[Federal Register Volume 62, Number 187 (Friday, September 26, 1997)]
[Notices]
[Pages 50610-50613]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-25656]
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ENVIRONMENTAL PROTECTION AGENCY
[PF-760; FRL-5740-2]
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-760, must
be received on or before October 27, 1997.
ADDRESSES: By mail submit written comments to: Public Information and
Records Integrity Branch (7506C), 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. 1132, CM #2, 1921 Jefferson Davis Highway, Arlington, VA.
Comments and data may also be submitted electronically by following
the instructions under ``SUPPLEMENTARY INFORMATION.'' No confidential
business information should be submitted through e-mail.
Information submitted as a comment concerning this document may be
claimed confidential by marking any part or all of that information as
``Confidential Business Information'' (CBI). CBI should not be
submitted through e-mail. Information marked as CBI will not be
disclosed except in accordance with procedures set forth in 40 CFR part
2. A copy of the comment that does not contain CBI must be submitted
for inclusion in the public record. Information not marked confidential
may be disclosed publicly by EPA without prior notice. All written
comments will be available for public inspection in Rm. 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: Indira Gairola, Registration
Division (7505W), Office of Pesticide Programs, Environmental
Protection Agency, 401 M St., SW., Washington, DC 20460. Office
location and telephone number: Rm. W-57, 4th floor, CS #1, Westfield
Building North Tower, 2800 Crystal Drive, Arlington, VA 22202, 703-308-
8371, e-mail: gairola.indira@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-760] (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 file format or ASCII
file format. All comments and data in electronic form must be
identified by the docket number [PF-760] 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: September 16, 1997.
James Jones,
Acting Director, Registration Division, Office of Pesticide Programs.
Summaries of Petitions
Petitioner summaries of the pesticide petitions are printed below
as required 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.
AgrEvo
PP 7F4850
EPA has received a pesticide petition (PP 7F4850) from AgrEvo,
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 herbicide safener Mefenpyr-
diethyl (HOE 107892) on wheat and barley
[[Page 50611]]
commodities. The proposed analytical method involves homogenization,
filtration, partition and cleanup with analysis by high performance
liquid chromatography using UV detection. EPA has determined that the
petition contains data or information regarding the elements set forth
in section 408(d)(2) of the FFDCA; however, EPA has not fully evaluated
the sufficiency of the submitted data at this time or whether the data
supports granting of the petition. Additional data may be needed before
EPA rules on the petition.
A. Residue Chemistry
1. Plant metabolism. The fate of mefenpyr-diethyl has been
determined in young barley plants and the nature of the residue is
understood. Residues of concern are mefenpyr-diethyl and its 2,4-
dichlorophenyl-pyrazoline metabolites, all of which are detected and
quantified by the analytical method described above.
Residue trials have been conducted in the United States in 1995 and
1996. When applied as a single application at a rate of 0.089 lb. of
safener per acre, combined residues in wheat or barley grain did not
exceed 0.04 ppm. In wheat or barley straw, combined residues did not
exceed 0.67 ppm, and in wheat or barley hay combined residues did not
exceed 0.35 ppm. In these same trials, combined residues did not exceed
0.55 ppm in wheat forage. Thus, the proposed tolerances of 0.05 ppm in
barley and wheat grain, 0.75 ppm in wheat straw and forage, 0.5 ppm in
wheat and barley hay, and 1.0 ppm in barley straw are adequate.
2. Analytical method. A practical analytical method utilizing gas
chromatography and a mass selective detector is available for detecting
and measuring levels of mefenpyr-diethyl and its 2,4-dichlorophenyl-
pyrazoline containing metabolites in wheat grain and straw. The limit
of quantitation (LOQ) is 0.01 mg/kg (ppm) in wheat and barley grain,
0.05 mg/kg (ppm) in wheat and barley straw and wheat hay, and 0.1 ppm
in wheat forage.
