[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: opp-docket@epamail.epa.gov. 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:
errico.phillip@epamail.epa.gov.
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:
opp-docket@epamail.epa.gov.
Electronic comments must be submitted as an ASCII file avoiding the
use of special characters and any form of encryption.
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
