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Diflubenzuron (Uniroyal). February 25, 1998. Pesticide tolerance petition for residues in or on rice at 0.02 ppm and rice straw at 0.8 ppm. Federal Register.
http://www.epa.gov/fedrgstr/EPA-PEST/1998/February/Day-25/p4812.htm
[Federal Register: February 25, 1998 (Volume 63, Number 37)]
[Notices]
[Page 9528-9532]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr25fe98-76]
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ENVIRONMENTAL PROTECTION AGENCY
[PF-795; FRL-5775-3]
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-795, must
be received on or before March 27, 1998.
ADDRESSES: By mail submit written comments to: Public Information and
Records Integrity Branch (7502C), Information Resources and Services
Division, 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 to: opp-
docket@epamail.epa.gov. 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. 119 at the
Virginia address given above, from 8:30 a.m. to 4 p.m., Monday through
Friday, excluding legal holidays.
FOR FURTHER INFORMATION CONTACT: By mail: Paul Schroeder, Registration
Division, (7505C), Office of Pesticide Programs, Environmental
Protection Agency, 401 M. St., SW., Washington, DC 20460. Office
location and telephone number: Rm. 255, CM #2, 1921 Jefferson Davis
Highway, Arlington, VA, 703-305-6602, e-mail:
schroeder.paul@epamail.epa.gov.
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-795] (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:
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. Comment and data
will also be accepted on disks in Wordperfect 5.1/6.1 or ASCII file
format. All comments and data in electronic form must be identified by
the docket control number [PF-795] 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: February 18, 1998.
James Jones,
Director, Registration Division, Office of Pesticide Programs.
Summaries of Petitions
Petitioner summaries of the pesticide petitions are printed below
as required
[[Page 9529]]
by section 408(d)(3) of the FFDCA. The summaries of the petitions were
prepared by the petitioners and 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.
Uniroyal Chemical Company
PP 6G4771
EPA has received a pesticide petition (PP 6G4771) from Uniroyal
Chemical Co., Inc., Bethany, Connecticut 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
the combined residues of the insect growth regulator, diflubenzuron and
metabolites convertible to p-chloroaniline, expressed as diflubenzuron
in or on rice at 0.02 parts per million (ppm) and rice straw at 0.8
ppm. The proposed analytical method for detecting and measuring
residues of diflubenzuron and 4-chloroaniline is gas chromatography
with electron capture detection. p-Chloroaniline is determined using an
internal standard method and detected by mass spectrometry.
Pursuant to the section 408(d)(2)(A)(I) of the FFDCA, as amended,
Uniroyal Chemical Company has submitted the following summary of
information, data and arguments in support of their pesticide petition.
This summary was prepared by Uniroyal Chemical and EPA has not fully
evaluated the merits of the petition. EPA edited the summary to clarify
that the conclusions and arguments were the petitioners and not
necessarily EPA's and to remove certain extraneous material.
A. Toxicology Profile
1. Data summary. Diflubenzuron is not acutely toxic and is not an
irritant. In a 3-week dermal toxicity study in rats the no observed
effect level (NOEL) for systemic toxicity was 20 milligrams/kilograms
(mg/kg/day). In developmental toxicity studies in rats and rabbits,
diflubenzuron was without maternal or developmental effects at doses up
to 1,000 mg/kg/day. Systemic effects were seen on parental animals in a
rat reproduction study at doses of 1,000 and 100,000 ppm; however,
there were no reproductive effects and the NOEL for reproductive
toxicity was greater than 5,000 mg/kg/day. In a chronic dog feeding
study, target organ effects were seen in the blood and liver.
Methemoglobinemia was evident at dose levels of 10 mg/kg/day and
greater. The NOEL for chronic toxicity in dogs was 2 mg/kg/day. In a
chronic rat feeding study, target organ effects were seen in the blood,
liver, spleen and bone marrow. Methemoglobinemia was evident at doses
of 160 ppm and greater. The NOEL for chronic toxicity in rats was 2 mg/
kg/day. Diflubenzuron was negative in a complete battery of
mutagenicity assays. In a mouse oncogenicity study, diflubenzuron was
negative at doses up to 1,429 mg/kg/day. Additionally, diflubenzuron
was negative for carcinogenicity in a rat chronic feeding study at
doses up to 500 mg/kg/day. None of the studies conducted on
diflubenzuron have provided evidence of endocrine organ involvement.
