notice of receipt of the 
petition. The summary represents the views of AgrEvo; EPA, as mentioned 
above, is in the process of evaluating the petition. As required by 
section 408(d)(3) EPA is including the summary as a part of this notice 
of filing. EPA may have made minor edits to the summary for the purpose 
of clarity.

I. Petition Summary

A. Propamacarb Uses

    Propamocarb is a specific pesticide with specific activity against 
several Oomycete species which cause seed, seedling, root and stem rots 
and foliar diseases in many edible crops and ornamental plants. The 
mode of action of propamocarb is different compared to other Oomycete 
fungicides, which provides for efficacy against strains that have 
developed resistance to other fungicides.

B. Metabolism and Analytical Method

    1. Analytical method. A practical analytical method utilizing gas/
liquid chromatography and N-FID or MSD is available and has been 
validated for detecting and measuring levels of propamocarb in or on 
food. The limit of quantification (LOQ) is 0.05 mg/kg (ppm).
    2. Metabolism. The absorption, distribution, metabolism and 
excretion of propamocarb has been evaluated in rats. Propamocarb is 
rapidly absorbed, extensively metabolized and rapidly eliminated, 
primarily via the urine, following oral administration. Metabolite 
profiles were similar following single and repeated oral dosing and 
following intravenous dosing. The primary route of metabolism is 
oxidative degradation with hydrolytic cleavage occurring as a secondary 
pathway.

C. Residues in Plants and Animals

    1. Nature and magnitude of the residue in plants. The fate of 
propamocarb in plants is clearly understood. Metabolism studies in 
cucumbers, potatoes and spinach demonstrated that propamocarb is 
degraded into carbon dioxide which is reincorporated into natural plant 
constituents. The primary residue found in all crops, and the only 
residue of concern, is the parent, propamocarb hydrochloride.
    More than 50 residue trials on potatoes have been conducted 
throughout the world. The results from these studies indicated that 
residues of propamocarb in raw potatoes from foliar applications were 
below the LOQ, even when applied at 2.5-times the maximum proposed 
label rate of 4.5 lb ai/A. No measurable residues of propamocarb were 
detected in any of the processed commodities following treatment at 
2.5-times the maximum proposed label rate and a shorter than proposed 
pre-harvest interval (3 days vs. the proposed 14 days). An additional 
processing study at 5-times the proposed label rate (22.5 lb a.i./acre) 
is now underway. Based on these results, tolerances are proposed for 
the residues of propamocarb in or on potato at 0.5 ppm.
    Six residue trials have been conducted on tomatoes, either in the 
greenhouse or in arid climates where no rainfall likely occurred. Based 
on these data, AgrEvo USA expects that residues in tomatoes would not 
exceed 0.3 ppm when used as proposed. Typical residues are anticipated 
to be significantly lower.
    2. Nature and magnitude of the residue in animals. Data are not yet 
available on the metabolism of propamocarb in livestock. A cow 
metabolism study was initiated in September, 1996, and will be 
submitted to the Agency during 1997. However, in a rat metabolism 
study, propamocarb was extensively degraded and rapidly excreted, with 
>90 percent excreted in the urine within 24 hours. Therefore, AgrEvo 
believes that the potential for residues to occur in animal

[[Page 11435]]

commodities from ingestion of potato processing wastes which contain 
propamocarb residues at or below 0.05 ppm is negligible.

