[Federal Register Volume 62, Number 16 (Friday, January 24, 1997)]
[Notices]
[Pages 3685-3688]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-1751]


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ENVIRONMENTAL PROTECTION AGENCY
[PF-693; FRL-5583-8]


Drexel Chemical Company; Pesticide Tolerance Petition Filing

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice of filing.

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SUMMARY: This notice is a summary of a pesticide petition proposing the 
establishment of a tolerance for residues of diuron in or on the edible 
portions of catfish. The summary was prepared by the petitioner, Drexel 
Chemical Company.

DATES: Comments, identified by the docket number [PF-693], must be 
received on or before, February 24, 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.
    Comments and data may also be submitted electronically by sending 
electronic mail (e-mail) to: [email protected]. Electronic 
comments should 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 in 5.1 file format or ASCII 
file format. All comments and data in electronic form must be 
identified by docket number [PF-693]. Electronic comments on this 
proposed rule may be filed online at many Federal Depositary Libraries. 
Additional information on electronic submissions may be found below in 
this document.
    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: Phillip V. Errico, Product Manager 
(PM) 25, 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. 245, CM#2, 
1921 Jefferson Davis Highway, Arlington, VA, (703) 305-6027; e-mail: 
[email protected].

SUPPLEMENTARY INFORMATION: EPA has received pesticide petition (PP) 
6F4680 from Drexel Chemical Company, POB 13327, Memphis, TN 38133-0237, 
proposing to amend 40 CFR 180.106 by establishing a tolerance for 
residues of the herbicide diuron [3-(3,4-dichlorophenyl)-1,1-
dimethylurea] in or on the raw agricultural commodity catfish at 1 part 
per million (ppm). The proposed analytical method is gas chromatography 
(GC) with a nitrogen-phosphorous detector.
    Pursuant to section 408(d)(A)(i) of the Federal Food, Drug, and 
Cosmetic Act (FFDCA), 21 U.S.C. 346a(e), as amended, Drexel Chemical 
Company has submitted the following summary of information, data and 
arguments in support of their pesticide petition. The summary was 
prepared by Drexel Chemical Company and EPA has not fully evaluated the 
merits of the petition. EPA edited the summary to clarify that the 
conclusions and arguments were the petitioner's and not

[[Page 3686]]

necessarily EPA's and to remove certain extraneous material.

I. Petition Summary

A. Residue Chemistry

    1. Analytical method. An analytical method is available, a modified 
form of DuPont Agricultural Products method #5470. The principle of the 
determination is the hydrolysis of diuron and its metabolites by 
alkaline reflux to 3,4-dichloroanaline (3,4-DCA), followed by a 
distillation of the aniline into an acid solution. The acid distillate 
is made alkaline with concentrated base and subsequently extracted into 
an organic solvent (hexane) and analyzed by gas chromatography. With 
the modified method, recoveries exceeded 70% and the limit of 
quantitation (LOQ) is 0.01 g/g.
    2. Magnitude of the residues. Residue trials were conducted in 
contained catfish ponds on a 30, 60 and 90-day treatment schedule. In 
the 30-day treatment schedule pond, diuron residues in catfish fillet 
were between 0.8 and 0.9 ppm after the first week post treatment, and 
declined to 0.2 ppm after 8 weeks post treatment. Due to mortality from 
Proliferative Gill Disease (PGD), no catfish were available after the 
last treatment day for residue determination from the 60-day treatment 
schedule pond. Diuron residues in catfish fillet from the 90-day 
treatment schedule pond were 1.2 ppm on the last treatment day, rose 
slightly to 1.4 ppm by day 7 post treatment, and declined to 1.1 ppm by 
day 28 post treatment.
    Using data from the magnitude of the residue study, a 
pharmacokinetic model was developed that allowed the prediction of 
diuron residues in catfish fillet using a treatment schedule of 
applying 0.01 ppm diuron to the pond every 7 days for 56 days. Based on 
the model, the maximum mean fillet residue from this treatment schedule 
is predicted to be 0.75 ppm.
    The pharmacokinetic model was validated using data from an efficacy 
study. Catfish were grown in ponds treated with 0.01 ppm diuron every 7 
days. Diuron residues in catfish fillet were determined after 113 days 
of treatment. The analysis found mean fillet residues of 0.92 ppm. The 
pharmacokinetic model predicted day 113 diuron residues in catfish 
fillet of 0.89 ppm. This excellent agreement between prediction and 
found values demonstrates the utility of the model.

