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Glyphosate - Pesticide Tolerance 10/98

[Federal Register: October 8, 1998 (Volume 63, Number 195)]
[Rules and Regulations]
[Page 54058-54066]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr08oc98-10]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-300736; FRL 6036-1]
RIN 2070-AB78
Glyphosate; Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This regulation establishes tolerances for residues of
glyphosate N-(phosphonomethyl) glycine in or on durian, mangosteen, and
rambutan. The Interregional Research Project 4 (IR-4) requested these
tolerances under the Federal Food, Drug, and Cosmetic Act (FFDCA), as
amended by the Food Quality Protection Act of 1996.

DATES: This regulation is effective October 8, 1998. Objections and
requests for hearings must be received by EPA on or before December 7,
1998.

ADDRESSES: Written objections and hearing requests, identified by the
docket control number, OPP-300736, must be submitted to: Hearing Clerk
(1900), Environmental Protection Agency, Rm. M3708, 401 M St., SW.,
Washington, DC 20460. Fees accompanying objections and hearing requests
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
requests filed with the Hearing Clerk identified by the docket control number,
OPP-300736, must also be submitted to: Public Information and Records
Integrity Branch, Information Resources and Services Division (7502C), 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. 119, Crystal Mall #2, 1921 Jefferson Davis Hwy.,
Arlington, VA.

    A copy of objections and hearing requests filed with the Hearing
Clerk may also be submitted electronically by sending electronic mail
(e-mail) to: opp-docket@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 5.1/6.1
or ASCII file format. All copies of objections and hearing requests in
electronic form must be identified by the docket control number OPP-
300736. 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.

FOR FURTHER INFORMATION CONTACT: By mail: Sidney Jackson, Registration
Division (7505C), Office of Pesticide Programs, Environmental
Protection Agency, 401 M St., SW., Washington, DC 20460. Office
location, telephone number, and e-mail address: Crystal Mall #2, 1921
Jefferson Davis Hwy., Arlington, VA, (703) 305-7610; e-mail:
jackson.sidney@epamail.epa.gov.

SUPPLEMENTARY INFORMATION: In the Federal Register of August 26, 1998
(63 FR 45487) (6023-5) EPA, issued a notice pursuant to section 408 of
the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(e)
announcing the filing of a pesticide petition (PP) for tolerance by the
Interregional Research Project 4. This notice included a summary of the
petition prepared by Monsanto Agricultural Group (MAG), the registrant.
There were no comments received in response to the notice of filing.

    The petition requested that 40 CFR 180.364 be amended by
establishing tolerances for residues of the herbicide glyphosate N-
(phosphonomethyl) glycine, in or on durian at 0.2 part per million
(ppm), mangosteen at 0.2 ppm, and rambutan at 0.2 ppm.

I. Risk Assessment and Statutory Findings

    Section 408(b)(2)(A)(i) of the FFDCA allows EPA to establish a
tolerance (the legal limit for a pesticide chemical residue in or on a
food) only if EPA determines that the tolerance is "safe." Section
408(b)(2)(A)(ii) defines "safe" to mean that "there is a reasonable
certainty that no harm will result from aggregate exposure to the
pesticide chemical residue, including all anticipated dietary exposures
and all other exposures for which there is reliable information." This
includes exposure through drinking water and in residential settings,
but does not include occupational exposure. Section 408(b)(2)(C)
requires EPA to give special consideration to exposure of infants and
children to the pesticide chemical residue in establishing a tolerance
and to "ensure that there is a reasonable certainty that no harm will
result to infants and children from aggregate exposure to the pesticide
chemical residue."

    EPA performs a number of analyses to determine the risks from
aggregate exposure to pesticide residues. For further discussion of the
regulatory requirements of section 408 and a complete description of
the risk assessment process, see the Final Rule on Bifenthrin Pesticide
Tolerances November 26, 1997 (62 FR 62961) (FRL 5754-7).

II. Aggregate Risk Assessment and Determination of Safety

    Consistent with section 408(b)(2)(D), EPA has reviewed the
available scientific data and other relevant information in support of
this action. EPA has sufficient data to assess the hazards of
glyphosate and to make a determination on aggregate exposure,
consistent with section 408(b)(2), for tolerances for residues of
glyphosate on durian at 0.2 ppm, mangosteen at 0.2 ppm, and rambutan at
0.2 ppm. EPA's assessment of the dietary exposures and risks associated
with establishing the tolerances follows.

A. Toxicological Profile

    EPA has evaluated the available toxicity data and considered its
validity, completeness, and reliability as well as the relationship of
the results of the studies to human risk. EPA has also considered
available information concerning the variability of the sensitivities
of major identifiable subgroups of consumers, including infants and
children. The nature of the toxic effects caused by glyphosate are
discussed below.

    1. Acute toxicity. The required battery of acute toxicity studies
was submitted and found adequate. The findings were as follows: an
acute oral study in rats shows a combined lethal dose
(LD)50 of > 5,000 milligram (mg)/kilogram (kg); an
acute dermal study in rabbit resulted in a LD50 of >
5,000 mg/kg; a primary dermal irritation and a primary dermal sensitization
study essentially showed no irritation and no sensitization, respectively. A
primary eye irritation study in the rabbit showed severe irritation for
glyphosate acid. However, glyphosate is normally formulated as one of several
salts, and eye irritation studies on the salts showed essentially no
irritation; a primary dermal irritation study showed essentially no
irritation; and a primary dermal sensitization study showed no
sensitization.
    Based on these results, the Agency concludes that the acute
toxicity and irritation potential of glyphosate is low.

