[Federal Register Volume 62, Number 70 (Friday, April 11, 1997)]
[Rules and Regulations]
[Pages 17723-17730]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-9231]
[[Page 17723]]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Parts 180, 185, and 186
[OPP-300469; FRL-5598-6]
Glyphosate; Pesticide Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This rule establishes permanent tolerances for residues of the
herbicide glyphosate [N-(phosphonomethyl)glycine] in or on the raw
agricultural commodities (RACs) corn, field, grain; corn, field,
stover; corn, field, forage; aspirated grain fractions; sorghum, grain;
sorghum, grain, stover; and oats. The residues from the treatment of
field corn include residues in or on field corn varieties which have
been genetically modified to be tolerant of glyphosate. Monsanto
Company submitted petitions to EPA under the Federal Food, Drug, and
Cosmetic Act (FFDCA) as amended by the Food Quality Protection Act of
1996 (Pub L. 104-179) requesting the tolerances.
EFFECTIVE DATES: These regulations become effective April 11, 1997.
Written objections must be submitted by June 10, 1997.
ADDRESSES: Written objection and hearing requests, identified by the
docket control number, [OPP-300469; PP 8F3672, 8F3673, 5F4555, 6E4645],
may be submitted to: Hearing Clerk (1900), Environmental Protection
Agency, Rm. M3708, 401 M St., SW., Washington, DC 20460. Fees
accompanying objections shall be labeled ``Tolerance Petition Fees''
and forwarded to: EPA Headquarters Accounting Operations Branch, OPP
(Tolerance Fees), P.O. Box 360277M, Pittsburgh, PA 15251. A copy of any
objections and hearing request filed with the Hearing Clerk should be
identified by the docket control number and submitted to: Public
Response and Program Resources Branch, Field Operations Division
(7506C), Office of Pesticide Programs, Environmental Protection Agency,
401 M St., SW., Washington, DC 20460. In person, bring a copy of
objections and hearing requests to: Rm. 1132, CM#2, 1921 Jefferson
Davis Highway., Arlington, VA 22202.
A copy of objections and hearing requests filed with the Hearing
Clerk may also be submitted electronically by sending electronic mail
(e-mail) to: oppdocket@epamail.epa.gov. Copies of objections and
hearing requests must be submitted as an ASCII file avoiding the use of
special characters and any form of encryption. Copies of objections and
hearing requests will also be accepted on disks in WordPerfect in 5.1
file format or ASCII file format. All copies of objections and hearing
requests in electronic form must be identified by the docket number
[OPP-300469; PP 8F3672, 8F3673, 5F4555, 6E4645]. No Confidential
Business Information (CBI) should be submitted through e-mail.
Electronic copies of objections and hearing requests on this rule may
be filed online at many Federal Depository Libraries. Additional
information on electronic submission can be found in Unit XIII. of this
document.
FOR FURTHER INFORMATION CONTACT: By mail, Philip V. Errico, Product
Manager, Registration Division (H7505C), Office of Pesticide Programs,
Environmental Protection Agency, 401 M St., SW., Washington, DC 20460.
Office location, telephone number and e-mail address: Rm. 241, CM #2,
1921 Jefferson Davis Highway., Arlington, VA, (703)-305-6027; e-mail:
errico.philip@epamail.epa.gov.
SUPPLEMENTARY INFORMATION: In the Federal Register of December 24, 1996
(61 FR 67804)(FRL-5576-6), EPA issued a Notice of Filing amending
petitions PP 8F3672, 8F3673, 5F4555, 6E4645 to bring the petitions into
conformity with the Food Quality Protection Act (FQPA of 1996). The
notice contained a summary of the petitions prepared by the petitioner
and the summary contained conclusions and arguments to support its
conclusion that the petitions complied with FPQA. In that notice
Monsanto Company, 700 14th Street, NW., Suite 1100, Washington, DC
20005 proposed amending 40 CFR 180.364 by establishing a regulation to
permit residues of the herbicide glyphosate (N-
(phosphonomethyl)glycine) resulting from the application of the
isopropylamine salt and/or the monoammonium salt of glyphosate in or on
the raw agricultural commodities (RACs) field corn grain at 1.0 ppm;
field corn forage at 1.0 ppm; field corn fodder at 100 ppm; aspirated
grain fractions at 200 ppm; grain sorghum at 15 ppm; grain sorghum
fodder at 40 ppm; and oats at 20 ppm. The notice stated that PP 5F4555
specifically related to field corn which had been genetically modified
to be tolerant to glyphosate.
The Agency received one comment opposing the tolerances. The
commentor`s objection was based on concerns of (1) Enhanced exposure of
the public to glyphosate and other ingredients of the Roundup
formulations, (2) greater use of Roundup/glyphosate which will result
in adverse effects to the environment and human health, and (3)
exposure of the public to Roundup from consumption of the corn or the
animal product from animals fed corn. EPA`s response to this comment is
provided below.
The Agency determined that the terminology for field corn grain,
field corn, forage; field corn, fodder; aspirated grain fractions;
grain sorghum, and grain sorghum, fodder; should be corrected to read
corn, field, grain; corn, field, stover; corn, field, forage; aspirated
grain fractions; sorghum, grain; and sorghum, grain, stover; The
subject regulation is therefore amended accordingly.
The data submitted in the petitions and other relevant material
have been evaluated. The glyphosate toxicological data listed below
were considered in support of these tolerances.
I. Toxicological Profile
1. Several acute toxicology studies placing technical-grade
glyphosate in Toxicity Category III and Toxicity Category IV. Technical
glyphosate is not a dermal sensitizer.