B. Toxicological Profile

    1. Acute toxicity. The rat acute oral single dose LD50 is 3.5 
g/kg. The rabbit acute dermal single dose LD50 is greater than 2 
g/kg of bodyweight. The rat acute inhalation LD50 is less than 2.5 
mg per liter. A primary eye irritation study in the rabbit shows that 
diuron is moderately irritating to the unwashed eye when instilled 
undiluted. A primary dermal irritation showed that diuron is not a skin 
irritant when applied undiluted. A skin sensitization study (Buehler) 
in the guinea pig shows that diuron is not a skin sensitizer when 
applied undiluted.
    2. Genotoxicity. In the CHO/HGBRT assay the results for diuron are 
negative up to cytotoxic levels in the presence of S9 activation (0.75 
mm) and in the absence of S9 metabolic activation (1.25 mm).
    For the in vivo cytogenic study in rats, diuron is clastogenic at 
5,000 mg/kg, the highest dose level tested.
    For the in vitro unscheduled DNA synthesis assay in primary rat 
hepatocytes, diuron is negative up to 20 mm, the highest concentration 
tested.
    Diuron was not considered to be mutagenic to TA97, TA98, TA100 and 
TA1535 strains of Salmonella typhimurium (Ames Salmonella plate assay) 
either with or without metabolic activation at the concentrations 
tested (-S9, 0.5, 1, 2.5, 5 and 10 g/plate; S9, 10, 25, 100 
and 250 g/plate).
    3. Developmental and reproductive toxicity. In a reproductive 
toxicity study in the rat, the no-observed effect level/lowest observed 
effect level (NOEL/LOEL) for parental/offspring systemic toxicity and 
developmental toxicity were determined to be 250 and 1,750 ppm (16.9 
and 120 mg/kg/day for males and 20.3 and 144 mg/kg/day for females), 
respectively, based on decreased body weight gain and food consumption 
in both sexes and generations. There was no evidence that diuron 
affected reproductive performance in the rat.
    In a developmental toxicity study in the rat, the maternal toxicity 
NOEL/LOEL were considered to be 16 and 80 mg/kg/day, respectively, 
based on reduction in body weight and food consumption. The 
developmental toxicity NOEL/LOEL were considered to be 80 and 400 mg/
kg/day, respectively, based on statistically significant increases in 
delayed ossification of the vertebrae and sternebrae and decreased 
fetal weights.
    In a developmental toxicity study in rabbits, the NOEL/LOEL 
maternal toxicity were considered to be 10 and 50 mg/kg/day, 
respectively, based on decreased body weight and food consumption. 
There was no evidence of developmental effects in the study.
    4. Subchronic toxicity. In a non-guideline subchronic (6-month) 
oral toxicity study in rats, the systemic NOEL of technical diuron was 
sought. The scope of the study was primarily restricted to parameters 
affecting the erythrocytes. Based on the study findings, the systemic 
NOEL of diuron could not be determined, since some findings were judged 
to be equivocal.
    5. Chronic toxicity/oncogenicity. The chronic rat oral toxicity 
study was acceptable as supplementary data. However, deficiencies exist 
in the study because several organs were not examined, such as the 
mammary glands. No NOEL was determined. The LOEL was considered to be 
25 ppm (1.02 and 1.69 mg/kg/day for males and females, respectively), 
the lowest dose level tested in this study based on increased 
erythrocyte count in females, increased hemosiderin in the spleen, 
increased spleen weight, bone marrow activation, increased 
hematopoietic marrow, decreased fat marrow, and thickened urinary 
bladder wall in males.
    The chronic oral toxicity study in dogs was acceptable. The NOEL/
LOEL in the study were considered to be 25 and 125 ppm (1.88 and 9.33 
mg/kg/day, respectively, for both males and females) based on abnormal 
blood pigments in the blood.
    The oncogenicity phase of the combined chronic toxicity/
oncogenicity study in rats was considered to be supplementary. However, 
deficiencies exist in the study because several organs were not 
examined, such as the mammary glands.
    The oncogenicity study in mice was considered to be acceptable. The 
NOEL/LOEL for systemic toxicity were considered to be 250 ppm (50.8 and 
77.5 mg/kg/day for males and females, respectively) based on decreased 
body weight gain, and increased spleen and liver weight in males, 
elevated leucocyte and reticulocyte counts, mean corpuscular volume and 
mean corpuscular hemoglobin, and bilirubin values in both sexes; 
increased incidence of intracellular pigments in renal tubules in 
females and in the spleen of males and females; increased incidence of 
hemosiderin deposits in liver cells in males; increased incidence of 
liver single cell necrosis and cell mitosis in both sexes; increased 
incidence of enlarged degenerative cells in females and of hepatopathy 
and Kupffer cells in males; increased incidence of urinary bladder 
edema and epithelial hyperplasia, thickened mucosa and enlarged uterine 
horn in females. In the study, a statistically significant increase 
(14%,  0.01) of ovarian luteoma was noted in mice of the 
2,500 ppm group as compared to the concurrent controls (6%). This value