    2. Genotoxicity. A number of mutagenicity studies were conducted
and were all negative. These studies included: chromosomal aberration
in vitro (no aberrations in Chinese hamster ovary cells were caused
with or without S9 activation); deoxyribonucleic acid (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.
Negative results were obtained when glyphosate was tested in a
dominant-lethal mutation assay.

    3. Reproductive and developmental toxicity. The oral rat and rabbit
developmental studies and the oral rat reproduction study demonstrated
no indication of increased sensitivity of rats or rabbits to in utero
and postnatal exposure to glyphosate.

     4. Developmental toxicity study in rats. Sprague-Dawley rats were
dosed by gavage at doses of 0, 300, 1,000, or 3,500 mg/kg/day during
days 6-15 of gestation. The maternal (systemic) no-observed adverse
effect level (NOAEL) is 1,000 mg/kg/day. The maternal (systemic)
lowest-observed effect level (LOAEL) of 3,500 mg/kg/day was based on
the following treatment-related effects: diarrhea, decreased mean body
weight gain, breathing rattles, inactivity, red matter around the nose
and mouth, and on forelimbs and dorsal head, and death (24% of the
group). The developmental (fetal) NOAEL is 1,000 mg/kg/day. The
developmental (fetal) LOAEL of 3,500 mg/kg/day was based on treatment-
related developmental effects observed only in the high-dose group of:
decreases in total implantations/dam and inviable fetuses/dam, increased
number of litters and fetuses with unossified sternebrae, and decreased mean
fetal body weights.

    5. Developmental toxicity study in rabbit. Dutch Belted rabbits
were gavaged during gestation days 6-27 at doses of 0, 75, 175, or 350
mg/kg/day. The maternal (systemic) NOAEL is 175 mg/kg/day. The maternal
(systemic) LOAEL of 350 mg/kg/day was based on treatment-related
effects that included: diarrhea, nasal discharge, and death (62.5% of
doses died by gestation day 21). The developmental (pup) NOAEL is
≥ 175 mg/kg/day (insufficient litters were available at 350
mg/kg/day to assess developmental toxicity). Developmental toxicity was
not observed at any dose.

    6. Three-generation reproduction study in rat. Sprague-Dawley rats
were dosed at 0, 3, 10, or 30 mg/kg/day (equivalent to 0, 30, 100 or
300 ppm). The parental NOAEL is ≥ 30 mg/kg/day highest dose
tested (HDT). The reproductive NOAEL was 10 mg/kg/day based on an
increased incidence of focal tubular dilation of the kidney (both
unilateral and bilateral combined) in the 30 mg/kg/day group 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 2-generation rat reproduction
(see below), but was observed at the 30 mg/kg/day level HDT in the 3-
generation rat reproduction study, the Agency's Reference Dose (RfD)
Committee concluded that the latter was a spurious rather than
glyphosate-related effect. Therefore, the parental and reproductive
(pup) NOAELs are ≥ 30 mg/kg/day.

     7. Two-generation reproduction study in rats. Sprague-Dawley rats
were tested at doses of 0, 2,000, 10,000, or 30,000 ppm (100, 500, or
1,500 mg/kg/day). Treatment-related effects observed in the high dose
group included: soft stools, very frequent, in the Fo
and F1 males and females, decreased food consumption
and body weight gain of the Fo and
F1 males and females during the growth premating
period, and decreased body weight gain of the F1a,
F2a and F2b male and female
pups during the second and third weeks of lactation. Focal tubular
dilation of the kidneys, observed in the 3-generation study, was not
observed at any dose level in this study.
    Based on the above findings, the parental and developmental (pup)
NOAEL's are 500 mg/kg/day and the parental and developmental (pup)
LOAEL's are 1,500 mg/kg/day. There were no adverse reproductive effects
at any dose level.

    8. Subchronic toxicity--

     i. In a 90-day feeding study in Sprague-Dawley rats at dietary levels of
0, 1,000, 5,000, or 20,000 ppm (50, 250, and 1,000 mg/kg/day) of glyphosate
technical, the NOAEL for systemic toxicity was considered less than 1,000 ppm
due to increased serum phosphorus and potassium at all treated doses in both
sexes and the occurrence of high dose pancreatic lesions in males (pancreas
not examined for low and mid-dose groups).
     ii. In a 90-day feeding study in CD-1 mice, dietary levels of 750,
1,500, or 7,500 mg/kg/day (8,000, 30,000, or 50,000 ppm) of technical
glyphosate resulted in a systemic NOAEL of 1,500 mg/kg/day with the
high dose LOAEL based on decreased weight gains of 24% and 18% in males
and females, respectively.
     iii. In a 21-day dermal toxicity study in New Zealand white
rabbits, glyphosate was applied to 10/sex/dose 5 with intact and 5 with
abraded skin at levels of 0, 10, 1,000, or 5,000 mg/kg/day. The rabbits
were exposed for 6 hours/day, 5 days/week, for 3 weeks. The systemic
NOAEL was 1,000 mg/kg/day and the LOAEL was 5,000 mg/kg/day, based on
decreased food consumption in males. Although serum lactate
dehydrogenase was decreased in both sexes at the high dose, this
finding was not considered to be toxicologically significant.
    The required 90-day feeding study in dogs is satisfied by the 1-
year dog feeding study.