2. A 1-year feeding study with dogs fed dosage levels of 0, 20,
100, and 500 milligrams/kilogram/day (mg/kg/day) with a no-observable-
effect level (NOEL) of 500 mg/kg/day.
3. A 2-year carcinogenicity study in mice fed dosage levels of 0,
150, 750, and 4,500 mg/kg/day with no carcinogenic effect at the
highest dose tested (HDT) of 4,500 mg/kg/day.
4. A chronic feeding/carcinogenicity study in male and female rats
fed dosage levels of 0, 3, 10, and 31 mg/kg/day (males) and 0, 3, 11,
or 34 mg/kg/day (females) with no carcinogenic effects observed under
the conditions of the study at dose levels up to and including 31 mg/
kg/day HDT (males) and 34 mg/kg/day HDT (females) and a systemic NOEL
of 31 mg/kg/day HDT (males) and 34 mg/kg/day HDT (females). Because a
maximum tolerated dose (MTD) was not reached, this study was classified
as supplemental for carcinogenicity.
5. A chronic feeding/carcinogenicity study in male and female rats
fed dosage levels of 0, 89, 362, and 940 mg/kg/day (males) and 1, 113,
457, and 1,183 mg/kg/day (females) with no carcinogenic effects noted
under the conditions of the study at dose levels up to and including
940/1,183 mg/kg/day (males/females) HDT and a systemic NOEL of 362 mg/
kg/day (males) based on an increased incidence of cataracts and lens
abnormalities, decreased urinary pH, increased liver weight and
increased liver weight/brain ratio (relative liver
[[Page 17724]]
weight) at 940 mg/kg/day (males) HDT and 457 mg/kg/day (females) based
on decreased body weight gain 1,183 mg/kg/day (females) HDT.
6. A developmental toxicity study in rats given doses of 0, 300,
1,000, and 3,500 mg/kg/day with a developmental NOEL of 1,000 mg/kg/day
based on an increase in number of litters and fetuses with unossified
sternebrae, and decrease in fetal body weight at 3,500 mg/kg/day, and a
maternal NOEL of 1,000 mg/kg/day based on decrease in body weight gain,
diarrhea, soft stools, breathing rattles, inactivity, red matter in the
region of nose, mouth, forelimbs, or dorsal head, and deaths at 3,500
mg/kg/day HDT.
7. A developmental toxicity study in rabbits given doses of 0, 75,
175, and 350 mg/kg/day with a developmental NOEL of 175 mg/kg/day
(insufficient litters were available at 350 mg/kg/day to assess
developmental toxicity); a maternal NOEL of 175 mg/kg/day based on
increased incidence of soft stool, diarrhea, nasal discharge, and
deaths at 350 mg/kg/day HDT.
8. A multigeneration reproduction study with rats fed dosage levels
of 0, 3, 10, and 30 mg/kg/day with the parental no-observed-effect
level/lowest observed effect level (NOEL/LOEL) 30 mg/kg/day HDT. The
only effect observed was an increased incidence of focal tubular
dilation of the kidney (both unilateral and bilateral combined) in the
high-dose male F3b pups. Since the focal tubular dilation of the
kidneys was not observed at the 1,500 mg/kg/day level HDT in the rat
reproduction study discussed below, but was observed at the 30 mg/kg/
day level HDT in the three-generation rat reproduction study the latter
was a spurious rather than glyphosate-related effect. Therefore, the
parental and reproductive (pup) NOELs are 30 mg/kg/day.
9. A two generation reproduction study with rats fed dosage levels
of 0, 100, 500, and 1,500 mg/kg/day with a systemic NOEL of 500 mg/kg/
day based on soft stools in F0 and F1 males and females at 1,500 mg/kg/
day HDT and a reproductive NOEL 1,500 mg/kg/day HDT.
10. Mutagenicity data included chromosomal aberration in vitro (no
aberrations in Chinese hamster ovary cells were caused with and without
S9 activation); DNA repair in rat hepatocyte; in vivo bone marrow
cytogenic test in rats; rec-assay with B. subtilis; reverse mutation
test with S. typhimurium; Ames test with S. typhimurium; and dominant-
lethal mutagenicity test in mice (all negative).
II. Dose Assessment Response
1. Reference Dose (RfD). The RfD represents the level at or below
which daily aggregate dietary exposure over a lifetime will not pose
appreciable risks to human health. The RfD is determined by using the
toxicological end point or the NOEL for the most sensitive mammalian
toxicological study. To assure the adequacy of the RfD, the Agency uses
an uncertainly factor in deriving it. The factor is usually 100, based
on the assumption that certain segments of the human population could
be as much as 100 times more sensitive than the species represented by
the toxicology. The Agency has determined a RfD of 2.0 mg/kg/day based
on the maternal toxicity NOEL of 175 mg/kg/day from the developmental
study with rabbits. The LOEL of 350 mg/kg/day HDT was based on
treatment related findings of diarrhea, nasal, discharge, and death
(62.5% of the does died by gestation day 21). Developmental toxicity
was not observed at any dose tested.
2. Carcinogenicity classification. The carcinogenic potential of
glyphosate was first considered by a panel, then called the Toxicology
Branch AD Hoc Committee, in 1985. The Committee, in a consensus review
dated March 4, 1985, classified glyphosate as a Group C carcinogen
based on an increased incidence of renal tumors in male mice. The
Committee also concluded that dose levels tested in the 26-month rat
study were not adequate for assessment of glyphosate's carcinogenic
potential in this species. These findings, along with additional
information, including a reexamination of the kidney slides from the
long-term mouse study, were referred to the FIFRA Scientific Advisory
Panel (SAP). In its report dated February 24, 1986, SAP classified
glyphosate as a Group D Carcinogen (inadequate animal evidence of
carcinogenic potential). SAP concluded that, after adjusting for the
greater survival in the high-dose mice compared to concurrent controls,
that no statistically significant pairwise differences existed,
although the trend was significant.