2. Acute toxicity. Studies for diflubenzuron technical indicate the
acute oral toxicity in rats and mice is >4,640 mg/kg, and the acute
dermal toxicity in rats is >10,000 mg/kg. The acute inhalation
LC<INF>50</INF> in rats is >35 mg/l (6 hours). Diflubenzuron technical
is not an eye or skin irritant to rabbits, and is not a dermal
sensitizer in guinea pigs.
To assess subacute dermal toxicity, diflubenzuron was applied to
the backs of male and female CD rats for 3 weeks at dose levels of 20,
500 and 1,000 mg/kg/day. Hematology evaluation showed reductions in red
blood cell (RBC), hemoglobin (Hgb) and hematocrit values at 500 and
1,000 mg/kg/day. An increased incidence of polychromasia, hypochromasia
and anisocytosis was seen at 500 and 1,000 mg/kg/day. An increase in
methemoglobin and sulfhemoglobin values was seen at 1,000 mg/kg/day.
The NOEL for systemic toxicity was 20 mg/kg/day.
3. Developmental/reproductive effects. In a rat developmental
toxicity study, diflubenzuron was administered by oral gavage to
pregnant female rats at dosage levels of 0, 1, 2 and 4 mg/kg/day. No
treatment related effects were seen. A subsequent study was conducted
in pregnant Sprague Dawley rats at a dose of 0 and 1,000 mg/kg/day. No
maternal toxicity was observed. The incidence of fetuses with skeletal
abnormalities was slightly increased in the treated group, but was
within historical background range. The NOEL for maternal and
developmental toxicity in rats was greater than 1,000 mg/kg/day.
Diflubenzuron was also administered by oral gavage to pregnant New
Zealand White rabbits at dosage levels of 0, 1, 2 and 4 mg/kg/day. No
treatment related effects were seen. A subsequent study was conducted
in pregnant rabbits at a dose of 0 and 1,000 mg/kg/day. No maternal or
developmental toxicity was seen. The NOEL for maternal and
developmental toxicity in rabbits was greater than 1,000 mg/kg/day.
In a rat reproduction study, diflubenzuron was fed to two
generations of male and female rats at dietary concentrations of 0, 10,
20, 40, and 160 ppm. No effects were seen on parental body weight gain
and there were no reproductive effects. A subsequent study was
conducted on 1-generation (one litter) of rats at dietary
concentrations of 0, 1,000 and 100,000 ppm. Systemic effects were seen
in adults at these doses but there was no effect on reproductive
parameters. The NOEL for reproductive toxicity was greater than 100,000
ppm (5 g/kg/day).
4. Chronic effects. Diflubenzuron was given by capsule to male and
female Beagle dogs for one year at dose levels of 0, 2, 10, 50 and 250
mg/kg/day. Body weight gain was slightly reduced in females at 250 mg/
kg/day. Absolute liver and spleen weights were increased in males given
50 and 250 mg/kg/day. A reduction in hemoglobin and mean corpuscular
hemoglobin concentration, with an elevation in reticulocyte count, was
seen at 50 and 250 mg/kg/day. Methemoglobin and sulfhemoglobin values
were increased at doses of 10 mg/kg/day and greater. Histopathological
findings were limited to pigmented macrophages and Kupffer cells in the
liver at doses of 50 and 250 mg/kg/day. The NOEL for chronic toxicity
in dogs was 2 mg/kg/day.
Diflubenzuron was fed to male and female Sprague Dawley rats for 2
years at dose levels of 0, 156, 625, 2,500 and 10,000 ppm.
