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Oxyfluorfen (Rohm & Haas). January 9, 1998. Pesticide Tolerance Petition. Federal Register.
http://www.epa.gov/fedrgstr/EPA-PEST/1998/January/Day-09/p557.htm
[Federal Register: January 9, 1998 (Volume 63, Number 6)]
[Notices]
[Page 1456-1464]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr09ja98-67]
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ENVIRONMENTAL PROTECTION AGENCY
[PF-786; FRL-5762-6]
Notice of Filing of Pesticide Petitions
AGENCY: Environmental Protection Agency (EPA).
[[Page 1457]]
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-786, must
be received on or before February 9, 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. 1132, 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. 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: The product manager listed in the
table below:
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Office location/
Product Manager telephone number Address
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Joanne Miller (PM 23)......... Rm. 237, CM #2, 703- 1921 Jefferson
305-6224, e-mail: Davis Hwy,
miller.joanne@epamail Arlington, VA
.epa.gov.
Marion Johnson (PM 10)........ Rm. 217, CM #2, 703- Do.
305-6788, e-mail:
johnson.marion@epamai
l.epa.gov.
Cynthia Giles-Parker (PM 22).. Rm. 229, CM #2, 703- Do.
305-7740, e-mail:
giles-
parker.cynthia@epamai
l.epa.gov.
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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-786] (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-786] 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: December 17, 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.
3. Rohm & Haas Company
PP 3F4229
EPA has received a pesticide petition (PP 3F4229) from Rohm & Haas
Company, Philadelphia, PA, 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 oxyfluorfen in or
on the raw agricultural commodities peanut meat, meal, vine, hay, crude
oil, soap stock, and refined oil at 0.05 ppm and peanut hulls at 0.10
ppm. The proposed analytical method involves extraction from the raw
agricultural commodity with methanol or acetonitrite. Extracts are
refluxed in presence of NaOH and Al to reduce and or hydrolyze residues
to 4-(2-chloro-4-(trifluoromethyl)-phenoxy)-2-ethoxybenzenenamine. The
derivatives are partitioned into hexane and heptafluorobutyryl
derivatives prepared. Following Florisel cleanup, residues are
determined by electron capture GLC. 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 and animal metabolism. The chemical identities of
potential plant residues resulting from the use of oxyfluorfen have
been elucidated. The principal residue in plants is parent oxyflurofen.
The chemical identities of potential animal residues resulting from
consumption of oxyfluorfen-treated crops have been elucidated. Parent
oxyfluorfen is the principal residue in animal tissues. Oxyfluorfen
residues do not transfer to milk (concentration <0.01 ppm at 10x dose).
Residues also do not appreciably transfer to cow muscle, liver and
kidney (highest level 0.011 ppm at 10x dose). Residues are present in
cow fat at low levels (less than 0.01 at 1x dose). Residues in eggs and
hen liver are 0.02 ppm or less on average at a 1x dose, and less than
0.01 ppm in muscle at the 1x dose. Residues approach 0.2 ppm in hen fat
at the 1x dose.
2. Analytical method. There is a practical analytical method for
detecting and measuring levels of oxyfluorfen in or on food with a
limit of detection that allows monitoring of food with residues at or
above the levels in these proposed tolerances. EPA has provided
information on this method to FDA. The method is available to anyone
who is interested in pesticide residue enforcement from: By mail,
Calvin Furlow, Public Response and Program Resources Branch, Field
Operations Division (7502C), Office of Pesticide Programs,
Environmental Protection Agency, 401 M St., SW., Washington, DC 20460.
Office location and telephone number: Crystal Mall #2, Rm. 1132, 1921
Jefferson Davis Highway, Arlington, Virginia, 703-305-5805.