    9. Chronic toxicity. A chronic feeding/carcinogenicity feeding

study in Sprague-Dawley rats was conducted for 26 months at dietary
levels of 0, 30, 100, or 300 ppm (3, 10, or 31 mg/kg/day). There were
no systemic effects in any of the parameters examined body weight, food
consumption, clinical signs, mortality, clinical pathology, organ
weights and histopathology. The systemic NOAEL was established at > 31
mg/kg/day.

    10. A second chronic toxicity/carcinogenicity study in Sprague-
Dawley rats was conducted at dietary levels of 0, 2,000, 8,000, or
20,000 ppm (89, 362, or 940 mg/kg/day) for males and 113, 457, or 1,183
mg/kg/day for females for 24 months. The systemic NOAEL was established
at 8,000 ppm and the LOAEL was identified at 20,000 ppm based on
decreased weight gains in the females and increased incidence of
cataracts and lens abnormalities, decreased urinary pH, increased
absolute liver weight and increased relative liver weight/brain weight
in males.

    11. In a 1-year chronic toxicity study in beagle dogs, glyphosate
technical was administered by gelatin capsule at levels of 0, 20, 100,
or 500 mg/kg/day. There were no systemic effects in all examined
parameters and the systemic NOAEL was established at > 500 mg/kg/day.

B. Toxicological Endpoints

    1. Acute toxicity. Acute dietary risk assessments are performed for
a food-use pesticide if a toxicological study has indicated the
possibility of an effect of concern occurring as a result of a one day
or single exposure. In glyphosate studies, an acute dietary endpoint
and dose was not identified in the toxicology data base. A review of
the rat and rabbit developmental studies did not provide a dose or
endpoint that could be used for acute dietary risk purposes.
Additionally, there were no data requirements for acute or subchronic
rat neurotoxicity studies since there was no evidence of neurotoxicity
in any of the toxicology studies at very high doses.
    The Agency concludes with reasonable certainty that glyphosate does
not elicit an acute toxicological response. An acute dietary risk
assessment is not required.

    2. Short - intermediate - and long- term toxicity dermal. In a 21-
day dermal toxicity study in rabbits with technical glyphosate, the
NOAEL was 1,000 mg/kg/day and the LOAEL was 5,000 mg/kg/day based on
decreased food consumption in females. Although the rabbit
developmental study had a maternal toxicity NOAEL of 175 mg/kg/day, use
of the 3% dermal absorption with this oral NOAEL of 175 mg/kg/day
yields a dermal NOAEL > 5,000 mg/kg/day. A LD50 >
2,000 and Toxicity Category III were determined in acute dermal toxicity
testing. Doses and endpoints were not identified for dermal and inhalation
route of exposure. This risk assessment is not required and a dermal
absorption factor is not applicable here in evaluating exposure/risk.

    3. Chronic toxicity. EPA has established the RfD for glyphosate at
2.0 mg/kg/day. The chronic RfD is based on a NOAEL = 175 mg/kg/day
based on death, diarrhea, and nasal discharge at 350 mg/kg/day LOAEL
with an uncertainty factor of 100. The data base for RfD determination
was developed from multiple species testing.
    Groups of 16/dose Dutch Belted rabbits were dosed with technical
glyphosate at doses of 0, 75, 175, or 350 mg/kg/day between gestation
days 6 to 27. Maternal effects were seen at only the high dose and
consisted of diarrhea, nasal discharge and death 10/16.
    Developmental effects were not seen at any dose tested. Therefore, the
NOAEL and LOAEL for maternal toxicity were 175 mg/kg/day and 350 mg/kg/
day, respectively. The NOAEL for maternal toxicity in the rabbit
developmental study was the lowest NOAEL of all the major studies which
include the 24-month mouse carcinogenicity study NOAEL = 750 mg/kg/day,
the 1-year dog study NOAEL = 500 mg/kg/day, 2-year chronic/onco rat
study NOAEL = 400 mg/kg/day, 2-generation rat reproduction study NOAEL
= 500 mg/kg/day and rat developmental study NOAEL = 1000 mg/kg/day
    An uncertainty factor (UF) of 100 was applied to account for inter-
(10x) and intra-(10x) species variation. The 10X factor to protect
infants and children as required by FQPA was removed, since there was
no special sensitivity for infants and children and the database is
complete.

    4. Carcinogenicity. EPA's Cancer Peer Review Committee classified
glyphosate as a "Group E" pesticide which shows no evidence for
carcinogenicity in rats and mice.