Methemoglobin values were elevated in female rats at all dose levels
and in male rats at the two highest dose levels. Sulfhemoglobin was
elevated in females, only, at dose levels of 2,500 and 10,000 ppm. Mean
corpuscular volume (MCV) and reticulocyte counts were increased in high
dose females. Spleen and liver weights were elevated at the two highest
doses. Histopathological examination demonstrated an increase in
hemosiderosis of the liver and spleen, bone marrow and erythroid
hyperplasia and areas of cellular alteration in the liver. In another
study diflubenzuron was administered to male and female CD rats for 2
years at dose levels of 0, 10, 20, 40 and 160 ppm. Elevated
methemoglobin levels were seen in high dose males and females. No
additional effects, including carcinogenic findings, were observed. The
NOEL for chronic toxicity in rats was 40 ppm (2 mg/kg/day).
[[Page 9530]]
5. Carcinogenicity. A 91-week oncogenicity study in CFLP mice was
conducted at doses of 0, 16, 80, 400, 2,000 and 10,000 ppm. There was
no increase in tumor incidence as a result of diflubenzuron
administration. Target organ effects included: increased methemoglobin
and sulfhemoglobin values, Heinz bodies, increased liver and spleen
weight, hepatocyte enlargement and vacuolation, extramedullary
hemopoiesis in the liver and spleen, siderocytosis in the spleen and
pigmented Kupffer cells. A NOEL for these effects was 16 ppm (2 mg/kg/
day).
Diflubenzuron was fed to male and female Sprague Dawley rats for 2
years at dose levels of 0, 156, 625, 2,500 and 10,000 ppm.
Methemoglobin values were elevated in female rats at all dose levels
and in male rats at the two highest dose levels. Blood sulfhemoglobin
was elevated in females, only, at dose levels of 2,500 and 10,000 ppm.
MCV and reticulocyte counts were increased in high dose females. Spleen
and liver weights were elevated at the two highest doses.
Histopathological examination demonstrated an increase in hemosiderosis
of the liver and spleen, bone marrow and erythroid hyperplasia and
areas of cellular alteration in the liver. There was no increase in
tumor formation. In another study diflubenzuron was administered to
male and female CD rats for 2 years at dose levels of 0, 10, 20, 40 and
160 ppm. Elevated methemoglobin levels were seen in high dose males and
females. No additional effects, including carcinogenic findings, were
observed.
NCI/NTP conducted chronic feeding and gavage studies with p-
chloroaniline (PCA), a minor metabolite of diflubenzuron, in Fischer
344 rats and B6C3F1 mice.
PCA was administered in the diet to Fischer 344 rats at dietary
concentrations of 250 and 500 ppm for 78 weeks, followed by a 24-week
observation period. A slight body weight depression was seen in high
dose females rats, compared to controls. Survival was reduced in high
dose males compared to controls. In male rats there was a slight
increase in uncommon fibromas or fibrosarcomas of the spleen, which was
not statistically significant. Non-neoplastic proliferative and chronic
inflammatory lesions were found in spleens of treated rats. It was
concluded that, under the conditions of the assay, sufficient evidence
was not found to establish the carcinogenicity of PCA for Fischer 344
rats.
PCA was administered 5 days/week by oral gavage, as a hydrochloride
salt in water, to male and female F344/N rats at doses of 0, 2, 6 or 18
mg/kg/day. Mean body weights of dosed rats were generally within 5% of
those of controls throughout the study. High dose animals generally
showed mild hemolytic anemia and dose-related methemolglobinemia. Non-
neoplastic lesions seen were bone marrow hyperplasia, hepatic
hemosiderosis and splenic fibrosis, suggesting treatment related
effects on the hematopoietic system. Adrenal medullary hyperplasia was
observed in high dose female rats. The incidence of uncommon sarcomas
of the spleen was significantly increased in high dose male rats. A
marginal increase in pheochromocytomas of the adrenal gland was seen in
high dose male and female rats. It was concluded that, under the
conditions of this 2 year gavage study, there was clear evidence of
carcinogenic activity of PCA hydrochloride for male F344/N rats and
equivocal evidence of carcinogenic activity of PCA hydrochloride for
female F344/N rats.