3. Magnitude of the residues. Residue studies have been conducted
in accordance with the geographic distribution mandated by the EPA for
peanuts. Oxyfluorfen residues were not detectable in nutmeat [NDR <LOQ
= 0.01 mg/kg] or peanut hay [NDR<LOQ = 0.03 mg/kg]. Tolerances of 0.05
ppm in
[[Page 1462]]
nutmeat and hay are proposed based on these data. Residues were not
measured in processed fractions of peanuts and tolerances are not
proposed because residues are not likely to exceed the proposed 0.05
ppm tolerance level for nutmeat since the maximum theoretical
concentration factor for process fractions is 2x.
B. Toxicological Profile
1. Acute toxicity. Oxyfluorfen is practically nontoxic by the oral,
dermal, and respiratory routes of exposure, is nonirritating to the
skin and moderately irritating to the eye.
2. Genotoxicity. In vitro tests in salmonella and mouse lymphoma
cells have indicated the potential for genotoxicity. In vivo tests do
not show a potential for adverse chromosal effects.
3. Reproductive and developmental toxicity. Maternal and
developmental toxicity were noted at an oxyfluorfen dose of 183 mg/kg/
day (NOEL of 18 mg/kg/day) in rats and at a dose of 30 mg/kg/day (NOEL
of 10 mg/kg/day) in rabbits. Reductions in body weight of offspring and
histopathologic alteration of the kidneys of parents were observed with
a dose of oxyfluorfen of <difference>80 mg/kg/day (NOEL <difference>20
mg/kg/ day) in a rat 2-generation reproduction study.
4. Subchronic and chronic toxicity. Adverse effects on the liver
marked the LOEL in all three chronic toxicity studies with NOELs of
2.5, 2.0, and 0.3 mg/kg/day seen in the dog, rat, and mouse studies
respectively. A statistically significant positive dose-related trend
for liver adenomas and carcinomas was observed in the chronic mouse
study and oxyfluorfen is classified as a Group C chemical by EPA. A
reference dose of 0.003 mg/kg/day and a Q1<SUP>*</SUP> of 0.128 (mg/kg/
day) <SUP>-1</SUP> has been set by the Agency.
5. Animal metabolism. Animal metabolism studies have been conducted
on farm animals using laying hens and lactating goats and in a
laboratory animal (rat). These studies were reviewed and accepted by
the Agency. EPA has concluded that the metabolism of oxyfluorfen in
animals is adequately understood.
C. Aggregate Exposure
1. Food. To determine chronic (using the RfD) and cancer (using the
Q1<SUP>*</SUP> approach) risks, refined dietary exposure estimates
using percent of crop treated and anticipated residues were utilized
for registered uses of oxyfluorfen with established tolerances on the
following food and/or animal feed items: dates, figs, guava, loquats,
olives, papaya, persimmon, pomegranate, plantains, kiwi, cocoa butter,
coffee, artichokes, taro-roots and greens, garlic, shallots,
cauliflower, bok-choy, and other Chinese variety cole crops, dry beans,
crabapples, quince, blackberry, raspberry, Brazil nut, cashew,
chestnuts, hazelnuts, hickory nuts, macadamias, pecans, horseradish,
peppermint, spearmint, pistachio nuts, cotton, cherries, nectarines,
plums, prunes, almonds, walnuts, bananas, broccoli, cabbage, apricots,
nutmeat, milk, onions, soybeans, apples, pears, peaches, grapes, and
corn. Actual residues are expected to be quite low because the majority
of the use patterns direct sprays onto weeds or soil and away from the
crop. There are long preharvest intervals for sprays which are directly
applied to crops.
Acute dietary exposure (food only) was calculated using the TMRC
(worst case) assumptions.
2. Drinking water. The Agency has reviewed environmental fate data
which indicate that oxyfluorfen is persistent but nonmobile. There is
no established Maximum Concentration Level (MCL) for residues of
oxyfluorfen in drinking water. No health advisory levels for
oxyfluorfen in drinking water have been established. As noted in
``Pesticides in Groundwater Database'' EPA 734-12-92-001, September
1992, 188 wells were monitored in Texas in 1987 and 1988. No detectable
residues of oxyfluorfen were found in any of the samples.