3. Magnitude of residues. The fate of mefenpyr-diethyl has been
determined in young barley plants and the nature of the residue is
understood. Residues of concern are mefenpyr-diethyl and its 2,4-
dichlorophenyl-pyrazoline metabolites, all of which are detected and
quantified by the analytical method described above.
Residue trials have been conducted in the United States in 1995 and
1996. When applied as a single application at a rate of 0.089 lb. of
safener per acre, combined residues in wheat or barley grain did not
exceed 0.04 ppm. In wheat or barley straw, combined residues did not
exceed 0.67 ppm, and in wheat or barley hay combined residues did not
exceed 0.35 ppm. In these same trials, combined residues did not exceed
0.55 ppm in wheat forage. Thus, the proposed tolerances of 0.05 ppm in
barley and wheat grain, 0.75 ppm in wheat straw and forage, 0.5 ppm in
wheat and barley hay, and 1.0 ppm in barley straw are adequate.
The metabolism of mefenpyr-diethyl in poultry is adequately
understood. Laying hens were fed the compound at a level approximately
5-times the worst case dietary burden for 14-days. Low levels of
residues of mefenpyr-diethyl were detected in fat, and low levels of
residues of mefenpyr-diethyl and its 2,4-dichlorophenyl-pyrazoline
containing metabolites were detected in liver and eggs.
The metabolism of mefenpyr-diethyl in ruminants is also adequately
understood. A lactating goat was dosed with the compound at a level
approximately 56-times the worst case dietary burden for 7-days. Low
levels of residues of mefenpyr-diethyl and/or its 2,4-dichlorophenyl-
pyrazoline containing metabolites were detected in liver and eggs.
B. Toxicological Profile
1. Acute toxicity. The acute oral LD50 of mefenpyr-
diethyl was greater than 5,000 mg/kg in both rats and mice. The acute
rat dermal LD50 was greater than 4,000 mg/kg, and the acute
rat inhalation LC50 (4-hour) was greater than 1.32 mg/l.
Mefenpyr-diethyl was slightly irritating to the eyes of rabbits. It was
not irritating to rabbit skin in a standard dermal irritation study but
was a weak dermal sensitizer in a guinea pig maximization study.
Evidence of photoirritation, but no photosensitization, was observed in
other studies with guinea pigs. Based on these results, mefenpyr-
diethyl is expected to be classified as TOXICITY CATEGORY IV for acute
oral toxicity and skin irritation, and TOXICITY CATEGORY III for acute
dermal and inhalation toxicity, and eye irritation.
2. Genotoxicty. No evidence of genotoxicity was observed in a
battery of studies including Salmonella and E. coli bacterial gene
mutation assays, an HGPRT gene mutation assay in Chinese hamster cells,
a mouse micronucleus assay, an in vitro chromosome aberration assay,
and an in vitro unscheduled DNA synthesis assay.
3. Reproductive and developmental toxicity. Two rat developmental
toxicity studies have been conducted with mefenpyr-diethyl. In the
first study, Wistar rats were administered mefenpyr-diethyl by gavage
at dose levels of 0 and 1,000 mg/kg body weight/day on gestation days 7
to 16. The fetuses were delivered by cesarean section on gestation day
21 and evaluated for external, visceral and/or skeletal anomalies. No
maternal or developmental effects were noted in this study. Thus, the
NOEL for maternal and developmental effects was considered to be 1,000
mg/kg bodyweight. In the second study, Wistar rats were again
administered mefenpyr-diethyl by gavage at dose levels of 0 and 1,000
mg/kg body weight/day on gestation days 7 to 16, but the dams were then
allowed to deliver normally and the offspring were evaluated for up to
44-days post-partum. No maternal effects were observed in this study.
There was a marginal decrease in the body weight of the offspring at
birth and during lactation but no other changes in physical,
functional, or behavioral endpoints were observed.
