[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: [email protected].

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:
    [email protected]


    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