While EPA has not yet pinpointed the appropriate bounding figure
for consumption of contaminated water, the ranges the Agency is
continuing to examine are all below the level that would cause
oxyfluorfen to exceed the RfD if the tolerance being considered in this
document were granted. In addition, chronic exposure to oxyfluorfen
residues resulting from potential water exposure would not increase the
total cancer risk so that it exceeds the Agency's level of concern. The
potential exposures associated with oxyfluorfen in water, even at the
higher levels the Agency is considering as a conservative upper bound
for RfD exposure considerations, would not prevent the Agency from
determining that there is a reasonable certainty of no harm if the
tolerance is granted.
Despite the potential for acute exposure to oxyfluorfen in drinking
water, it is not expected that the aggregate acute exposure will exceed
the Agency's level of concern if the tolerance being considered in this
document were granted. The potential acute term exposures associated
with oxyfluorfen in water, even at the higher levels the Agency is
considering as a conservative upper bound, would not prevent the Agency
from determining that there is a reasonable certainty of no harm if the
tolerance is granted.
3. Non-dietary exposure. Oxyfluorfen is registered for outdoor
residential use. Acceptable, reliable data are not currently available
with which to assess acute risk. However, based on the available
residential exposure data and the best professional judgment of
scientists who have worked with the available occupational exposure
data, 5% of the risk for outdoor residential uses is a reasonable,
protective default assumption for this pesticide. Chronic exposure to
oxyfluorfen residues resulting from potential outdoor residential
exposure would not increase the total chronic or cancer risks so that
they exceed the Agency's level of concern.
Theoretically, it is also possible that a residential, or other
non-dietary, exposure could be combined with the acute total dietary
exposure from food and water. However, the Agency does not believe that
aggregating multiple exposure to large amounts of pesticide residues in
the residential environment via multiple products and routes for a one-
day exposure is a reasonably probable event. It is highly unlikely
that, in one day, an individual would have multiple high-end exposures
to the same pesticide by treating their lawn and garden, treating their
house via crack and crevice application, swimming in a pool, and be
maximally exposed in the food and water consumed.
D. Cumulative Effects
EPA does not have, at this time, available data to determine
whether oxyfluorfen has a common mechanism of toxicity with other
substances or how to include this pesticide in a cumulative risk
assessment. Unlike other pesticides for which EPA has followed a
cumulative risk approach based on a common mechanism of toxicity,
oxyfluorfen does not appear to produce a toxic metabolite produced by
other substances. For the purposes of this tolerance action, therefore,
EPA has not assumed that oxyfluorfen has a common mechanism of toxicity
with other substances.
E. Endocrine Effects
The toxicity studies required by EPA for the registration of
pesticides measure numerous endpoints with sufficient sensitivity to
detect potential endocrine-modulating activity. No effects have been
identified in subchronic, chronic, reproductive, or developmental
toxicity studies to indicate any endocrine-modulating activity by
oxyfluorfen.
[[Page 1463]]
More importantly, the multi-generation reproduction study in rodents is
a complex study design which measures a broad range of endpoints in the
reproductive system and in developing offspring that are sensitive to
alterations by chemical agents. Oxyfluorfen has been tested in two
separate multi-generation studies and each time the results
demonstrated that oxyfluorfen is not a reproductive toxin.
F. Safety Determination
1. U.S. population-- i. Chronic RfD and cancer risk. Using the
refined dietary exposure assumptions described above and taking into
account the completeness and reliability of the toxicity data, it is
concluded that aggregate dietary exposure (food only) to oxyfluorfen
will utilize 0.04% of the RfD for the general United States population.