    A chronic feeding/carcinogenicity study in Sprague-Dawley rats was
performed at doses of 0, 30, 100, or 300 ppm (3, 10, or 31 mg/kg/day)
for males and 3, 14, or 34 mg/kg/day for females for 26 months. At the
high-dose, in comparison to concurrent controls, the following results
were observed: increased incidence of C-cell thyroid carcinomas in
females and an increased incidence of interstitial cell Leydig cell
testicular tumors. The thyroid tumors were not statistically
significant by pairwise comparison to controls and the testicular
tumors were within the range of historical controls for studies of
comparable duration. It was concluded that the study results were
negative for carcinogenicity, but that the dose levels were not high
enough to assess carcinogenic potential.
    A second chronic feeding/carcinogenicity study was conducted in
Sprague-Dawley rats for 24 months at dose levels of 2,000, 8,000, or
20,000 ppm (89, 362, or 940 mg/kg/day) for males and 113, 457, or 1,183
mg/kg/day in females. The results showed increased incidence of
pancreatic islet cell adenomas at the low and high dose in males,
hepatocellular adenomas at the low and high dose in males, and C-cell
thyroid adenomas in both sexes at the mid and high dose group. Each of
the tumor types was not considered treatment-related for the following
reasons:
    i. The pancreatic islet cell tumors had no statistically
significant dose-related trend, there was no progression to carcinomas,
and the incidence of pancreatic hyperplasia was not dose-related.
    ii. The hepatocellular adenomas were within the range of historical
controls, these liver tumors were not statistically significant by
pairwise comparison to concurrent controls, there was no progression to
carcinoma, and the incidence of hyperplasia was not considered
compound-related.
    iii. The C-cell thyroid tumors were not statistically significant
by pairwise comparison and positive dose-related trend, there was no
progression to carcinoma, and there was no statistically significant
dose-related increase in either incidence or severity of hyperplasia in
either sex.
    A carcinogenicity study in CD-1 mice was conducted for 24 months at
doses of 0, 150, 750, or 4,500 mg/kg/day (0, 1,000, 5,000, or 30,000
ppm). There were no effects at the low and mid-doses. At the high dose,
an increased incidence of renal tubular adenomas was seen in males, but
not in females zero incidence for all groups. In males, the incidence
was 1, 0, 1, and 3 out of 50/sex/dose. The occurrence of this rare
tumor was not statistically significant by pairwise comparison to
concurrent controls, but had a statistically significant dose-related
trend. There was no tumor associated non-neoplastic lesions in males,
but females had an increased incidence of proximal tubule epithelial
basophilia and hypertrophy in the absence of any renal tubular
neoplasms. In males, there was an increased incidence of interstitial
nephritis, hepatocellular hypertrophy and hepatocellular necrosis.
There was also statistically significant decreased weight gain in both
sexes. The high dose of 30,000 ppm exceeded the limit dose 7,000 ppm
for mice. The Agency concluded, based on a weight of the evidence
evaluation, that the renal tubular adenomas were not compound related
due to the absence of pairwise statistical significance for males, the
absence of related non-neoplastic lesion in males, and the presence of
related non-neoplastic lesions in females in the absence of renal
tubular adenomas. Additionally, the high dose exceeded the limit dose
required for testing in mice.

    5. Inhalation exposure general and long-term considerations.
Formulations of glyphosate are Toxicity Category III or IV and
technical glyphosate is a wetcake. The acute inhalation study was
waived for technical glyphosate. A dose and endpoint were not
identified for this risk assessment. This risk assessment is not
required.

C. Exposures and Risks

    1. From food and feed uses. Tolerances have been established (40
CFR 180.364) for the residues of glyphosate, in or on a variety of raw
agricultural commodities. Existing glyphosate tolerances are numerous
with values ranging from a low of 0.1 to a high of 200 ppm. Glyphosate
residues could possibly be transferred to meat and milk. However, in
feeding studies, no residues of glyphosate were found in milk or fat at
any dosing level and only minimal residues were found in eggs and
muscle (at the highest dose of 400 ppm). Significant residue levels
were found in animal liver and kidney, however, secondary residues are
not expected to exceed currently established animal tolerances. Risk
assessments were conducted by EPA to assessed dietary exposures from
glyphosate as follows:
     Dietary exposure to residues of a pesticide in a food commodity
are estimated by multiplying the average daily consumption of the food
forms of that commodity by the tolerance level or the anticipated
pesticide residue level. The Theoretical Maximum Residue Contribution
(TMRC) is an estimate of the level of residues consumed daily if each
food item contained pesticide residues equal to the tolerance. In
evaluating food exposures, EPA takes into account varying consumption
patterns of major identifiable subgroups of consumers, including
infants and children. The TMRC is a "worst case" estimate since it is
based on the assumptions that food contains pesticide residues at the
tolerance level and that 100% of the crop is treated by pesticides that
have established tolerances.
    The Agency's dietary risk evaluation system (DRES) analysis was
used for the chronic dietary exposure estimate for glyphosate. Using
permanent and time-limited tolerances, dietary exposure to residues of
glyphosate resulted in a TMRC equivalent to ≤ 3% of the RfD
for all population subgroups. No percent crop treated or anticipated
residue data were used in the analysis. By using the TMRC, the Agency
is reasonably certain that exposure is not underestimated for any
significant subpopulation. An uncertainty factor of 100 is used for all
subgroups. The proposed tolerances are for uses considered as Low
Dietary Intake (LDI) crops since the total acreage for all three crops
is less than 100 acres.
    i.  Acute exposure and risk. Acute dietary risk assessments are
performed for a food-use pesticide if a toxicological study has
indicated the possibility of an effect of concern occurring as a result
of a one day or single exposure. An acute dietary endpoint and dose was
not identified in the toxicology data base. A review of the rat and
rabbit developmental studies did not provide a dose or endpoint that
could be used for acute dietary risk purposes. Additionally, there were
no data requirements for acute or subchronic rat neurotoxicity studies
since there was no evidence of neurotoxicity in any of the toxicology
studies at very high doses.
    ii. Chronic exposure and risk. The chronic dietary exposure
analysis from food sources was conducted using the reference dose (RfD)
of 2.0 mg/kg/day. The RfD is based on the maternal NOAEL of 175 mg/kg/
day in female rabbits from the developmental study in rabbits, and an
uncertainty factor of 100 which is applicable to all population
subgroups.
    Durian, mangosteen, and rambutan all qualify as Low Dietary Intake
(LDI) crops since the total acreage for all three is less than 100
acres. Consequently, no data on these tropical fruits are included in
the current version of the DRES system. In conducting this chronic
dietary risk assessment, the Agency has assumed that inclusion of these
tropical fruits would not significantly change the resulting % RfD
values because glyphosate currently has tolerances on a large number of
non-LDI crops. In addition, EPA would note the exposure estimate for
existing tolerances is in an overestimate of human dietary exposure due
to the conservative assumptions built into the system.
    The existing glyphosate tolerances result in a TMRC that is
equivalent to the following percentages of the RfD:
    For subgroups, U.S. population (48 states), nursing infants (<1
year old) and non-nursing infants (<1 year old) the % RfD is 1.2, 1.2,
and 3.3, respectively. For the subgroups, children (1-6 years old),
children (7-12 years old), and males (13-19 years old) the % RfD is
2.6, 1.8, and 1.2, respectively.