In a rabbit developmental toxicity study, mefenpyr-diethyl was
administered by gavage to Himalayan rabbits at dose levels of 0, 40,
100, and 250 mg/kg body weight/day on gestation days 6 to 18. The
highest dose tested was toxic to both dams and embryos, as evidenced by
a decreased food and water consumption, decreased maternal body
weights, abortions, and increased incidences of intrauterine death. No
morphological effects on the offspring were noted. The NOEL for
maternal and embryonic toxicity was considered to be 100 mg/kg body
weight.
A 2-generation reproduction study was conducted in Wistar rats fed
diet containing mefenpyr-diethyl at dietary concentrations of 0, 200,
1,000, and 5,000 ppm for 70-days then continuously through successive
generations. Effects observed at 5,000 ppm consisted of decreased food
consumption, decreased body weight gain, increased spleen weights and
increased splenic hematopoiesis in the parental animals, and decreased
body weights in the pups during lactation. No effects on reproductive
parameters were noted. Thus, the overall study NOEL for both parents
and the progeny was considered to be 1,000 ppm, equivalent to a mean
daily substance intake of 75 and 99 mg/kg bodyweight for the males and
females, respectively.
4. Subchronic toxicity. In a 90-day feeding study, mefenpyr-diethyl
was administered to Wistar rats at concentrations of 0, 100, 500,
2,500, and 7,500 ppm in the diet. Based on slight reduction in body
weight at 7,500 ppm and minimal to slight anemia at 2,500 and 7,500
ppm, the NOEL was considered to be 500 ppm, equivalent to
[[Page 50612]]
a mean daily test substance intake of 42 mg/kg body weight.
In a 90-day feeding study in beagle dogs, mefenpyr-diethyl was
administered in the diet at concentrations of 0, 400, 2,000, and 10,000
ppm. Effects observed at 10,000 ppm included decreased food consumption
and body weight gain, increased liver weights, anemia, and alterations
in several clinical chemistry parameters. There were no
histopathological changes. Increased liver weight and increases in two
serum enzymes were noted at 2,000 ppm. Thus, the NOEL was considered to
be 400 ppm, equivalent to a mean daily test substance intake of 15 mg/
kg body weight.
In a 90-day feeding study in NMRI mice, mefenpyr-diethyl was
administered in the diet at concentrations of 0, 100, 500, 2,500, and
7,500 ppm. Effects noted at 7,500 ppm included decreased food
consumption and body weight gain, slight anemia, alterations in several
hematology and clinical chemistry parameters, slightly increased spleen
weights, and markedly increased liver weights. Histopathological
evaluation revealed hepatocellular hypertrophy in the liver, and
increased hemosiderin deposits and compensatory hematopoiesis in the
spleen. Effects noted at 2,500 ppm included decreased weight gain,
minor alterations in several clinical pathology parameters, slight
increases in liver weights, and hepatocellular hypertrophy. The NOEL
for this study was considered to be 500 ppm, equivalent to a mean daily
substance intake of 89 mg/kg body weight.
In a subchronic dermal toxicity study, mefenpyr-diethyl was applied
to Wistar rats at dose levels of 0, 100, 300, and 1,000 mg/kg body
weight for six hours per day, 5-days a week, for a total of 21-days
over a period of 30-days. Based on slight anemia observed among the
females at 1,000 mg/kg body weight, the NOEL was considered to be 300
mg/kg bodyweight.
5. Chronic toxicity. A 2-year feeding chronic toxicity/
carcinogenicity study was conducted in Wistar rats with mefenpyr-
diethyl at dietary concentrations of 0, 40, 200, 1,000, and 5,000 ppm.
No evidence of carcinogenicity was observed in this study. Based on
slight reductions in female body weights and slight anemia in both
sexes at 5,000 ppm, the NOEL was considered to be 1,000 ppm, equivalent
to a mean daily substance intake of 48 and 60 mg/kg bodyweight in males
and females, respectively.