C. Toxicological Profile

    The toxicity of propamocarb has been evaluated by EPA as part of 
previous regulatory actions and is summarized below. The conclusions 
presented are those determined by the Agency as reported by the 
registrant.
    1. Acute toxicity. There are no acute toxicity concerns with 
propamocarb. The acute rat oral LD50 was 2,900 mg/kg in males and 
2,000 mg/kg in females. The acute rat dermal LD50 was 
3,000 mg/kg. The acute (4-hour) inhalation LC50 in rats 
was >7.9 mg/l. Propamocarb was not a skin sensitizer in guinea pigs. 
Based on these results, propamocarb hydrochloride was classified as 
Toxicity Category III for acute oral and dermal toxicity, and eye 
irritation, and Category IV for acute inhalation toxicity and skin 
irritation.
    2. Subchronic toxicity. In a 90-day feeding study, propamocarb was 
administered to albino rats at concentrations of 0, 20, 50, 100, and 
500/1,000 ppm in the diet. The only effects noted were slightly reduced 
food efficiency and body weight gains at 1,000 ppm.
    In a 90-day feeding study in beagle dogs, propamocarb was 
administered in the diet at concentrations of 0, 50, 100, 500, and 
1,000/2,000 ppm. No treatment-related findings were observed.
    A 21-day dermal toxicity study was performed with propamocarb in 
Sprague-Dawley rats at dose levels of 0, 100, 500 and 1,000 mg/kg/day, 
6 hours per day, 5 days per week over a 21-day period. No treatment 
related effects were observed.
    A 21-day dermal toxicity study was performed with propamocarb in 
rabbits at dose levels of 0, 150, 525 and 1,500 mg/kg/day, 6 hours per 
day, 5 days per week, over a 21-day period. The No Obsereved Effects 
Level (NOEL) for this study was considered by the Agency to be 150 mg/
kg/day based on dose-related skin irritation in mid- and high-dose 
animals and a decrease in weight gain in mid-dose females.
    3. Chronic toxicity/oncogenicity. A 2-year feeding chronic 
toxicity/carcinogenicity study was performed in Sprague-Dawley rats 
with propamocarb at dietary concentrations of 0, 40, 200 or 1,000 ppm. 
There was no evidence of carcinogenicity or other treatment-related 
effect except for a possible reduction in food intake in female rats at 
the highest level tested. Thus, 1,000 ppm (41 mg/kg/day) was considered 
to be the NOEL. However, this study did not satisfy the Agency's 
criteria for a Maximum Tolerated Dose (MTD). A new study at higher dose 
levels is now in progress.
    A 2-year feeding chronic toxicity/carcinogenicity study was 
performed in CD-1 mice with propamocarb at dietary concentrations of 0, 
20, 100 and 500 ppm. No evidence of carcinogenicity or toxicity was 
noted at any dose level. Thus, 1,000 ppm (53 mg/kg/day for males and 
females, respectively), was considered to be the NOEL. However, this 
study did not meet the Agency's criteria for a MTD. A new study at 
higher dose levels is now in progress.
    A 2-year feeding study was performed in beagle dogs with 
propamocarb at dietary concentrations of 0, 1,000, 3,000, 10,000 ppm. 
Decreased weight gain, decreased food efficiency and an increased 
incidence of acute gastric mucosal erosions and/or chronic erosive 
gastritis were noted in all treated groups. Thus, a NOEL for this study 
was not determined but was considered to be slightly lower than the 
lowest dose level tested (33.3 mg/kg/day).
    4. Genotoxicity. No evidence of genotoxicity was observed in a 
battery of studies including Salmonella and E. coli gene mutation 
assays, 2 mouse micronucleus assays, an in vitro mammalian cytogenetic 
assay using cultured human lymphocytes, a yeast mitotic gene conversion 
assay and a yeast mitotic recombination assay.
    5. Reproduction and developmental toxicity. In a developmental 
toxicity study, rats were administered propamocarb by gavage at dose 
levels of 0, 74, 221, 740, or 2,210 mg/kg/day on gestation days 6-19. 
The NOEL for maternal toxicity was 740 mg/kg/day based on mortality, 
clinical observations and decreased body weight gain at 2,210 mg/kg/
day. The NOEL for developmental toxicity was 221 mg/kg/day based on 
increased post-implantation loss, decreased fetal weights and increased 
incidence of minor skeletal anomalies (retarded ossification) at 740 
and/or 2,210 mg/kg/day.
    In another developmental toxicity study, rabbits were administered 
propamocarb by gavage at dose levels of 0, 15, 45, 150, 300, or 600 mg/
kg/day on gestation days 6-18. The NOEL for both maternal toxicity and 
developmental toxicity was 150 mg/kg/day, based on decreased maternal 
body weight gain and increased post-implantation loss at 300 mg/kg/day.
    A three-generation reproduction study was conducted using rats fed 
diet containing propamocarb at dietary concentrations of 0, 40, 200, 
and 1,000 ppm for 100 days and then continuously through 3 successive 
generations. No treatment-related effects were noted on either the 
parents or offspring.
    6. Neurotoxicity. An acute neurotoxicity study was performed in 
rats at dose levels of 0, 20, 200 and 2,000 mg/kg of propamocarb 
hydrochloride. The overall NOEL for this study was determined to be 200 
mg/kg based on decreased weight gain, soiled fur and decreased motor 
activity in males and/or females at 2,000 mg/kg.
    A 90-day neurotoxicity study was conducted in rats at dietary 
concentrations of propamocarb hydrochloride of 0, 200, 2,000 and 20,000 
ppm. No evidence of neurotoxicity (FOB, motor activity or 
neuropathology) was observed at any dose level. Plasma, red blood cell 
and brain cholinesterase levels were also not affected. The NOEL was 
determined to be 2,000 ppm (142 mg/kg/day) based on decreased weight 
gain at 20,000 ppm.
    7. Endocrine effects. No special studies have been conducted to 
investigate the potential of propamocarb 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 yet no such effects were detected. Thus, 
the potential for propamocarb to produce any significant endocrine 
effects is considered to be minimal.