The SAP determined that the carcinogenic potential of glyphosate
could not be determined from existing data and proposed that the rat
and/or mouse studies be repeated in order to classify these equivocal
findings. On reexamination of all information, the Agency classified
glyphosate as a Group D Carcinogen and requested that the rat study be
repeated and that a decision on the need for a repeat mouse study would
be made upon completion of review of the rat study.
Upon receipt and review of the second rat chronic feeding/
carcinogenicity study, all toxicological findings for glyphosate were
referred to the Health Effects Division Carcinogenicity Peer Review
Committee on June 26, 1991, for discussion and evaluation of the weight
of evidence on glyphosate with particular emphasis on its carcinogenic
potential. The Peer Review Committee classified glyphosate as a Group E
(evidence of noncarcinogenicity for humans), based upon lack of
convincing carcinogenicity evidence in adequate studies in two animal
species. This classification is based on the following findings: (1)
None of the types of tumors observed in the studies (pancreatic islet
cell adenomas in male rat, thyroid c-cell adenomas and/or carcinomas in
male and female rats, hepatocellular adenomas and carcinomas in male
rats, and renal tubular neoplasms in male mice) were determined to be
compound related; (2) glyphosate was tested up to the limit dose on the
rat and up to levels higher than the limit dose in mice; and (3) there
is no evidence of genotoxicity for glyphosate.
III. Non-Dietary (Residential and Other Non-Occupational) Exposure
Assessment
Glyphosate is registered for use on non-food sites such as around
ornamental, shade trees, shrubs, walks, driveways, flowerbeds, home
lawns, farmsteads including building foundations, along and in fences,
in dry ditches and canals, along ditchbanks, farm roads, shelterbelts,
forestry, Christmas trees, and industrial sites and other noncrop or
industrial areas such as airports, lumber yards, manufacturing sites,
utility substations, parking areas, petroleum tank farms, and pumping
station.
Margins of Exposure (MOE's) are determined for non-dietary exposure
based on toxicological endpoints and measured or estimated exposures.
Since glyphosate is a group E chemical (evidence of non-carcinogenicity
for humans), the 21 day dermal study lacked any observable effects at
the limit dose, and no adverse effects were observed in developmental
toxicity studies in rats up to 1,000 mg/kg/day and rabbits up to 175
mg/kg/day, no toxicological endpoints are applicable. Because available
data indicated no evidence of significant toxicity via the dermal or
inhalations routes, MOE`s were not calculated and risk assessments are
not required for non-occupational (residential uses).
[[Page 17725]]
Some glyphosate end-use products (non ``homeowner'' uses only) are
in Toxicity Categories I and II for dermal and eye irritation and have
been associated with illness or injuries related to skin or eye
irritation. Under the protective clothing requirements of the Worker
Protection Standards (WPS), handlers of these products are expected to
be adequately protected.
IV. Dietary Exposure Assessment
The use of a pesticide may result directly or indirectly, in
residues in food. Primary residues or indirect/ inadvertent residues in
the agricultural commodities harvested from the crop cultured with the
aid of pesticide are determined by chemical analysis. To account for
the diversity of growing conditions, culture practices, soil types,
climatic conditions, crop varieties and method of use of the pesticide,
data from studies that represent the resulting commodities are
collected and evaluated to determine an appropriate level of the
residue that would not be exceeded if the pesticide is used as
represented in the studies. Available field trial data for glyphosate
support these tolerances. However, because of the recent imposition of
additional field trial data for specific geographical representation,
additional field trial data are required for corn and grain sorghum.
Because insufficient time has elapsed since imposition of these
requirements the petitioner is being granted conditional registrations
while obtaining the data. The conduct of the field trial and guidelines
for determining the residues are given in EPA ``OPPTS Test Guidelines,
Series 860, Residue Chemistry, August 28, 1996. See Federal Register,
61 FR 44308-44311 for availability of document.
The nature of the residue in plants and animals is adequately
understood and consists of the parent, glyphosate. The Agency has
decided that only glyphosate parent is to be regulated in plant and
animal commodities and that the major metabolite, AMPA
(aminomethylphosphonic acid) is not of toxicological concern regardless
of its levels in food.
Secondary residues in animal commodities are expected from these
uses. However, the established livestock tolerances are adequate to
cover secondary residues which may result from feeding field corn (both
conventional and genetically modified), and sorghum commodities with
residues of glyphosate to animals. Since no U.S. registration has been
proposed for oats, it has been concluded that oat feed items are not
likely to enter channels of trades in the United States.
V. International Harmonization
Codex MRL`s for the residues of glyphosate exist in maize and the
straw and fodder, dry cereal grains at 0.1 and 100 ppm respectively.
Mexican limits on maize exist at 0.1 ppm. Canadian limits on all other
food crops exist at 0.1 ppm. MRL`s of 20 ppm, 10 ppm, and 0.1 ppm on
oats are established/pending for CODEX, Canada, and Mexico,
respectively. Codex MRLS were established based on preplant/preemergent
use of glyphosate and are identical to the existing tolerances for
these crops under the same us conditions in the United States. The
increased tolerances now being proposed on corn and sorghum are based
on new preharvest uses of glyphosate in the United States. The import
tolerance being proposed for oats is being proposed to harmonize with
other international MRL's. The Agency suggests the petitioner consider
providing all relevant studies to Codex once the U.S. tolerances are
established in order that the Codex MRLs may be amended to accommodate
the use needs of the United States.