PCA was administered in the diet to B6C3F6 mice at dietary
concentrations of 2,500 and 5,000 ppm for 78 weeks followed by a 13-
week observation period. A body weight depression was seen in treated
mice of both sexes, compared to controls. An increased incidence of
hemangiomas and hemangiosarcomas in spleen, kidney, liver and other
sites was seen in treated mice of both sexes, however this increase was
not statistically significant compared to controls. Non-neoplastic
proliferative and chronic inflammatory lesions were found in spleens of
treated mice. The evidence was considered insufficient to conclusively
relate the hemangiomatous tumors in mice to compound administration. It
was concluded that, under the conditions of the assay, sufficient
evidence was not found to establish the carcinogenicity of PCA for
B6C3F1 mice.
PCA hydrochloride was administered 5 days/week by oral gavage to
male and female B6C3F1 mice at doses of 0, 3, 10, or 30 mg/kg/day. Mean
body weights of high dose male and female mice were generally within 5%
of those of controls throughout the study. The incidence of
hepatocellular adenomas or carcinomas (combined) was increased in a
non-dose-dependent manner in treated male mice. Metastasis of carcinoma
to the lung was seen in the high dose group. An increased incidence of
hemangiosarcomas of the liver or spleen was seen in high dose male
mice. It was concluded that, under the conditions of this 2 year gavage
study, there was some evidence of carcinogenic activity of PCA
hydrochloride for male B6C3F1 mice and no evidence of carcinogenic
activity of PCA hydrochloride for female B6C3F1 mice.
6. Mutagenicity. Diflubenzuron did not show any mutagenic activity
in point mutation assays employing S. typhimurium, S. cerevisiae, or
L5178Y Mouse Lymphoma cells. Diflubenzuron did not induce chromosomal
aberrations in Chinese Hamster Ovary cells and it did not induce
unscheduled DNA synthesis in human WI-38 cells. Diflubenzuron was also
negative in Mouse Micronucleus and Mouse Dominant Lethal assays and it
did not induce cell transformation in Balb/3T3 cells.
7. Endocrine effects. The standard battery of required studies has
been completed and evaluated to determine potential estrogenic or
endocrine effects of diflubenzuron. 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. No such effects were noted
in any of the studies with diflubenzuron.
8. Rat metabolism. Diflubenzuron (DFB) in rats at a single dose of
100 mg/kg and 5 mg/kg single and multiple oral doses depicted limited
absorption from the gastrointestinal tract. No major difference was
observed between the single and multiple doses. In single dose
treatments, after 7 days, 20 and 3% of the applied dose 5 and 100 mg/
kg, respectively, were excreted in urine while 79 and 98% of the
applied dose 5 and 100 mg/kg, respectively, were eliminated in the
feces. Very little bioaccumulation in the tissues was observed. Several
metabolites were observed in the urine which are, among others, 2,6-
diflurobenzoic acid (DFBA), 2,6-difluorophippuric acid, 2,6-
difluorobenzamide (DFBAM), and 2-hydroxydiflubenzuron (2-HDFB). An
unresolved peak that was p-chloroaniline (PCA) and/or p-
chlorophenylurea (CPU) was found. This latter peak accounted for about
2% of the administered dose (5 mg/kg). In the feces, only unchanged
parent compound was detected.
B. Aggregate Exposure
1. Dietary exposure--i. Diflubenzuron. The dietary exposure from
diflubenzuron (DFB) was estimated based on the average residue values
from the various currently labeled raw agricultural commodities (RACs)
and the proposed rice use. Percent of crop treated was also factored
into the estimate. Current animal commodity tolerances, which
[[Page 9531]]
adequately cover the rice use, were used for meat, milk, and egg
products. The dietary exposure analysis was estimated based on 1977
USDA food consumption data.
For the general U.S. population (48 states, all seasons), the
dietary exposure of diflubenzuron was estimated as 0.000706 mg/kg/day.