E. Aggregate Exposure

    Propamocarb is registered for non-food uses on turf and ornamental 
plants (BANOL Fungicide, EPA Reg. No. 45639-88). As such, non-
occupational exposure would include exposures resulting from 
consumption of potential residues in food or water, as well as exposure 
to residues from applications to golf courses, commercial and 
ornamental turf, home lawns, sod farms, and ornamental plants. There 
are no acute toxicity concerns with propamocarb. Thus, only chronic 
exposures are being addressed here.
    1. Dietary exposure (food). Potential dietary exposures from food 
under the proposed tolerances and potential emergency use time-limited 
tolerances were estimated using the Exposure 1 software system (TAS, 
Inc.) and the 1977-78 USDA consumption data. For the purposes of this 
assessment, AgrEvo USA has made the very conservative

[[Page 11436]]

assumption that 100 percent of all commodities will contain propamocarb 
residues and that all of those residues will be at the proposed 
tolerance levels. (of: 0.05 ppm in potato tubers (whole RAC), and the 
meat, milk, fat, liver, kidney, and meat by-products of cattle, goats, 
hogs, horses, and sheep; and for future time-limited tolerances 
supporting section 18 Emergency Uses, 0.3 ppm in tomatoes (whole RAC); 
1.0 ppm in tomato juice, puree, and catsup; 3.0 ppm in tomato paste). 
Thus, this estimate should result in a gross overestimation of actual 
human exposure. Copies of these dietary exposure analyses are appended 
to this document.
    2. Dietary exposure (drinking water). The potential for propamocarb 
to leach into groundwater has been assessed in four terrestrial field 
dissipation studies conducted in several states and on various soil 
types. These studies were conducted using rates recommended for 
application to turf, which are approximately 24 lb a.i./acre, six times 
(6X) higher than the total rate recommended for use in potatoes and 
tomatoes. The degradation of propamocarb in these studies was rapid, 
with half-lives ranging from a low of 6 days to a high of 17 days. This 
compound adsorbs strongly to soil, having a moderately high soil 
adsorption coefficient (Kads) of 5.2 and a Koc of 359 in sandy loam 
soil. The compound did not leach under any of the various climatic test 
conditions, in contrast to it s high solubility in water, and did not 
exhibit mobility in either acidic or alkaline soil types. Based on 
these environmental fate data and the anticipated conditions of use, 
the potential for movement of propamocarb into groundwater is very low, 
and as such the potential contribution of any such residues to the 
total dietary intake of propamocarb will be negligible. No Maximum 
Contaminant Level or Health Advisory Level for residues of propamocarb 
in drinking water has been established.
    3. Non-dietary exposure. As a professional use turf and ornamental 
fungicide, propamocarb is used primarily (>90 percent of use) on golf 
courses for control of Pythium blight (BANOL Fungicide, EPA Reg. No. 
45639-88). Some limited use of BANOL occurs on ornamental plants 
produced in greenhouses or containers, and to a very limited extent on 
sod farms or by professional lawn care applicators to commercial turf. 
The product is rarely used on homeowner turf due to the fact that the 
diseases it controls (Pythium, Phytophthora) occurs primarily in high 
fertility, high maintenance turf (e.g. golf courses), not in homeowner 
turf. Thus, although non-dietary exposures have not been quantified, 
AgrEvo USA expects them to be minimal since they will occur primarily 
to golfers who will be wearing shoes and socks and who will not enter 
previously treated areas until after the grass has dried. Furthermore, 
based on the limited frequency of use (no more than three applications 
per year), these non-food uses for propamocarb are not likely to result 
in potential chronic exposure and thus should not be factored into a 
chronic exposure assessment.