A 2-year feeding chronic toxicity/carcinogenicity study was
conducted in NMRI mice with mefenpyr-diethyl at dietary concentrations
of 0, 20, 100, 500, and 2,500 ppm. No evidence of carcinogenicity was
observed in this study. Slight but consistently reduced body weights
and slight increases in liver weight were noted in male mice at 2,500
ppm. Hepatocellular hypertrophy was noted in both sexes at 2,500 ppm,
in male mice only at 500 ppm, and in a few males at 100 ppm.
Hematology, serum biochemistry and urinalysis parameters were
unaffected. Because of the low incidence and severity of the
hepatocellular hypertrophy at 100 ppm, the NOAEL for this study was
considered to be 500 ppm, equivalent to a mean daily intake of 71 mg/kg
body weight.
A 1-year feeding study was conducted in beagle dogs with mefenpyr-
diethyl at dietary concentrations of 0, 60, 300, 1,500, and 7,500 ppm.
There was a slight decrease in food consumption in males at 7,500 ppm,
but body weights were unaffected. Other effects at this dose level
consisted of slight anemia, a slight increase in platelet count,
alterations in several clinical chemistry parameters, moderately to
markedly increased liver weights, slightly increased thyroid weights,
slightly decreased prostate weights, and minimal intrahepatic
cholestasis. The NOEL for this study was considered to be 1,500 ppm,
equivalent to a mean daily test substance intake of 55 mg/kg body
weight.
6. Animal metabolism. The metabolism of mefenpyr-diethyl in poultry
is adequately understood. Laying hens were fed the compound at a level
approximately 5-times the worst case dietary burden for 14-days. Low
levels of residues of mefenpyr-diethyl were detected in fat, and low
levels of residues of mefenpyr-diethyl and its 2,4-dichlorophenyl-
pyrazoline containing metabolites were detected in liver and eggs.
The metabolism of mefenpyr-diethyl in ruminants is also adequately
understood. A lactating goat was dosed with the compound at a level
approximately 56-times the worst case dietary burden for 7-days. Low
levels of residues of mefenpyr-diethyl and/or its 2,4-dichlorophenyl-
pyrazoline containing metabolites were detected in kidney, liver, fat,
and milk.
Based on the results observed in these metabolism studies,
secondary residues in animal commodities are not expected to be of
concern in terms of dietary risk to consumers.
C. Aggregate Exposure
Mefenpyr-diethyl is intended for use on agricultural crops as a
herbicide safening agent. As such, non-occupational exposures to
mefenpyr-diethyl would be limited to potential exposures via residues
in food or water. There are no acute toxicity concerns with mefenpyr-
diethyl. Therefore, only chronic exposures are being addressed here.
Dietary exposure--1. Food. Potential dietary exposures from food
under the proposed tolerances were estimated using the Exposure 1
software system (TAS, Inc.) and the 1977-78 USDA consumption data. For
the purposes of this risk assessment, AgrEvo USA Company has made the
overly conservative assumption that 100% of all wheat and barley
commodities will contain residues of mefenpyr-diethyl and that all of
those residues will be at the proposed tolerance level. Further,
default concentration factors are assumed for processed wheat and
barley commodities. Thus, this estimate should result in a gross
overestimation of actual human exposure. allowing administration.
Metabolite profiles were similar following oral and dermal exposures,
with the route of metabolism being hydrolysis of the two carboxylic
acid ester groups, and decarboxylation of one of the carboxylic acid
groups resulting in the aromatization of the heterocyclic ring.
2. Drinking water. The potential for mefenpyr-diethyl to leach into
groundwater has been assessed in various laboratory studies. These
experiments clearly demonstrate that mefenpyr-diethyl is rapidly
degraded in the environment, chiefly via metabolism in biologically
active soils. Aerobic degradation half-lives of 3-days or less were
observed under a wide range of experimental conditions. Clear
degradation of metabolites was also observed, with soil photolysis
accelerating the process. Mefenpyr-diethyl was stable to hydrolysis
under acid conditions, but was rapidly degraded at mildly alkaline pH
vales. Rapid photodegradation was observed under those aqueous
conditions where mefenpyr-diethyl is stable to hydrolysis. The compound
sorbed readily to soil organic matter, therefore, leaching is not of
concern. Based on these environmental fate data and the anticipated
conditions of use, the potential for movement of mefenpyr-diethyl is
considered to be low. As such, the potential contribution of any
residues of the compound in water to the total dietary intake of
mefenpyr-diethyl will be negligible.