[[Page 3687]]

was higher than the historical control incidence of 1.7% for ovarian 
luteoma tumor. Combined ovarian sex cord tumors were also increased. 
Mammary gland tumors (adenocarcinoma type A and B) in the 2,500 ppm 
group were statistically significantly higher than the concurrent 
control (12%, p  0.05 vs. 4% in the concurrent control) and 
higher than the historical control of 3.3%.

C. Aggregate Exposure

    1. Dietary exposure.--a. Food. A Registration Eligibility Document 
(RED) for diuron is not scheduled for completion until outstanding data 
requirements requested by the EPA's Office of Pesticide Programs 
Environmental Fate and Effects Division are completed. Therefore, a 
dietary exposure assessment using anticipated residues is not 
available. In the absence of a dietary exposure assessment, the 
petitioners conducted a very conservative exposure assessment with 
proposed tolerance level residues (maximum residues permitted) for all 
crops for which the technical registrants intend to provide supporting 
data. The food, ``freshwater finfish'' was included with an anticipated 
residue level of 0.75 ppm, to represent catfish consumption.
    Since freshwater finfish can come from a number of sources, 
including sport fishing, commercial catch, and aquaculture, and could 
be other popular finfish species, such as trout or tilapia, the 
consumption estimate is extremely conservative. In addition, diuron is 
applied to contained ponds used in commercial catfish production during 
a 2 to 4-month period in the summer and fall. However, the fish are 
harvested from the ponds the year round. Residue estimates for other 
foods were adjusted to reflect the percent of crop treated, based on 
USDA data.
    Exposure estimates were compared to a Reference Dose (RfD) of 0.003 
mg/kg bwt/day (mkd), which was recommended by the RfD Review Committee 
at their September 26, 1996, meeting.
    The maximum total exposure to the U. S. population for all uses of 
diuron, including the use in catfish ponds, is 0.000593 mkd, which 
represents 19.8% of the RfD. The most highly exposed subgroup of the U. 
S. population was non-hispanic other than black or white (e.g., 
asians), which had a total exposure of 0.000787 mkd, representing 26.6% 
of the RfD.
    Exposure to all infants was 0.001537 mkd (51.2% of the RfD), and 
exposure to non-nursing infants less than a year old was 0.000675 mkd 
(63.3% of the RfD). Exposure to children from 1 to 6 years old was 
0.001386 (46.2% of the RfD), and exposure to children 7 to 12 years old 
was 0.000795 mkd (26.5% of the RfD). Exposure to females of 
childbearing age (13 to 50 years of age) was 0.000435 mkd (14.5% of the 
RfD).
    b. Drinking water. Data concerning potential exposure through 
drinking water is not available. The proposed use in catfish ponds is 
not expected to add potential exposure to drinking water. Contained 
catfish ponds are drained for levee repair every 5 to 10 years. The 
water is returned to the pond to the greatest extent possible after the 
repair. In some cases, the water may be released to a ditch or a 
stream. Because market catfish are harvested from the ponds year round 
as the catfish in a pond reach marketable size, the repair work is not 
seasonal, but completed on a staggered basis, and does not necessarily 
occur during the time of year when diuron may be applied to the pond 
waters. Diuron is moderately toxic, there have been detections in 
groundwater, and it has low to intermediate mobility in fine to coarse 
textured soils and freshwater sediment (according to the Diuron 
Environmental Fate Profile completed for the U.S. EPA by Dynamac, dated 
June 10, 1982, pp 37-49). Based on these three factors, a conservative 
10% of exposure has been reserved for drinking water.
    2. Non-dietary exposure. Diuron is not expected to be used in 
residential settings. However, some registered product labels include 
uses, while not intended for residential use, could conceivably result 
in residential exposure. These uses include application to ornamentals, 
use as a wood preservative (algicide in boat paints), or application to 
turf. A conservative 5% of the total exposure has been reserved to 
account for the uses which could potentially result in residential or 
lawn use.