Adequate enforcement methods are available for analysis of residues
of glyphosate in or on plant commodities. These methods include GLC
(Method I in Pesticides Analytical Manual (PAM) II; the limit of
detection is 0.05 ppm). and HPLC with fluormetric detection. Use of the
GLC method is being discouraged due to lengthiness of the procedure.
The HPLC method has undergone successful Agency validation and has been
published in PAM II. A GC/MS method for glyphosate in crops has also
been validated by the Agency. This method has not yet been submitted
for publication in PAM II.
VI. Aggregate Exposure Assessment
1. Acute dietary. There is no concern for acute effects due to
dietary exposure to glyphosate.
2. Chronic dietary. Using the Dietary Risk Evaluation System
(DRES), a routine chronic exposure analysis was performed for
glyphosate. The chronic analysis for glyphosate is a worst case
estimate of dietary exposure with all residues at tolerance levels and
100% of the commodities assumed to be treated with glyphosate.
3. Drinking water. In examining aggregate exposure, FQPA directs
EPA to consider available information concerning exposures from the
pesticide residue in food and all other non-occupational exposures. The
primary non-food sources of exposure the Agency looks at include
drinking water (whether from groundwater or surface water), and
exposure through pesticide use in gardens. lawns, or buildings
(residential and other indoor uses).
The lifetime health advisory and maximum contaminant level (MCL),
for glyphosate are the same and given as 700 parts per billion in the
U.S. EPA Office of Drinking Water`s ``Drinking Water Health Advisory;
Pesticides.'' Environmental Fate data for glyphosate indicate little
potential for the7 chemical to migrate to ground water, but some
potential for residues to migrate to surface waters. Glyphosate is not
highly mobile and not persistent in a soil or water environment.
Because the Agency lacks sufficient water-related exposure data to
complete a comprehensive drinking water risk assessment for many
pesticides, EPA has commenced and nearly completed a process to
identify a reasonable yet conservative bounding figure for the
potential contribution of water related exposures to the aggregate risk
posed by a pesticide. In developing the bounding figure, EPA estimated
residue levels in water for a number of specific pesticides using
various data sources. The Agency then applied the estimated residue
levels, in conjunction with appropriate toxicological endpoints (RfD`s
or acute dietary NOEL`s) and assumptions about body weight and
consumption, to calculate, for each pesticide, the increment of
aggregate risk contributed by consumption of contaminated water. 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 glyphosate to
exceed the RfD if the tolerances being considered in this document were
granted. The Agency has therefore concluded that the potential
exposures associated with glyphosate in water, even 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.
4. Non occupational (residential) and non-dietary. Glyphosate is
registered for residential uses. As part of the hazard assessment
process, the Agency reviews the available toxicological database to
determine the endpoints of concern. For glyphosate, the Agency does not
have a concern for acute, short-term, or intermediate occupational or
residential risk since the available data do not indicate any evidence
of significant toxicity by the dermal or inhalation routes, or from a 1
day or single event exposure by the oral route. Therefore, an
[[Page 17726]]
acute, a short-term, or intermediate-term occupational or residential
risk assessment was not required.
As part of the hazard assessment process it was determined that a
chronic residential assessment was not necessary. The exposures which
would result from the use of glyphosate were determined to be of an
intermittent nature. The frequency and duration of these exposures do
not exhibit a chronic exposure pattern. The exposures do not occur
often enough to be considered a chronic exposure i.e., a continuous
exposure that occurs for at least several months. Therefore,
residential exposures were not aggregated with dietary exposures in
estimating chronic risk.
6. Cumulative exposure to substances with common mechanism of
toxicity. Section 408 (b)(2)(D)(v) requires that, when considering
whether to establish, modify, or revoke a tolerance, the Agency
consider ``available information'' concerning the cumulative effects of
a particular pesticide`s residues and ``other substances that have a
common mechanism of toxicity.'' The Agency believes that ``available
information'' in this context might include not only toxicity,
chemistry, and exposure data, but also scientific policies and
methodologies for understanding common mechanisms of toxicity and
conducting cumulative risk assessments. For most pesticides, although
the Agency has some information in its files that may turn out to be
helpful in eventually determining whether a pesticide shares a common
mechanism of toxicity with any other substances, EPA does not at this
time have the methodologies to resolve the complex scientific issues
concerning common mechanism of toxicity in a meaningful way. EPA has
begun a pilot process to study this issue further through examination
of particular classes of pesticides. The Agency hopes that the results
of this pilot process will increase the Agency`s scientific
understanding of this question such that EPA will be able to develop
and apply scientific principles for better determining which chemicals
have a common mechanism of toxicity and evaluating the cumulative
effects of such chemicals. The Agency anticipates, however, that even
as its understanding of the science of common mechanisms increases,
decisions on specific classes of chemicals will be heavily dependent on
chemical specific data, much of which may not be presently available.
Although at present the Agency does not know how to apply the
information in its files concerning common mechanism issues to most
risk assessments, there are pesticides as to which the common
mechanisms issues can be resolved. These pesticides include pesticides
that are toxicologically and structurally dissimilar to existing
chemical substances (in which the Agency can conclude that it is
unlikely that a pesticide shares a common mechanism of activity with
other substances) and pesticides that produce a common toxic metabolite
(in which case common mechanism of activity will be assumed).
EPA does not have, at this time, available data to determine
whether glyphosate 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 common mechanism of toxicity,
glyphosate 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 glyphosate has a common mechanism of toxicity
with other substances. A condition of the registrations associated with
these tolerances will be that the registrant will provide common
mechanism data in a timely manner when and if the Agency asks for it.