For nursing and non-nursing infants, the exposure was estimated as and
0.000799 and 0.003461 mg/kg/day, respectively. For children, the
exposure was 0.001888 and 0.001178 mg/kg/day for 1-6 year olds and 7-12
year olds, respectively.
ii. p-Chloroaniline and related product. The dietary exposure
estimate for PCA and related products is a conservative estimate, in
that it includes rice straw as an animal feed. Rice straw, however,
will be restricted as a animal feed, in the proposed Experimental Use
Program. The dietary exposure from p-chloroaniline (PCA) and a related
product, 4-chlorophenylurea (CPU), which have been detected in some
food products was also determined. EPA has used a 2% in vivo conversion
factor of DFB to PCA for foods derived from plant products. For
mushrooms, PCA and CPU average residue data was combined with a 2% in
vivo conversion of DFB to PCA. Calculations for levels of PCA/CPU in
animal products were based on metabolism studies, extrapolation to
anticipated animal dietary burdens and the 2% conversion of DFB to PCA.
The percent treated of each crop was also factored into the exposure
estimate.
For the general U.S. population, the dietary exposure of PCA/CPU
was estimated as 0.000001 mg/kg/day. For nursing and non-nursing
infants, the exposure was estimated as 0.000002 and 0.000006 mg/kg/day,
respectively. For children, the exposure was 0.000004 and 0.000002 mg/
kg/day for 1-6 year olds and 7-12 year olds, respectively.
2. Drinking water exposure. Diflubenzuron degrades in soil
relatively quickly with an aerobic half-life ranging from 3-7 days.
Major degradates include difluorobenzoic acid (DFBA) and CPU. DFBA is
further metabolized through decarboxylation and ring cleavage by soil
microbes whereas CPU is slowly degraded to soil-bound entities. Under
anaerobic aquatic conditions, diflubenzuron has a half-life of 34 days
with the main degradates being DFBA and CPU. In surface water,
diflubenzuron is degraded by microbes with a half-life of 5-10 days.
The soil mobility of diflubenzuron is considered quite limited based on
a number of experimental studies as well as by computer modeling. CPU
has also been shown to be relatively immobile in soil. Although DFBA
shows mobility in soil, it is rapidly degraded. Therefore, based on
results of laboratory and field studies, it is not likely that
diflubenzuron or its degradates will impact ground water quality to any
significant extent. Thus the aggregate risk to diflubenzuron does not
include drinking water.
3. Non-occupational exposure. Diflubenzuron is a restricted use
pesticide based on its toxicity to aquatic invertebrates. This
restricted use classification makes it unavailable for use by
homeowners. Occupational uses of diflubenzuron may expose people in
residential locations, parks, or forests treated with diflubenzuron.
Based on very low residues detected in forestry dissipation studies,
low dermal absorption rate (0.05%), and extremely low dermal and
inhalation toxicity, these uses are expected to result in insignificant
risk, and will, therefore, not be included in the aggregate risk
assessment. Reference: ``Reregistration Eligibility Document:
Diflubenzuron,'' EPA, August 1997.
C. Cumulative Risk
Uniroyal Chemical Co. has considered the potential for cumulative
effects of diflubenzuron and other substances with a common mechanism
of toxicity. The mammalian toxicity of diflubenzuron is well defined.
We are not aware of any other pesticide product registered in the
United States that could be metabolized to p-chloroaniline. For this
reason, consideration of potential cumulative effects of residues from
pesticidal substances with a common mechanism of action as
diflubenzuron is not appropriate. Thus only the potential exposures to
diflubenzuron were considered in the total exposure assessment.
D. Safety Determination
1. U.S. population. Based on the available toxicology and exposure
data base for diflubenzuron, Uniroyal has determined that the total
possible non-occupational aggregate exposure from diflubenzuron would
occur from the dietary exposure route. Dietary exposure to the general
U.S. population from diflubenzuron was estimated at 0.000706 mg/kg/day.
Based on the 0.02 mg/kg/day RfD (reference dose) derived from the dog
chronic NOEL of 2 mg/kg/day and a 100-fold safety factor, this dietary
exposure is 3.5% of the RfD.