[[Page 50613]]
D. Cumulative Effects
The potential for mefenpyr-diethyl to leach into groundwater has
been assessed in various laboratory studies. These experiments clearly
demonstrate that mefenpyr-diethyl is rapidly degraded in the
environment, chiefly via metabolism in biologically active soils.
Aerobic degradation half-lives of 3- days or less were observed under a
wide range of experimental conditions. Clear degradation of metabolites
was also observed, with soil photolysis accelerating the process.
Mefenpyr-diethyl was stable to hydrolysis under acid conditions, but
was rapidly degraded at mildly alkaline pH vales. Rapid
photodegradation was observed under those aqueous conditions where
mefenpyr-diethyl is stable to hydrolysis. The compound sorbed readily
to soil organic matter, therefore leaching is not of concern. Based on
these environmental fate data and the anticipated conditions of use,
the potential for movement of mefenpyr-diethyl is considered to be low.
As such, the potential contribution of any residues of the compound in
water to the total dietary intake of mefenpyr-diethyl will be
negligible.
E. Safety Determination
1. U.S. population. A Reference Dose value (RfD) of 0.48 mg/kg body
weight/day is appropriate for chronic dietary risk assessments of
mefenpyr-diethyl. This RfD is based on the 2-year rat chronic toxicity
study in which the NOEL was 1,000 ppm, equivalent to 48 mg/kg body
weight for males, and a 100-fold safety factor to account for
interspecies extrapolation and intraspecies variation.
Under the conservative (worst-case) dietary exposure assumption
described above in paragraph D.1., chronic dietary exposures will
utilize only 0.11% of the RfD for the general U.S. population. There is
generally no concern for exposures below 100% of the RfD since it
represents the level at or below which no appreciable risks to human
health is posed. Thus, there is reasonable certainty that no harm will
result to the U.S. population in general from aggregate exposure to
mefenpyr-diethyl residues.
2. Infants and children. Data from rat and rabbit development
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.
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. However, the
toxicology database for mefenpyr-diethyl regarding potential pre- and
post-natal effects in offspring is complete according to existing
Agency data requirements and does not indicate any particular
developmental or reproductive concerns. No reproductive effects were
noted in any of the studies and the NOEL's for the parents and
offspring were the same in three of the four studies. A marginal
decrease in pup weights was noted at a non-maternally toxic dose level
in the second rat developmental toxicity study, but only at a dose
level of 1,000 mg/kg/day. Thus, there does not appear to be any
significant difference in sensitivity to mefenpyr-diethyl between
adults and offspring. Furthermore, the proposed RfD of 0.48 mg/kg/day,
which is based on a 48 mg/kg/day NOEL from the 2-year rat feeding
study, already provides for a safety factor of 208 relative to the 100
mg/kg/day developmental NOEL from the rabbit developmental toxicity
study. Thus, the RfD of 0.48 mg/kg/day is considered 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 mefenpyr-diethyl is expected to utilize 0.25% of the
reference dose in the population subgroups children 1-6 years old and
0.18% of the reference dose in the population subgroup children 7-12
years old. These numbers would, in all likelihood, be significantly
lower if an adjustment for actual percent of crop treated was
considered.
F. International Tolerances
Italy has established an MRL (maximum residue limit) of 0.05 ppm in
wheat grain for residues of mefenpyr-diethyl and metabolites.
[FR Doc. 97-25656 Filed 9-25-97; 8:45 am]
BILLING CODE 6560-50-F