    2. From drinking water. The GENEEC model and the SCI-GROW model
were run to produce estimates of glyphosate concentrations in surface
and ground water, respectively. The primary use of these models is to
provide a coarse screen for sorting out pesticides for which EPA has a
high degree of confidence that the true levels of the pesticide in
drinking water will be less than the human health drinking water levels
of concern (DWLOCs). A human health DWLOC is the concentration of a
pesticide in drinking water that would be acceptable as an upper limit
in light of total aggregate exposure to that chemical from food, water,
and non-occupational (residential) sources.
     DWLOCchronic is the concentration in drinking
water as part of the aggregate chronic exposure that results in a negligible
cancer risk. The Agency's default body weights and consumption values
used to calculate DWLOCs are as follows: 70 kg/2L(liter) (adult male),
60 kg/2L (adult female), and 10 kg/1L (child).
    i. Acute exposure and risk. An acute dietary endpoint and dose was
not identified in the toxicology data base. Adequate rat and rabbit
developmental studies did not provide a dose or endpoint that could be
used for acute dietary risk purposes. Additionally, there were no data
requirements for acute or subchronic rat neurotoxicity studies since
there was no evidence of neurotoxicity in any of the toxicology studies
at very high doses.
    The Agency concludes that no harm to public would result due to
acute risk for the proposed uses of glyphosate.
    ii. Chronic exposure and risk. For chronic (non-cancer) exposure to
glyphosate in surface and ground water, the drinking water levels of
concern are 69,000 μg/L for males (13 yrs+), 59,000 <greek-
m>g/L for females (13 yrs+) and 19,000 μg/L for children (1-6
yrs). To calculate the DWLOC for chronic (non-cancer) exposure relative to a
chronic toxicity endpoint, the chronic dietary food exposure (from
DRES) was subtracted from the RfD to obtain the acceptable chronic
(non-cancer) exposure to glyphosate in drinking water. DWLOCs were then
calculated using default body weights and drinking consumption figures.
    Estimated average concentrations of glyphosate in surface and
ground water are 0.063 ppb (after adjustment for the highly
conservative nature of the GENEEC model) and 0.0011 ppb, respectively.
The estimated average concentrations of glyphosate in surface and
ground water are less than EPA's level of concern for glyphosate in
drinking water as a contribution to chronic aggregate exposure.
Therefore, taking into account present uses and uses proposed in this
action, EPA concludes with reasonable certainty that residues of
glyphosate in drinking water (when considered along with other sources
of exposure for which EPA has reliable data) would not result in
unacceptable levels of aggregate human health risk at this time.

    3. From non-dietary exposure. Glyphosate is currently registered
for use on the following residential non-food sites: non-food crops and
a variety of other uses including ornamentals, greenhouses, residential
areas, lawns, and industrial rights of way. Glyphosate is formulated in
liquid and solid forms and it is applied using ground or aerial
equipment. Based on the registered uses of glyphosate, the potential
for occupational and residential exposures exists. However, based on
the low acute toxicity and the lack of other toxicological concerns,
glyphosate does not meet the Agency's criteria for occupational and
residential data requirements. The Agency believes that no significant
harm to public health would result due to non-dietary exposure from
proposed uses of glyphosate.
    i. Acute exposure and risk. There are no acute toxicological
concerns for glyphosate.
    ii. Chronic exposure and risk. Although there are registered
residential uses for glyphosate, glyphosate does not meet the Agency's
criteria for residential data requirements, due to the lack of
toxicological concerns. Incidental acute and/or chronic dietary
exposures from residential uses of glyphosate are not expected to pose
undue risks to the general population, including infants and children.
    iii. Short- and intermediate-term exposure and risk. EPA identified
no toxicological concerns for determined that short- intermediate- and
long-term dermal or inhalation routes of exposures. The Agency
concludes that exposures from residential uses of glyphosate are not
expected to pose undue risks.

    4. 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."
    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 a 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. For information regarding EPA's efforts to
determine which chemicals have a common mechanism of toxicity and to
evaluate the cumulative effects of such chemicals, see the Final Rule
for Bifenthrin Pesticide Tolerances November 26, 1997 (62 FR 62961)
(FRL 6023-5).

D. Aggregate Risks and Determination of Safety for U.S. Population

    1. Acute risk. There was no acute dietary endpoint identified,
therefore no acute toxicological concerns for glyphosate.

    2. Chronic risk. Using the TMRC exposure assumptions described
above, EPA has concluded that aggregate exposure to glyphosate from
food will utilize 1.2% of the RfD for the U.S. population. The major
identifiable subgroup with the highest aggregate exposure is non-
nursing infants less than 1 year old, which utilizes 3.3% of the RfD).
EPA generally has no concern 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 glyphosate in
drinking water and from non-dietary, non-occupational exposure, EPA
does not expect the aggregate exposure to exceed 100% of the RfD.