For PCA and CPU, Uniroyal has also determined that the total
possible non-occupational aggregate exposure would occur from the
dietary exposure route. Dietary exposure to the general U.S. population
from PCA/CPU was estimated as 0.000001 mg/kg/day. The risk from
diflubenzuron-derived PCA/CPU can be estimated using a linear
extrapolation of the dose-response from the rat chronic study conducted
by the National Toxicology Program in which rats were dosed via gavage
with p-chloroaniline hydrochloride 5 days/week for 103 weeks (NTP TR
351). EPA has determined the q1* as 0.059 by combining the incidences
of splenic sarcomas from both male and female rats.
Although EPA has assumed that CPU is also carcinogenic purportedly
based on its structural similarity to PCA, Uniroyal has indicated to
the Agency in previous correspondence that this assumption is not
warranted. It may be more appropriate to compare the carcinogenicity
potential of CPU to acetanilide, which is also a structural analog of
CPU, and for which no evidence of carcinogenicity has been demonstrated
possibly because the N-hydroxy metabolite is not formed in significant
amounts. Formation of the N-hydroxy metabolite of CPU is also remote.
Uniroyal has also argued that it is unlikely that significant
degradation of CPU to form PCA would occur, since based on the known
animal metabolism of phenylureas, only a small amount of aniline
derivatives are produced. The major metabolic pathway for the
phenylureas is ring hydroxylation and n-dealkylation, a process that
would maintain the integrity of the parent urea molecule. Therefore, it
would not be appropriate to combine CPU residues with PCA. However, for
this safety assessment we have conservatively estimated the risk from
dietary exposure to both PCA and CPU combined.
Using the q1* of 0.059 from the combined male and female incidence
of splenic tumors in rats, the risk to the general U.S. population from
dietary exposure to diflubenzuron-derived PCA/CPU is 8.7x10-
<SUP>8</SUP>.
2. Infants and children. The same assumptions as for the general
U.S. population were used for the dietary exposure risk determination
in infants and children. The dietary exposure of diflubenzuron was
calculated as 0.000799 mg/kg/day and 0.003461 mg/kg/day respectively
for nursing and non-nursing infants. These values are 4% and 17.3%
respectively of the RfD for diflubenzuron. The dietary exposure from
diflubenzuron in children 1-6 and 7-12 years old was determined as
0.001888 mg/kg/day and 0.001178 mg/kg/day, respectively. These values
are 9.4% and 5.9% of the RfD, respectively.
As previously discussed, the NOELs for maternal and developmental
toxicity in rats and rabbits were greater than
[[Page 9532]]
1,000 mg/kg/day, and the NOEL for reproductive toxicity was greater
than 5,000 mg/kg/day. Therefore, based on the completeness and
reliability of the toxicity data and the conservative exposure
assessment, Uniroyal concludes that there is reasonable certainty that
no harm will result in infants and children from aggregate exposure to
residues of diflubenzuron and its conversion products containing the p-
chloroaniline moiety.
E. Residues in the Raw Agricultural Commodity and Processed Food/Feed
1. Nature of residues in plants and livestock. The nature of the
residue in plants and livestock is adequately understood. In plants,
the metabolism of diflubenzuron was investigated in soybeans, oranges
and rice. The main component of residues in rice was CPU; levels of PCA
were negligible to non-detectible. The main component of the residues
in soybeans and oranges was the parent diflubenzuron (DFB). A
considerable portion of the residues were bound. DFB showed very
limited absorption and translocation in plants with most of the
residues remaining on the surface.
In livestock, goats treated for three days at about 1X (10 ppm
feeding level) the dietary burden of <SUP>C</SUP>14 DFB gave DFB
equivalent of <SUP>C</SUP>14 = 7-9 ppb in milk, 217-262 ppb in liver,
16-19 ppb in kidney, about 1 ppb in muscle, and about 4 ppb in fat.