EPA has no concern generally for exposures below 100% of the RfD
because the RfD represents the level at or below which daily aggregate
dietary exposure over a lifetime will not pose appreciable risks to
human health. Despite the potential for exposure to oxyfluorfen in
drinking water and from the 5% default-level contribution from non-
dietary, nonoccupational exposure, it is not expected the aggregate
exposure will exceed 100% of the RfD. As noted above, oxyfluorfen has
been classified as a Group C chemical by the Agency based on liver
adenomas and carcinomas in the 20-month mouse feeding study. The Agency
recommends using the Q1<SUP>*</SUP> approach to assess cancer risk. A
value of 0.067 (mg/kg/day)<SUP>-1</SUP> is recommended.
The refined dietary assumptions for existing oxyfluorfen tolerances
plus those proposed for peanuts result in an Anticipated Residue
Contribution (ARC) that is equivalent to a risk of 8.0 x
10<SUP>-8</SUP> (food only). Actual residues are expected to be quite
low because the majority of the use patterns direct sprays onto weeds
and away from the crop and there are long preharvest intervals for
sprays which are directly applied to crops. Environmental fate data
indicate that oxyfluorfen strongly adheres to soil, does not leach into
groundwater and has not been detected in sampled groundwater. Based on
this information, occurrence of oxyfluorfen in drinking water is
unlikely. Outdoor residential uses of oxyfluorfen are limited and
exposure is expected to be low. Oxyfluorfen is toxic to lawn grasses
and certain ornamental plants, and use is generally limited to spot
treatments for nonselective weed control. Chronic exposure to
oxyfluorfen residues resulting from potential residential and/or water
exposure would not increase the total cancer risk so that it exceeds
the Agency's level of concern. There is a reasonable certainty that no
harm will result from chronic aggregate exposure to oxyfluorfen
residues.
ii. Acute risk. The acute dietary exposure endpoint of concern for
oxyfluorfen is fused sternebrae in developing pups which was observed
in the rabbit developmental study. The population subgroup of concern
is females 13+ years old (women of childbearing age). For this
subgroup, the calculated MOE at the high end exposure is greater than
5,000. The Agency considers dietary (food) MOEs of greater than 100 to
be acceptable for oxyfluorfen. Acute dietary exposure (food only) was
calculated using the TMRC (worst case) assumptions.
In the absence of data for drinking water exposure, the ranges of
exposure being considered by the Agency for consumption of contaminated
water will be reserved for drinking water. The aggregate MOE level of
concern for dietary plus the addition of upperbound estimates for
drinking water is not likely to raise the MOE level of concern above
150. Despite the potential for acute exposure to oxyfluorfen in
drinking water, it is not expected that the aggregate exposure will
exceed the Agency's level of concern if the tolerance being considered
in this document were granted. It is therefore concluded that the
potential acute exposure associated with oxyfluorfen in water, even at
the higher levels the Agency is considering as a conservative upper
bound, would not prevent the Agency from determining that there is a
reasonable certainty of no harm if the tolerance is granted.
2. Infants and Children. The toxicology database is complete for
oxyfluorfen relative to prenatal and postnatal toxicity. In the
developmental toxicity study in rabbits, at the maternally toxic dose
of 30 mg/kg/day, there were developmental anomalies (fused sternebrae)
in the fetuses which demonstrated that prenatal toxicity should be
evaluated by an acute dietary risk estimate. The acute dietary MOE for
pregnant women 13+ years old is greater than 5,000 based on a
developmental NOEL of 10 mg/kg/day. This MOE is much higher than the
minimal acceptable MOE (100 for dietary-food only) and suggests that
prenatal developmental risks to infants and children from exposure to
oxyfluorfen dietary residues is not a concern. Additionally, the rabbit
developmental NOEL of 10 mg/kg/day is 33 times greater than the NOEL of
0.3 mg/kg/day used to calculate the RfD. In the developmental toxicity
study in rats, both the developmental and maternal NOEL and LOEL of 18
and 183 mg/kg/day, respectively, occurred at the same dose levels and
demonstrates that there is no special sensitivity in infants and
children exposed to oxyfluorfen. Although the developmental findings in
the rat were severe effects, the developmental NOEL of 18 mg/kg/day is
greater than the rabbit developmental NOEL of 10 mg/kg/day used to
calculate acute dietary MOEs. Therefore, the acute dietary risk
estimates calculated from the rabbit developmental NOEL are lower than
acute dietary MOEs which could be calculated for the more severe
effects occurring in rats above the NOEL of 18 mg/kg/day. By basing the
acute dietary MOEs on the NOEL in the most sensitive species (rabbit),
pregnant women are protected against both types of prenatal toxicity
effects as seen in the rat and rabbit developmental toxicity studies.