After EPA develops methodologies for more fully applying common
mechanism of toxicity issues to risk assessments, the Agency will
develop a process (either as a part of the periodic review of
pesticides or otherwise) to reexamine those tolerance decisions made
earlier.
VII. Determination of Safety for the U.S. Population and Nonnursing
Infants
Using the Dietary Risks Evaluation System (DRES) a chronic analysis
was based on 100% of the crop treated and all residues at tolerance
levels. Based on the dietary risk assessment the proposed uses utilize
0.115% of the RfD for U.S. population; 0.189% of the RfD for non-
nursing infants under 1 year old; 0.84 of the RfD for nursing infants
under 1 year old; 0.866% of the RfD for children 1 to 6 years old; and
0.443% of the RfD for children 7 to 12 years old. Total aggregate
exposure from glyphosate residues in food, taking into account existing
and proposed uses, uses 1% of the RfD for the overall U.S. population
and nursing infants: 3% of the RfD for nonnursing infants under 1 year
old and children 1 to 6 years old; 3%; and 2% of the RfD for children 7
to 12 years old. An additional risk assessment for residential uses was
not required because of no evidence of significant toxicology via
dermal or inhalation routes. Even though the Agency has not 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 glyphosate to exceed the RfD. EPA concluded that there
is reasonable certainty that no harm will occur from aggregate exposure
to glyphosate.
VIII. Determination of Safety for Infants and Children
FFCDA section 408 provides that EPA shall apply an additional
tenfold margin of exposure (safety) for infants and children in the
case of threshold effects to account for pre-and post-natal toxicity
and the completeness of the database unless EPA determines that a
different margin of exposure (safety) will be safe for infants and
children. Margins or exposure (safety) are often referred to as
uncertainty (safety) factors. EPA believes that reliable data support
using the standard margin of exposure (usually 100x for combined inter-
and intra-species variability) and not the additional tenfold margin of
exposure when EPA has a complete data base under existing guidelines
and when the severity of the effect in infants and children or the
potency or unusual toxic properties of a compound do not raise concerns
regarding the adequacy of the standard margin of exposure.
Risk to infants and children was determined by the use of two
developmental toxicity studies in rats and rabbits and the two-
generation reproduction study in rats discussed below. The
developmental toxicity studies evaluates the potential for adverse
effects on the developing organism resulting from exposure during
prenatal development. The reproduction study provides information
relating to effects from exposure to the chemical on the reproductive
capability of both (mating) parents and on systemic toxicity.
The toxicological database for evaluating pre- and post-natal
toxicity for glyphosate is considered to be complete at this time. In
the rabbits, no developmental toxicity was observed at doses where
significant maternal toxicity was noted (death and clinical signs at
350 mg/kg/day, highest dose tested HDT. In the rat developmental
toxicity study, maternal (systemic) toxicity was noted at 3,500 mg/kg/
day, HDT as diarrhea, decreased mean body weight gain, breathing
rattles, inactivity, red matter around the nose and mouth, and on
forelimbs and dorsal head, decreases in total implantations/dam and
inviable fetuses/dam and death (24% of the group). The developmental
(pup) NOEL is 1,000 mg/kg/day. The
[[Page 17727]]
developmental (pup) toxicity was exhibited only in the high dose as
increased numbers of litters and fetuses with unossified sternebrae,
and decreased mean fetal body weights. However, these developmental
effects were assumed to be due to the extreme maternal toxicity. No
effects on reproductive parameters were observed.
In the rat two-generation reproduction study, parental toxicity was
observed at 1,500 mg/kg/day as soft stools, decreased food consumptions
and body weight gain. The developmental (pup) toxicity was also only
exhibited at 1,500 mg/kg/day as decreased body weight gain of the F1a,
F2a, and F2b male and female pups during the second and third weeks of
lactation.
The RfD is based on the NOEL for maternal toxicity in the rabbit
developmental study. No developmental effects were noted in the study.
In the rat developmental study effects were noted only at 20x higher
than the NOEL used for the RfD. No pre- or post-natal effects were seen
in any study absent maternal toxicity. In the rat reproduction study
developmental effects were noted at 5x the NOEL used for the RfD. The
Agency does not believe the effects seen in these studies are of such
concern to require an additional safety factor. Accordingly, the Agency
believes the RfD has an adequate margin of protection for infants and
children. The percent RfD utilized by glyphosate is from 1% for nursing
infants (less than 1 year old) to 3% for non-nursing infants and
children 1 to 6 years old. EPA concluded that there is reasonable
certainty that no harm will occur to infants and children from
aggregate exposure to glyphosate.
IX. Other Considerations
Endocrine effects. No specific tests have been conducted with
glyphosate to determine whether the chemical may have an effect in
humans that is similar to an effect produced by a naturally occurring
estrogen or other endocrine effects. However, there are no significant
findings in other relative toxicity studies, i.e., teratology and
multi-generation reproductive studies which would suggest that
glyphosate produces these kinds of effects.
X. Data Gaps
Data desirable but lacking for these tolerances include specific
geographic representative grain sorghum and corn field residue trials.
Because of insufficient time since the imposition of additional data
requirements the Agency is requiring that this data be submitted as a
condition of registration.
Based on the information cited above, the Agency has determined
that the establishment of these tolerances by amending 40 CFR part 180
will be safe, therefore the tolerances are established as set forth
below.
In addition to the time-limited tolerances being amended, since for
purposes of establishing tolerances FQPA has eliminated all
distinctions between raw and processed food, EPA is combining the
tolerances that now appear in Secs. 185.3500 and 186.3500 with the
tolerances in Sec. 180.364 and is eliminating Secs. 185.3500 and
186.3500.
XI. Response to Comment
The one commenter raised several concerns regarding these
tolerances.