D. Cumulative Effects

    Linuron is the only chemical, registered in the United States as a 
pesticide, which is chemically similar to diuron. Despite the 
structural similarity, based on publicly available information, some of 
their toxicological activities differ significantly. In the 
carcinogenicity studies, mice treated with 2,500 ppm diuron developed 
mammary adenocarcinomas and ovarian luteomas. Rats treated with 2,500 
ppm diuron developed urinary bladder carcinomas. Mammary glands were 
not evaluated in this study. For linuron, mice in the carcinogenicity 
study developed hepatocellular adenomas. Rats developed testicular 
carcinomas which were not hormone dependant. The carcinogen 
classification of diuron is currently under review. Linuron is 
considered a Group C carcinogen (without Q*) Non-tumor lesions in rats 
administered diuron included anemia and an increased reticulocyte 
count. In the chronic linuron study, there was a decrease in the 
reticulocyte count.
    Based on these considerations, there is insufficient evidence to 
determine if cumulative toxicity will occur.

E. Safety Determination

    1. U. S. population. Maximum exposure to the U. S. population 
resulting from the use of diuron, including the use in catfish ponds, 
is not expected to exceed 0.000593 mkd, representing 19.8% of the RfD. 
After adding 10% for potential drinking water and 5% for potential 
residential/lawn exposure, the total exposure represents only 34.8% of 
the RfD. Therefore, there is a reasonable certainty of no harm 
resulting from aggregate exposure of diuron to the general population.
    2. Infants and children. Maximum exposure to the most highly 
exposed infants and children subgroup, non-nursing infants less than a 
year old, is not expected to exceed 0.001900 mkd, which represents 
63.3% of the RfD. After adding 10% for potential drinking water 
exposure, and 5% for potential residential/lawn exposure, the total 
exposure to this subgroup represents only 78.3% of the RfD. Therefore, 
there is a reasonable certainty of no harm resulting from aggregate 
exposure of diuron to infants and children.
    These results represent very conservative consumption and residue 
levels. An exposure estimate based on anticipated residues for all 
foods, and consumption of farm-raised catfish only, would result in a 
greatly diminished risk.

F. International Tolerances

    A maximum residue level has not been established for diuron by the 
Codex Alimentarius Commission.

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-693].
    A record has been established for this notice of filing under 
docket control number [PF-693] (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.,

[[Page 3688]]

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 may 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.
    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 to printed, paper form as 
they are received and will place the paper copies in the official 
notice record which will also include all comments submitted directly 
in writing. The official rulemaking record is the paper record 
maintained at the address in ``ADDRESSES'' at the beginning of this 
document.

List of Subjects

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

    Dated: January 16, 1997.

Stephen L. Johnson,

Director, Registration Division, Office of Pesticide Programs.

[FR Doc. 97-1751 Filed 1-23-97; 8:45 am]
BILLING CODE 6560-50-F