    3. Short- and intermediate-term risk. Short-term and intermediate-
term dermal and inhalation risk is not a concern due to the lack of
significant toxicological effects observed with glyphosate under these
exposure scenarios.
    Short- and intermediate-term aggregate exposure takes into account
chronic dietary food and water (considered to be a background exposure
level) plus indoor and outdoor residential exposure.

    4. Aggregate cancer risk for U.S. population. Glyphosate has been
classified as a Group E chemical, with no evidence of carcinogenicity
for humans in two acceptable animal studies.

    5. Determination of safety. Based on these risk assessments, EPA
concludes that there is a reasonable certainty that no harm will result
from aggregate exposure to glyphosate residues.

E. Aggregate Risks and Determination of Safety for Infants and Children

    1. Safety factor for infants and children--i. In general. In
assessing the potential for additional sensitivity of infants and
children to residues of glyphosate, EPA considered data from
developmental toxicity studies in the rat and rabbit and a 2-generation
reproduction study in the rat. The developmental toxicity studies are
designed to evaluate adverse effects on the developing organism
resulting from maternal pesticide exposure during gestation.
Reproduction studies provide information relating to effects from
exposure to the pesticide on the reproductive capability of mating
animals and data on systemic toxicity.
    FFDCA section 408 provides that EPA shall apply an additional
tenfold margin of 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 safety will be safe for infants and children. Margins of
safety are incorporated into EPA risk assessments either directly
through use of a margin of exposure (MOE) analysis or through using
uncertainty (safety) factors in calculating a dose level that poses no
appreciable risk to humans. EPA believes that reliable data support
using the standard uncertainty factor (usually 100 for combined inter-
and intra-species variability) and not the additional tenfold MOE/
uncertainty factor when EPA has a complete data base under existing
guidelines and when the severity of the effect in infants or children
or the potency or unusual toxic properties of a compound do not raise
concerns regarding the adequacy of the standard MOE/safety factor.
    ii. Developmental toxicity studies. In oral rat and rabbit
developmental studies and the oral rat reproduction study demonstrated
no indication of increased sensitivity of rats or rabbits to in utero
and postnatal exposure to glyphosate. In the rat developmental study,
the developmental NOAEL was 1,000 mg/kg/day and the maternal NOAEL was
1,000 mg/kg/day. Therefore, there was no prenatal developmental
toxicity in the absence of maternal toxicity. Similarly in rabbits, the
prenatal developmental NOAEL was 350 mg/kg/day and the maternal NOAEL
was 175 mg/kg/day. Therefore, prenatally exposed fetuses were not more
sensitive to the effects of glyphosate than maternal animals.
    iii. Reproductive toxicity study. In a rat reproduction study, the
parental NOAEL of 10,000 ppm was identical to the pup NOAEL of 10,000
ppm and decreased body weight was seen in both pup and parental
animals. This finding demonstrates that there are no extra
sensitivities with respect to pre- and post-natal toxicity between
adult and infant animals.
    iv. Pre- and post-natal sensitivity. The oral perinatal and
prenatal data demonstrated no indication of increased sensitivity of
rats or rabbits to in utero and postnatal exposure to glyphosate.
    v. Conclusion. There is a complete toxicity database for glyphosate
and exposure data are complete or estimated based on data that
reasonably accounts for potential exposures. Based on these data, there
is no indication that the developing fetus or neonate is more sensitive
than adult animals. No developmental neurotoxicity studies are being
required at this time. A developmental neurotoxicity data requirement
is an upper tier study and required only if effects observed in the
acute and 90-day neurotoxicity studies indicate concerns for frank
neuropathy or alterations seen in fetal nervous system in the
developmental or reproductive toxicology studies. The Agency believes
that reliable data support the use of the standard 100-fold uncertainty
factor, and that a tenfold (10x) uncertainty factor is not needed to
protect the safety of infants and children.

    2. Acute risk. Although there are no acute toxicological endpoints
for glyphosate, there exist an adequate exposure database to assess
potential adverse effects on infants and children, the most highly
exposed subgroup which utilize 3.3% of the RfD. The Agency concludes
that the establishment of the proposed tolerances would not pose an
unacceptable aggregate risk.

    3. Chronic risk. Using the exposure assumptions described above,
EPA has concluded that aggregate exposure to glyphosate from food will
utilize 3.3% of the RfD for infants and children. For the general
population, aggregate exposure to glyhosate from food is 1.2% of the
RFD. EPA generally has no concern 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 glyphosate in
drinking water and from non-dietary, non-occupational exposure, EPA
does not expect the aggregate exposure to exceed 100% of the RfD.

    4. Short- or intermediate-term risk. Short-term and intermediate-
term dermal and inhalation risk is not a concern due to the lack of
significant toxicological effects observed with glyphosate under these
exposure scenarios.

    5. Determination of safety. Based on these risk assessments, EPA
concludes that there is a reasonable certainty that no harm will result
to infants and children from aggregate exposure to glyphosate residues.