G. Cumulative Effects

    The potential for cumulative effects of propamocarb and other 
substances having a common mechanism of toxicity must also be 
considered. The precise mechanism of toxicity for propamocarb is 
unknown. Although a member of the carbamate group of pesticides, 
propamocarb is not an n-methyl carbamate, and demonstrated no 
inhibitory effects on blood or brain cholinesterase following either 
acute or repeated oral administrations to rats and dogs. In vitro 
studies using rat or dog blood plasma showed very slight cholinesterase 
inhibitory effects only at extremely high dose levels, equivalent to 
about 2,200 mg/kg bodyweight. This level is 20,000X the established 
Reference Dose for propamocarb. Thus, AgrEvo USA anticipates no 
cumulative effects with other substances.

H. Safety Determinations

    1. U.S. population. The Agency has previously established a 
Reference Dose (RfD) value of 0.11 mg/kg/day for propamocarb based on a 
LOEL of 1,000 ppm (33.3 mg/kg/day) from a 2-year dog chronic toxicity 
study, applying an uncertainty factor of 100 to account for 
interspecies extrapolation and intraspecies variation, plus an 
additional factor of 3 to account for the lack of a NOEL. The FAO/WHO/
JMPR have recommended an Acceptable Daily Intake (ADI) of 0.1 mg/kg/
day.
    Using the conservative (worst-case) dietary exposure assumptions 
described above in paragraph E. 1., chronic dietary exposure will 
utilize only 1 percent of the RfD for the U.S. population. There is 
generally no concern for exposures below 100 percent of the RfD since 
it represents the level at or below which daily aggregate exposure over 
a lifetime will not pose appreciable risks to human health. Thus, 
AgrEvo USA concludes that there is a reasonable certainty that no harm 
will result to the U.S. population in general from aggregate exposure 
to propamocarb residues.
    2. Infants and children. Data from rat and rabbit developmental 
toxicity studies and rat multigeneration 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 pre-natal and post-natal exposure to the 
pesticide.
    No treatment-related effects to either parental animals or 
offspring were noted in a three-generation rat reproduction study at 
dose levels up to 1,000 ppm (33.3 mg/kg/day). No evidence of 
teratogenicity was noted in either rat or rabbit developmental toxicity 
studies, even at maternally toxic dose levels. Increased post-
implantation loss was noted in the rabbit study, but only at maternally 
toxic dose levels. The NOEL for both maternal and developmental 
toxicity in rabbits was 150 mg/kg/day. Decreased fetal weights, 
increased post-implantation loss and retarded ossification were noted 
in rats, and the developmental NOEL of 221 mg/kg/day was lower than the 
maternal NOEL of 740 mg/kg/day. However, the Agency has concluded that 
due to the high dose at which fetal toxicity was observed, no definite 
conclusion can be made regarding developmental toxicity in this study.
    FFDCA section 408 provides that the Agency may apply an additional 
safety factor for infants and children to account for pre- and post-
natal toxicity or incompleteness of the database. The toxicology 
database for propamocarb regarding potential pre- and post-natal 
effects in children is complete according to existing Agency data 
requirements and does not indicate any particular developmental or 
reproductive concerns. Furthermore, the previously established RfD of 
0.11 mg/kg/day, which is based on a 33.3 mg/kg/day LOEL from the 2-year 
dog feeding study, already provides for a safety factor of 1,364 
relative to the 150 mg/kg/day developmental NOEL from the rat 
developmental toxicity study. Thus, AgrEvo USA considers the existing 
RfD of 0.11 mg/kg/day to be appropriate for assessing potential risks 
to infants and children and an additional uncertainty factor is not 
warranted.
    Using the conservative assumptions described above, aggregate 
exposure to propamocarb is expected to utilize 3 percent of the RfD in 
non-nursing infants and 2 percent of the RfD in children aged 1-6. 
These numbers