Therefore, there are no significant prenatal toxicity concerns for
infants and children due to the high MOE for pregnant women 13+ years
old. In the 2-generation reproductive toxicity study in rats used to
assess the postnatal toxicity potential of infants and children, the
NOEL and LOEL of 20 mg/kg/day and 80 mg/kg/day, respectively, for
developmental/reproductive and systemic toxicity demonstrated that
there are no pup toxicity effects in the absence of parental toxicity
(NOEL and LOEL are the same for pups and parental animals). Therefore,
there are no special postnatal sensitivities in infants and children
which can be attributed to the findings of the 2-generation
reproductive toxicity study in rats. Additionally, the developmental/
reproductive NOEL of 20/mg/kg/day [which is the NOEL for decreased
litter size at birth as well as decreased pup body weight] and the
parental systemic NOEL of 20 mg/kg/day is 66 times greater than the
NOEL of 0.3 mg/kg/day used to calculate the RfD.
Based on the above, EPA concludes that reliable data support use of
the standard hundredfold margin of exposure/uncertainty factor and that
an additional margin/factor is not needed to protect the safety of
infants and children.
i. Chronic risk. Using the refined exposure assumptions described
above and taking into account the completeness and reliability of the
toxicity data, it is concluded that aggregate dietary exposure to
oxyfluorfen will utilize 0.05% of the RfD for infants and 0.08% of the
RfD for children. EPA generally has no concern for exposures below 100%
of the RfD because the RfD represents the level at
[[Page 1464]]
or below which daily aggregate dietary exposure over a lifetime will
not pose appreciable risks to human health. Despite the potential for
exposure to oxyfluorfen in drinking water and from non-dietary,
nonoccupational exposure, the chronic aggregate exposure is not
expected to exceed 100% of the RfD. There is a reasonable certainty
that no harm will result to infants and children from chronic aggregate
exposure to oxyfluorfen residues.
ii. Acute risk. As mentioned above, the acute dietary exposure
endpoint of concern for oxyfluorfen is fused sternebrae in developing
pups which was observed in the rabbit developmental study. The
population subgroup of concern is females 13+ years old (women of
childbearing age). For this subgroup, the calculated MOE at the high
end exposure is greater than 5,000. The Agency considers dietary (food)
MOEs of greater than 100 to be acceptable for oxyfluorfen. Acute
dietary exposure (food only) was calculated using the TMRC (worst case)
assumptions.
In the absence of data for drinking water exposure, the ranges of
exposure being considered by the Agency for consumption of contaminated
water will be reserved for drinking water. Based on the ranges under
consideration, the aggregate MOE level of concern for dietary plus the
addition of drinking water is not likely to raise the MOE above the
Agency's level of concern. The large MOE calculated for this use of
oxyfluorfen provides assurance that there is a reasonable certainty of
no harm for infants and children.
G. International Tolerances
There are no Codex Alimentarius Commission (CODEX) maximum residue
levels (MRL's) established for residue of oxyfluorfen in or on raw
agricultural commodities. (PM 23)
[FR Doc. 98-557 Filed 1-8-98; 8:45 am]
BILLING CODE 6560-50-F