III. Other Considerations

A. Metabolism In Plants and Animals

    The qualitative nature of the residue in plants is adequately
understood. Studies with a variety of plants including corn, cotton, soybeans,
and wheat indicate that the uptake of glyphosate or its metabolite,
aminomethylphosphonic acid (AMPA), from soil is limited. The material which is
taken up is readily translocated. Foliarly applied glyphosate is readily
absorbed and translocated throughout the trees of vines to the fruit of
apples, coffee, dwarf citrus (calamondin), pears and grapes. Metabolism via N-
methylation yields N-methylated glycines and phosphonic acids. For the
most part, the ratio of glyphosate to AMPA is 9 to 1 but can approach 1
to 1 in a few cases (e.g., soybeans and carrots). Much of the residue
data for crops reflects a detectable residue of parent (0.05 - 0.15
ppm) along with residues below the level of detection (< 0.05 ppm) of
AMPA. The terminal residue to be regulated in plants is glyphosate per
se.
    The qualitative nature of the residue in animals is adequately
understood. Studies with lactating goats and laying hens fed a mixture
of glyphosate and AMPA indicate that the primary route of elimination
was by excretion (urine and feces). These results are consistent with
metabolism studies in rats, rabbits, and cows. The terminal residues in
eggs, milk, and animal tissues are glyphosate and its metabolite AMPA;
there was no evidence of further metabolism. The terminal residue to be
regulated in livestock is glyphosate per se.

B. Analytical Enforcement Methodology

    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 fluorometric detection.
Use of the GLC method is discouraged due to the lengthiness of the
experimental procedure. The HPLC procedure has undergone successful
Agency validation and was recommended for inclusion in PAM II. A GC/MS
method for glyphosate in crops has also been validated by EPA's
Analytical Chemistry Laboratory (ACL).
    Adequate analytical methods are available for residue data
collection and enforcement of the proposed tolerances of glyphosate in
or on durian, mangosteen, and rambutan.

C. Magnitude of Residues

    Residue studies for glyphosate were not submitted for review with
this petition. However, the Agency believes that data submitted
previously in support of petitions may be used to support proposed
uses.
    The proposed use for glyphosate is for orchard floor treatment. The
registrant referenced extensive experience and data with glyphosate in/
on tree fruit and nuts crops which show that when orchard floor
applications are made, no detectable residues of the herbicide are
recovered in the harvested fruit. Based on these data EPA expects no
detectable residues of glyphosate in durian, mangosteen or rambutan
when glyphosate is applied in a similar manner. Glyphosate is known to
be a water soluble chemical and does not rapidly transport into trees
from soil. Residues are expected to be mainly due to contamination
(e.g., spray drift). Therefore, significant amounts of residues are not
expected to be detected in tree crops.
    Tolerances for the combined residues of glyphosate and its
metabolite, aminomethylphosphonic acid (AMPA), have been established at
0.2 ppm on a number of tree fruit and nuts, as well as a variety of
tropical fruit: acerola, atemoya, avocado, banana, breadfruit,
canistel, carambola, cherimoya cocoa beans, coconuts, dates, figs,
genip, jaboticaba, jackfruit, longan, lychee, mango, mayhaw, passion
fruit, persimmon, pomegranate, sapodilla, sapote, soursop, sugar apple
and tamarind. Any secondary residues occurring in milk, eggs, meat,
fat, liver and kidney of cattle, goats, horses, hogs, poultry and sheep
are covered by existing tolerances.
    EPA has determined that AMPA should be dropped from the tolerance
expression. Tolerances that are the subject of this notice are based
solely on residues of glyphosate.

D. International Residue Limits

    There are no CODEX, Canadian, or Mexican tolerances for glyphosate
residues on durian, mangosteen, or rambutan. Therefore, international
harmonization is not an issue at this time.

IV. Conclusion

    Therefore, the tolerance is established for residues of glyphosate
N-(phosphonomethyl) glycine in durian commodity at 0.2 ppm, mangosteen
at 0.2 ppm, and rambutan at 0.2 ppm.

V. 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
new section 408(e) and (l)(6) as was provided in the old section 408
and in section 409. However, the period for filing objections is 60
days, rather than 30 days. EPA currently has procedural regulations
which govern 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 may, by December 7, 1998, file written objections to any
aspect of this regulation and may also request a hearing on those
objections. Objections and hearing requests must be filed with the
Hearing Clerk, at the address given above (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 or a fee waiver
request as specified prescribed by 40 CFR 180.33. If a hearing is
requested, the objections must include a statement of the factual
issues on which a hearing is requested, the requestor's contentions on
such issues, and a summary of any evidence relied upon by the requestor
(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 genuine and substantial issue of fact; there is a
reasonable possibility that available evidence identified by the
requestor would, if established, resolve one or more of such issues in
favor of the requestor, taking into account uncontested claims or facts
to the contrary; and resolution of the factual issues 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
part or all of that information as Confidential Business Information
(CBI). Information so marked 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.

VI. Public Record and Electronic Submissions

    EPA has established a record for this rulemaking under docket
control number OPP-300736 (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
119 of the Public Information and Records Integrity Branch, Information
Resources and Services Division (7502C), Office of Pesticide Programs,
Environmental Protection Agency, Crystal Mall #2, 1921 Jefferson Davis Hwy.,
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
Virginia address in "ADDRESSES" at the beginning of this document.