Milk residues were mainly CPU and DFBAM. PCA was not detectable. Liver
residues were DFB, 2-hydroxy DFB, CPU, and DFBAM. Again, PCA was not
detected at this dose however, it was detected in studies conducted at
about 22X dose. Chickens were dosed with <SUP>C</SUP>14 DFB at 5 ppm
level for 1-28 days. Residues in tissues as DFB equivalent were highest
in liver and kidney. The main residues in tissues and eggs were DFB and
DFBA. Trace amount of PCA and its acetanilide were detected, but not
confirmed, in liver kidney and egg white.
2. Magnitude of residues and proposed tolerances. An adequate
number of separate residue trials have been conducted with
diflubenzuron on rice. Analyses of these trials show that the maximum
total residue for diflubenzuron and its conversion products PCA and CPU
will be at or below 0.01 ppm.
A tolerance has been requested for the combined residues of
diflubenzuron and metabolites convertible to p-chloroaniline expressed
as diflubenzuron on rice at 0.01 ppm. The proposed tolerance is
adequate to cover residues likely to be present from the use of
diflubenzuron on rice. Therefore, no special processing to reduce the
residues will be necessary.
The meat by-products tolerances are adequate to cover residues
resulting from the rice use. Uniroyal Chemical has submitted
calculations from a goat metabolism study which supports the 0.05 ppm
tolerance in meat by-products. Therefore, no increase in the meat by-
products tolerances should be necessary.
F. Practical Analytical Method
Practical analytical methods for detecting levels of DFB, CPU and
PCA, in or on food with a limit of detection that allows monitoring of
the residue at or above the level set in the tolerance was used to
determine residues in rice and its respective processed fractions.
Residues of the individual analytes are detectable and quantifiable
using three separate analytical methods. Residues of DFB are extracted
from rice with dichloromethane. Extracts are purified with deactivated
florisil. An aliquot of the extract is hydrolyzed with phosphoric acid
and the DFB is partitioned into hexane. The resulting extract is
derivatized in heptafluorobutyric anhydride (HFBA). Quantification of
DFB is accompanied by gas chromatography using an electron capture
detector.
The analytical method for quantitation of the 4-chlorophenylurea
requires ethyl acetate extraction of the residue from the matrix.
Column chromatography is utilized for clean-up of the extract
immediately prior to derivitization with HFBA. Derivatized extracts are
analyzed by gas chromatography equipped with an electron capture
detector.
The analysis for the determination of PCA residues in rice matrices
utilizes an internal standard method. Samples of matrix to be analyzed
are fortified with the internal standard. Residues of 12C-PCA and the
internal standard are subjected to acid and base hydrolysis. The final
extract is passed through florisil column for clean-up and derivatized
with HFBA in hexane. An aliquot of the derivatized extract is analyzed
by gas chromatography using a mass spectrometry detector in the
selective ion monitoring mode. Recovery of PCA is determined by the
combined peak areas for the two mass spectral ions obtained from the
derivatized 12C-PCA relative to the response factor derived from the
combined areas of the corresponding two mass spectral ions from the
internal standard.
G. List of All Pending Tolerances and Exemptions
A tolerance for diflubenzuron on range grass at 4.0 ppm is pending.
There are no exemptions from tolerance for diflubenzuron.
H. List International Tolerances (Code MRLs)
There are no Codex Alimentarius Commission maximum residue levels
for residues of diflubenzuron on rice. The Codex MRL on citrus is 1.0
mg/kg vs. 0.05 ppm for U.S. tolerance. The Codex MRL for mushrooms is
0.1 mg/kg vs. 0.2 ppm for U.S. tolerance. The Codex MRL for soybeans is
0.1 mg/kg/ vs. 0.05 ppm for the U.S. The Codex MRL is 1 mg/kg for
apples, Brussels sprouts, cabbage, pears, plums and tomatoes for which
there are no U.S. tolerances. The Codex MRL for meat, milk and eggs is
0.05 mg/kg/ which is the same as the established U.S. tolerances.
[FR Doc. 98-4812 Filed 2-24-98; 8:45 am]
BILLING CODE 6560-50-F