1. Increased exposure. The commenter was concerned that approval of
these tolerances would lead to increased exposure to glyphosate because
it would enhance Monsanto`s ability to market glyphosate-tolerant corn
and thus use glyphosate. The commentor argued that therefore approval
of the tolerances would not protect the public health rather it would
increase risk.
EPA response. Approval of these tolerances may lead to higher
exposure the glyphosate residues. That is the case when ever EPA
approves a new tolerance. The question before EPA in ruling on a
tolerance petition is whether the tolerance meets the FFDCA`s safety
standard. As detailed above, EPA has concluded that these tolerances do
meet the reasonable certainty of no harm standard. This standard
requires consideration of exposure to glyphosate from existing uses as
well as exposure from the uses covered by the tolerances in the
petition before EPA.
2. Glyphosate residues in foods derived from animals. The commenter
asked EPA to confirm that the major route of exposure resulting from
these tolerances would be from foods derived from animals. The
commenter also asked how the tolerances would effect the level of
glyphosate residues in animal feeds and what percentage of glyphosate
treated corn would be consumed by humans.
EPA response. The nature of glyphosate residue in plants and
animals has been explored by various studies that have been reviewed by
the Agency. A separate peer review committee ``Metabolism Committee''
evaluated glyphosate plant and animal commodities and decided that the
major metabolite is not of toxicological concern regardless of its
level in food. Due to the use pattern of glyphosate, secondary residues
in animal commodities are expected. Corn grain, forage, fodder, and
aspirated grain fractions are animal feed items. Based on the proposed
tolerances on aspirated grain fractions, corn stover, forage, and
grain, the dietary burden of at most 78 ppm glyphosate residue in/on
corn commodities, (if all corn commodities (including corn genetically
altered to be tolerant to glyphosate) are fed)) will be covered by the
tolerances currently established on meat, milk, eggs, and livestock
commodities including the recently (April 5, 1996, 61 FR 15192)(FRL-
5351-1), established tolerances on kidney of cattle, goats, hogs,
horses, poultry, and sheep at 4 ppm. A chronic (long-term) dietary
exposure analysis (DRES) was performed for the use of glyphosate in/on
corn. The Agency used the following conservative (worst-case)
assumptions: all corn (including genetically altered corn) would have
the same tolerance level residues, and that 100 percent of the crop is
treated. It is not believed that actual residues would reach tolerance
levels, or that 100 percent of the total corn crop would be treated
with glyphosate. The Agency feels that the risk to human health does
not exceed a level of concern (100%) due to the percent of the RfD
using the ``worst case'' assumptions. These dietary risk numbers
include corn consumed directly by humans, plus meat, milk and eggs from
which animals consumed corn raw agricultural commodities as feed.
Published and proposed glyphosate tolerances result in the following
percents of the RfD used: 1% for the overall U.S. population and
nursing infants, 2% for children (7 to 12 years old), and 3% non-
nursing infants less than 1 year old and children (1 to 6 years old).
3. Toxicology concerns. The commenter challenged Monsanto's
assertions that glyphosate was of low toxicity. The commenter cited the
fact that glyphosate ranked number 3 in California for acute illnesses
in agriculture from 1984-1990. The commenter claimed that glyphosate is
a skin and eye irritant, a possible carcinogen, a mutagen, and a
reproductive toxicant. In support of glyphosate`s carcinogenicity, the
commenter claimed that one of the metabolites or breakdown products of
glyphosate is formaldehyde and the commenter asserted that formaldehyde
is a carcinogen, mutagen, and reproductive toxicant.
Additionally, the commenter claimed that a study showed that
glyphosate decreased lung function and that studies showed that
glyphosate inhibits enzymes involved in the detoxification of
chemicals.
[[Page 17728]]
4. Acute illnesses and skin and eye irritation--EPA response. Data
indicate that technical-grade glyphosate is in Toxicity Category III
and Toxicity Category IV and that technical glyphosate is not a dermal
sensitizer. Some formulations of glyphosate are in Category I and II
where skin and eye irritation were associated with acute illnesses.
Some of these formulations are being phased out of the U.S. market.
Handlers and users of remaining formulations in Category I and II are
expected to be adequately protected by the protective clothing
requirements of the Worker Protection Standards (WPS). Data reviewed by
the Agency on current formulations place these formulations in Toxicity
Category III and IV.
5. Carcinogen, mutagen and reproductive toxicity--EPA response.
Data indicate that glyphosate is a group E carcinogen (evidence of
noncarcinogenicity for studies in humans, causes no pre- or post-natal
effects in any study absent maternal toxicity, and is not a mutagen
(refer to toxicology discussion above for a detailed discussion of
carcinogenicity, reproductive, developmental and mutagenicity testing).
6. Formaldehyde--EPA response. Available rat metabolism data,
residue data, and environmental data indicate that the major metabolite
of glyphosate is AMPA which is further degraded by soil microbes to
CO2. The Agency has determined that AMPA is not of
toxicological concern. (Glyphosate Reregistration Eligibility Decision
(RED) issued by EPA September 1993). Available data do not indicate
that formaldehyde is a metabolite or a degradate of glyphosate.
7. Decreased lung function--EPA response. Data reviewed by the
Agency for glyphosate formulations for acute inhalation place most
glyphosate formulations in Toxicity Category III and IV for acute
inhalation. The Agency believes that handlers of these formulations and
any formulations that may be Toxicity Category I or II are expected to
be adequately protected by the protective clothing required by WPS.