VII. Regulatory Assessment Requirements

A. Certain Acts and Executive Orders

    This final rule establishes tolerances under FFDCA section 408(d)
in response to a petition submitted to the Agency. The Office of
Management and Budget (OMB) has exempted these types of actions from
review under Executive Order 12866, entitled Regulatory Planning and
Review (58 FR 51735, October 4, 1993). This final rule does not contain
any information collections subject to OMB approval under the Paperwork
Reduction Act (PRA), 44 U.S.C. 3501 et seq., or impose any enforceable
duty or contain any unfunded mandate as described under Title II of the
Unfunded Mandates Reform Act of 1995 (UMRA) (Pub. L. 104-4). Nor does
it require any prior consultation as specified by Executive Order
12875, entitled Enhancing the Intergovernmental Partnership (58 FR
58093, October 28, 1993), or special considerations as required by
Executive Order 12898, entitled Federal Actions to Address
Environmental Justice in Minority Populations and Low-Income
Populations (59 FR 7629, February 16, 1994), or require OMB review in
accordance with Executive Order 13045, entitled Protection of Children
from Environmental Health Risks and Safety Risks (62 FR 19885, April
23, 1997).
    In addition, since tolerances and exemptions that are established
on the basis of a petition under FFDCA section 408(d), such as the
[tolerances /exemption] in this final rule, do not require the issuance
of a proposed rule, the requirements of the Regulatory Flexibility Act
(RFA) (5 U.S.C. 601 et seq.) do not apply. Nevertheless, the Agency has
previously assessed whether establishing tolerances, exemptions from
tolerances, raising tolerance levels or expanding exemptions might
adversely impact small entities and concluded, as a generic matter,
that there is no adverse economic impact. The factual basis for the
Agency's generic certification for tolerance actions published on May
4, 1981 (46 FR 24950) and was provided to the Chief Counsel for
Advocacy of the Small Business Administration.

B. Executive Order 12875

    Under Executive Order 12875, entitled Enhancing the
Intergovernmental Partnership (58 FR 58093, October 28, 1993), EPA may
not issue a regulation that is not required by statute and that creates
a mandate upon a State, local, or tribal government, unless the Federal
government provides the funds necessary to pay the direct compliance
costs incurred by those governments. If the mandate is unfunded, EPA
must provide to OMB a description of the extent of EPA's prior
consultation with representatives of affected State, local, and tribal
governments, the nature of their concerns, copies of any written
communications from the governments, and a statement supporting the
need to issue the regulation. In addition, Executive Order 12875
requires EPA to develop an effective process permitting elected
officials and other representatives of State, local, and tribal
governments "to provide meaningful and timely input in the development
of regulatory proposals containing significant unfunded mandates."
    Today's rule does not create an unfunded Federal mandate on State,
local, or tribal governments. The rule does not impose any enforceable
duties on these entities. Accordingly, the requirements of section 1(a)
of Executive Order 12875 do not apply to this rule.

C. Executive Order 13084

    Under Executive Order 13084, entitled Consultation and Coordination
with Indian Tribal Governments (63 FR 27655, May 19,1998), EPA may not
issue a regulation that is not required by statute, that significantly
or uniquely affects the communities of Indian tribal governments, and
that imposes substantial direct compliance costs on those communities,
unless the Federal government provides the funds necessary to pay the
direct compliance costs incurred by the tribal governments. If the
mandate is unfunded, EPA must provide to OMB, in a separately
identified section of the preamble to the rule, a description of the
extent of EPA's prior consultation with representatives of affected
tribal governments, a summary of the nature of their concerns, and a
statement supporting the need to issue the regulation. In addition,
Executive Order 13084 requires EPA to develop an effective process
permitting elected officials and other representatives of Indian tribal
governments "to provide meaningful and timely input in the development
of regulatory policies on matters that significantly or uniquely affect
their communities."
    Today's rule does not significantly or uniquely affect the
communities of Indian tribal governments. This action does not involve
or impose any requirements that affect Indian tribes. Accordingly, the
requirements of section 3(b) of Executive Order 13084 do not apply to
this rule.

VIII. Submission to Congress and the Comptroller General

    The Congressional Review Act, 5 U.S.C. 801 et seq., as added by the
Small Business Regulatory Enforcement Fairness Act of 1996, generally
provides that before a rule may take effect, the agency promulgating
the rule must submit a rule report, which includes a copy of the rule,
to each House of the Congress and to the Comptroller General of the
United States. EPA will submit 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 United States prior
to publication of the rule in the Federal Register. This rule is not a
"major rule" as defined by 5 U.S.C. 804(2).

List of Subjects in 40 CFR Part 180

    Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.

    Dated: September 29, 1998.

James Jones,
Director, Registration Division, Office of Pesticide Programs.

    Therefore, 40 CFR chapter I is amended as follows:

PART 180-[AMENDED]

    1. The authority citation for part 180 continues to read as
follows:

    Authority: 21 U.S.C. 346a and 371.

    2. In Sec.  180.364, paragraph (a), by designating the text
following the paragraph heading as paragraph (a)(1), and by adding
paragraph (a)(2) to read as follows:

Sec.  180.364   Glyphosate; residues for tolerances.

    (a) *    *    *
    (2) Tolerances are established for residues of glyphosate N-
(phosphonomethyl) glycine in or on the commodities list in the table as
follows:

------------------------------------------------------------------------
                                                                  Parts
                           Commodity                               per
                                                                 million
------------------------------------------------------------------------
Durian.........................................................    0.2
Mangosteen.....................................................    0.2
Rambutan.......................................................    0.2
------------------------------------------------------------------------

*    *    *    *    *

[FR Doc. 98-26906 Filed 10-7-98; 8:45 am]
BILLING CODE 6560-50-F