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would be significantly lower if anticipated residues were utilized 
rather than tolerance values. Therefore, AgrEvo concludes that there is 
a reasonable certainty that no harm will result to infants or children 
from aggregate exposure to propamocarb residues.

I. International Tolerances

    The Codex Alimentarius Commission (Codex) has established 
tolerances (MRLs) for propamocarb in the following raw agricultural 
commodities:


------------------------------------------------------------------------
                Commodity                        Part per million       
------------------------------------------------------------------------
Beetroot                                  0.2 ppm                       
Brussels sprouts                          1.0 ppm                       
Cabbage, head                             0.1 ppm                       
Celery                                    0.2 ppm                       
Cucumber                                  2.0 ppm                       
Cauliflower                               0.2 ppm                       
Lettuce, head                             10.0 ppm                      
Pepper, sweet                             1.0 ppm                       
Radish                                    5.0 ppm                       
Strawberry                                0.1 ppm                       
Tomato                                    1.0 ppm                       
------------------------------------------------------------------------

    The FAO/WHO/JMPR have recommended an Acceptable Daily Intake (ADI) 
of 0.1 mg/kg/day.

J. Conclusions

    AgrEvo USA believes that the proposed use of propamacarb on 
potatoes 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 of 1996. Moreover, the 
proposed tolerances for propamocarb in potato commodities, meat and 
milk, of 0.05 ppm, should be established.

II. Public Record

    Interested persons are invited to submit comments on this notice of 
filing. Comments must bear a notation indicating the docket control 
number, [PF-716]. All written comments filed in response to this 
petition will be available in the Public Response and Program Resources 
Branch, at the address given above from 8:30 a.m. to 4 p.m., Monday 
through Friday, except legal holidays.
    A record has been established for this notice under docket control 
number [PF-716] 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 public 
record is located in Rm. 1132 of the Public Response and Program 
Resources Branch, Field Operations Division (7506C), Office of 
Pesticide Programs, Environmental Protection Agency, Crystal Mall #2, 
1921 Jefferson Davis Highway, Arlington, VA.
    Electronic comments can be sent directly to EPA at:
    [email protected]


    Electronic comments must be submitted as ASCII file avoiding the 
use of special characters and any form of encryption.
    The official record for this notice, as well as the public version, 
as described above will be kept in paper form. Accordingly, EPA will 
transfer all comments received electronically into printed, paper form 
as they are received and will place the paper copies in the official 
record which will also include all comments submitted directly in 
writing. The official record is the paper record maintained at the 
address in ``ADDRESSES'' at the beginning of this document.

    Authority: 21 U.S.C. 346a.

List of Subjects

    Environmental protection, Administrative practice and procedure, 
Agricultural commodities, Pesticides and pests, Reporting and 
recordkeeping.

    Dated: February 26, 1997.

Peter Caulkins,
Acting Director, Registration Division, Office of Pesticide Programs.

[FR Doc. 97-5681 Filed 3-11-97; 8:45 am]
BILLING CODE 6560-50-F