8. Interference with enzymes--EPA response. The mode of action for
glyphosate does involve interference with enzymes that result in the
death of plants by inhibiting the biosynthesis of aromatic amino acids
which along with other biochemical changes results in the death of
plants. This is a common mode of action for various pesticides, but the
Agency has no information that indicates that the handling or ingestion
of glyphosate in small amounts result in interference with enzymes in
the human body.
9. Inert Ingredients. The commentor also contended that EPA must
examine the toxicity of the inert ingredients in glyphosate products in
setting these tolerances.
EPA response. These tolerances establish maximum legal levels of
residues of the active ingredient glyphosate that can be present in
certain foods. These tolerances do not legalize any inert ingredients
in glyphosate products. If a pesticide product also contains inert
ingredients, those inert ingredients must have tolerances or exemptions
from the requirement or their presence in food will render the food
adulterated. Before approving a pesticide registration under the
Federal Insecticide, Fungicide, and Rodenticide Act, 7 U.S.C. 136 et
seq., EPA checks to make sure that all needed tolerances or exemptions
are in place. All inerts present in current glyphosate formulations for
use on food crops either have tolerances or exemptions from tolerances.
Additionally, under the FIFRA registration process, EPA evaluates the
potential risks posed by inert ingredients. The Agency requires a full
disclosure of inert ingredients for each Roundup formulation to
determine acute toxicity such as acute eye, skin, inhalation, and
dermal sensitization. Refer to previous discussions on skin, eye, and
acute inhalation for discussion of formulations.
10. Persistence in soil. The commenter claimed that glyphosate
persists in soils from 3 to 141 days.
EPA response. Data from background field dissipation trials from
eight sites show that the median half-life (DT50) for glyphosate
applied at maximum use rates was 13.9 days with a range of 2.6 (Texas)
to 140.6 (Iowa) days. Acceptable aerobic soil, aerobic aquatic, and
anaerobic aquatic metabolism studies demonstrate that under those
conditions at 25 deg.C in the laboratory, glyphosate degrades rapidly
with half-lives of approximately 2,7, and 8 days respectively. The
reported half-lives from the field studies conducted in the coldest
climates, i.e. Minnesota, New York, and Iowa, were the longest at 28.7
days, 127.8 days, and 140.6 days respectively indicating that
glyphosate residues in the field are somewhat more persistant in cooler
climates as opposed to milder ones (Georgia, California, Arizona, Ohio,
and Texas. AMPA was the major degradate in all studies. AMPA has been
determined to not be of toxicological concern. (Glyphosate
Reregistration Eligibility Decision (RED) issued by EPA September,
1993).
11. Environmental effects. The commenter also claimed that data was
lacking regarding glyphosate`s toxicity to soil invertebrates,
reptiles, and amphibians.
EPA response. Environmental Effects are considered under FIFRA. In
examining glyphosate under FIFRA the Agency required several tests with
mammals; acute tests to birds, fish, aquatic invertebrates, and bees;
subacute dietary testing on birds; avian reproduction; and chronic
testing on freshwater fish and freshwater invertebrates. Data submitted
to and reviewed by the Agency indicate that effects to birds, mammals,
fish, and invertebrates are minimal. (Glyphosate Registration
Eligibility Decision (RED) issued by EPA September, 1993).
XII. Objections and Hearing Requests
The new FFDCA section 408 (g) provides essentially the same process
for persons to ``object'' to a tolerance regulation issued by EPA under
the new section 408 (e) and (1)(6) as was provided in the old section
408 and section 409. However, the period for filing objections is 60
days rather than 30 days. EPA currently has procedural regulations
which governs the submission of objections and hearing requests. These
regulations will require some modification to reflect the new law.
However, until those modifications can be made, EPA will continue to
use those procedural regulations with appropriate adjustments to
reflect the new law.
Any person adversely affected by this regulation may, by June 10,
1997, file written objections to any aspect of this regulation
(including the automatic revocation provision) and may also request a
hearing on those objections. Objections and hearing requests must be
filed with the Hearing Clerk, at the address given below (40 CFR
178.20). A copy of the objections and/or hearing requests filed with
the Hearing Clerk should be submitted to the OPP docket for this
rulemaking. The objections submitted must specify the provisions of the
regulation deemed objectionable and the grounds for the objections (40
CFR 178.25). Each objection must be accompanied by the fee prescribed
by 40 CFR 180.33(i). If a hearing is requested, the objections must
include a statement of the factual issue(s) on which the hearing is
requested, the requestor`s contentions on each such issue, and a
summary of any evidence relied upon by the objector (40 CFR 178.27). A
request for a hearing will be granted if the Administrator determines
that the material submitted shows the following: There is a genuine and
[[Page 17729]]
substantial issue of fact; there is a reasonable possibility that
available evidence identified by the requestor would, if established,
resolve one or more issues in favor of the requestor, taking into
account uncontested claims or facts to the contrary; and resolution of
the factual issue(s) in the manner sought by the requestor would be
adequate to justify the action requested. (40 CFR 178.32). Information
submitted in connection with an objection or hearing request may be
claimed confidential by marking any or all of that information as
``Confidential Business Information'' (CBI). Information marked as CBI
will not be disclosed except in accordance with procedures set forth in
40 CFR part 2, A copy of the information 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.
XIII. Public Docket
EPA has established a record for this rulemaking under docket
number [OPP-300469; PP 8F3672, 8F3673, 5F4555, 6E4645] (including any
comments and data submitted electronically). 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 public record is located in Room 1132 of the Public
Response and Program Resources Branch, Field Operations Division
(7506C), Office of Pesticide Programs, Environmental Protection Agency,
Crystal Mall #2, 1921 Jefferson Davis Highway, Arlington, VA.
Electronic comments may be sent directly to EPA at:
opp-docket@epamail.epa.gov.
Electronic comments must be submitted as an ASCII file avoiding the
use of special characters and any form of encryption.
The official record for this rulemaking, as well as the public
version, as described above will be kept in paper form. Accordingly,
EPA will transfer any copies of objections and hearing requests
received electronically into printed, paper form as they are received
and will place the paper copies in the official rulemaking record which
will also include all comments submitted directly in writing. The
official rulemaking record is the paper record maintained at the
address in ADDRESSES at the beginning of this document.
XIV. Regulatory Assessments Requirements
Under Executive Order 12866 (58 FR 51735, October 4, 1993), this
action is not a ``significant regulatory action'' and, since this
action does not impose any information collection requirements subject
to approval under the Paperwork Reduction Act, 44 U.S.C. 3501 et seq.,
it is not subject to review by the Office of Management and Budget. In
addition, this action does not impose any enforceable duty, or contain
any ``unfunded mandates'' as described in Title II of the Unfunded
Mandates Reform Act of 1995 (Pub. L. 104-4), or require prior
consultation as specified by Executive Order 12875 (58 FR 58093,
October 28, 1993), or special consideration as required by Executive
Order 12898 (59 FR 7629, February 16, 1994).
Because tolerances established on the basis of a petition under
section 408(d) of FFDCA do not require issuance of a proposed rule, the
regulatory flexibility analysis requirements of the Regulatory
Flexibility Act (RFA), 5 U.S.C. 604(a), do not apply. Prior to the
recent amendment of the FFDCA, EPA had treated such rulemakings as
subject to the RFA; however, the amendments to the FFDCA clarify that
no proposal is required for such rulemakings and hence that RFA is
inapplicable. Nonetheless, the Agency has previously assessed whether
establishing tolerances or exemptions from tolerance, raising tolerance
levels, or expanding exemptions adversely impact small entities and
concluded, as a generic matter, that there is no adverse impact. (46 FR
24950, May 4, 1981).
Pursuant to 5 U.S.C. 801 (a)(1)(A), EPA submitted a report
containing this rule and other required information to the U.S. Senate,
the U.S. House of Representatives and the Comptroller General of the
General Accounting Office prior to publication of this rule in today`s
Federal Register. This rule is not a major rule as defined by 5 U.S.C.
804(2).
List of Subjects
40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agriculatural commodities, Pesticides and pest, Reporting and
recordkeeping requirements.
40 CFR Part 185
Environmental protection, Food additives, Pesticides and pests.
40 CFR Part 186
Environmental protection, Animal feeds, Pesticides and pests.
Dated: March 28, 1997.
Peter Caulkins,
Acting Director, Registration Division, Office of Pesticide Programs.
Therefore, chapter I of title 40 of the Code of Federal Regulations
is amended as follows:
PART 180--#[AMENDED]
1. In part 180:
a. The authority citation for part 180 continues to read as
follows:
Authority: 21 U.S.C. 346a and 371.
b. Section 180.364 is amended as follows:
i. By adding a paragraph heading to paragraph (a), and in the table
by revising the entry ``Grain crops (except wheat)'' and alphabetically
adding the commodities: aspirated grain fractions; corn, field, forage;
corn, field, grain; corn, field, stover; oats; sorghum, grain; and
sorghum, grain, stover.
ii. In paragraph (b) by transferring the entries in the table and
alphabetically adding them to the table in paragraph (a), by removing
the remaining text of paragraph (b), by adding a paragraph heading and
reserving paragraph (b).
iii. In paragraph (d) by transferring the entries in the table and
alphabetically adding them to the table in paragraph (a), by removing
the remaining text of paragraph (d).
iv. In paragraph (c) is amended by adding a paragraph heading,
``Indirect and inadvertent residues'', and redesignating the amended
paragraph (c) as new paragraph (d), and by adding a heading and
reserving new paragraph (c).
Sec. 180.364 Glyphosate, tolerances for residues.
(a) General. * * *
------------------------------------------------------------------------
Parts Per
Commodity Million
(ppm)
------------------------------------------------------------------------
* * * * *
Aspirated grain fractions.................................. 200.0
* * * * *
Corn, field, forage........................................ 1.0
Corn, field, grain......................................... 1.0
Corn, field, stover........................................ 100.0
* * * * *
Grain crops (except wheat, corn, oats, and grain sorghum).. 0.010
* * * * *
Oats, grain................................................ 20.0
* * * * *
Sorghum, grain............................................. 15.0
Sorghum, grain, stover..................................... 40.0
[[Page 17730]]
* * * * *
------------------------------------------------------------------------
(b) Section 18 emergency exemptions. [Reserved]
(c) Tolerances with regional registrations. [Reserved]
(d) Indirect or inadvertent residues. * * *
PART 185--[AMENDED]
2. In part 185:
a. The authority citation for part 185 continues to read.
Authority: 21 U.S.C. 346a and 348.
Sec. 185.3500 [Removed]
b. In Sec. 185.3500 by transferring the entries in the tables to
paragraphs (a)(1), (2), and (3), and alphabetically adding them to the
table in paragraph (a) of Sec. 180.364, and by removing the remainder
of Sec. 185.3500.
PART 186--[AMENDED]
3. In part 186:
a. The authority citation for part 185 continues to read.
Authority: 21 U.S.C. 342, 348 and 701.
Sec. 186.3500 [Removed]
b. In Sec. 186.3500 by transferring the entries in the tables to
paragraphs (a) and (b) and alphabetically adding them to the table in
paragraph (a) of Sec. 180.364, and by removing the remainder of
Sec. 186.3500.
[FR Doc. 97-9231 Filed 4-10-97; 8:45 am]
BILLING CODE 6560-50-F
