[Federal Register Volume 63, Number 176 (Friday, September 11, 1998)]
[Rules and Regulations]
[Pages 48597-48607]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-24468]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Parts 180 and 185
[OPP-300709; FRL 6026-6]
RIN 2070-AB78
Sulfosate; Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This regulation establishes new tolerances to replace
recently-expired time-limited tolerances for residues of the herbicide
sulfosate (the trimethylsulfonium salt of glyphosate, also known as
glyphosate-trimesium) in or on cattle, goats, horses, hogs and sheep,
in fat, meat by-products, and meat; in poultry fat, meat-by-products
(except liver), meat and liver; in eggs; in milk; in corn stover (field
and pop), grain (field and pop), and forage (field); in soybean forage,
hay, and seed; and in aspirated grain fractions. Zeneca Ag Products
requested these tolerances under the Federal Food, Drug, and Cosmetic
Act (FFDCA), as amended by the Food Quality Protection Act of 1996
(Pub. L. 104-170). In addition, this regulation moves existing
tolerances for prunes at 0.20 ppm, raisins at 0.20 ppm, and soybean
hulls at 7.0 ppm from 40 CFR 185.5375 to 40 CFR 180.489.
DATES: This regulation is effective September 11, 1998. Objections and
requests for hearings must be received by EPA on or before November 10,
1998.
ADDRESSES: Written objections and hearing requests, identified by the
docket control number, OPP-300709, 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-300709, 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, CM #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: [email protected]. 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-
300709. 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: Jim Tompkins, 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, 703-305-5697; e-mail:
[email protected].
[[Page 48598]]
SUPPLEMENTARY INFORMATION: In the Federal Register of March 8, 1996 (61
FR 9355) (FRL 5353-4), time-limited tolerances were established for
sulfosate on corn and animal commodities (listed below). In the Federal
Register of April 10, 1996 (61 FR 15899) (FRL 5782-9), time-limited
tolerances were established for unprocessed soybean commodities and
aspirated grain fractions (listed below).
In the Federal Register of March 4, 1998 (63 FR 10614) (FRL 5772-
6), 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 for tolerance by Zeneca Ag Products, 1800
Concord Pike, P. O. Box 15458, Wilmington, DE 19850-5458. This notice
included a summary of the petition prepared by Zeneca Ag Products, the
registrant. There were no comments received in response to the notice
of filing.
The petition 0F3860 requested that 40 CFR 180.489 be amended by
removing the expiration date of April 10, 1998, for residues of the
herbicide sulfosate (glyphosate-trimesium; sulfonium, trimethyl salt
with N- (phosphonomethyl)glycine (1:1)), in or on soybean forage (2.00
ppm, of which no more than 1 ppm is trimethylsulfonium (TMS)), soybean
aspirated grain fractions (210.00 ppm, of which no more than 60 ppm is
TMS), soybean hay (5.00 ppm, of which no more than 2 ppm is TMS), and
soybean seed (3.00 ppm of which no more than 1 ppm is TMS). The
petition 9F3796 requested that 40 CFR 180.489 be amended by removing
the expiration date of March 9, 1998 for residues of sulfosate in or on
cattle, goat, hog, horse, sheep and poultry fat (0.10 ppm), meat by
products (1.00 ppm), and meat (0.20 ppm); poultry liver (0.05 ppm),
poultry meat by-products (0.10 ppm), and poultry meat (0.05 ppm); corn
fodder (0.30, of which no more than 0.20 is trimethylsulfonium TMS)),
corn forage (0.10 ppm), and corn grain (0.20 ppm, of which no more than
0.10 ppm is TMS); milk (0.20 ppm); and eggs (0.02 ppm).
In the corn tolerances for this action, the commodity term
``stover'' replaces the older term ``fodder'' in keeping with current
EPA policy for naming this commodity. In this action, the previous
tolerance for ``soybean aspirated grain fractions'' is replaced with
the tolerance for ``aspirated grain fractions''. The term ``soybean
aspirated grain fractions'' was printed in error in the April 10, 1996
FR notice (61 FR 15899); aspirated grain fractions typically contain
more than one type of grain and typically contain both soybeans and
corn.
This action also moves tolerances for prunes, raisins, and soybean
hulls from 40 CFR 185.5375 to 40 CFR 180.489. The Food Quality
Protection Act (FQPA) amended the Federal Food, Drug and Cosmetic Act
(FFDCA) to consolidate pesticide tolerances for raw and processed
agricultural commodities under FFDCA section 408(j)(2). Prior to this
change, raw agricultural commodity tolerances were established
according to FFDCA section 408 and processed commodities were
established according to FFDCA section 409. As a result of the change
in the regulations governing FFDCA, all new tolerances for both raw and
agricultural commodities are established according to FFDCA section
408(j)(2) in 40 CFR part 180. When 40 CFR part 180 is amended as to a
specific pesticide, it is EPA's policy to move existing related
regulations governing residues of that pesticide on processed
agricultural commodities from 40 CFR parts 185 and 186 and place them
in part 180. Ultimately, EPA will amend all tolerance regulations so
that all tolerances are listed in 40 CFR part 180.
I. Risk Assessment and Statutory Findings
New 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. First, EPA determines the
toxicity of pesticides based primarily on toxicological studies using
laboratory animals. These studies address many adverse health effects,
including (but not limited to) reproductive effects, developmental
toxicity, toxicity to the nervous system, and carcinogenicity. Second,
EPA examines exposure to the pesticide through the diet (e.g., food and
drinking water) and through exposures that occur as a result of
pesticide use in residential settings.
A. Toxicity
1. Threshold and non-threshold effects. For many animal studies, a
dose response relationship can be determined, which provides a dose
that causes adverse effects (threshold effects) and doses causing no
observed effects (the ``no-observed effect level'' or ``NOEL'').
Once a study has been evaluated and the observed effects have been
determined to be threshold effects, EPA generally divides the NOEL from
the study with the lowest NOEL by an uncertainty factor (usually 100 or
more) to determine the Reference Dose (RfD). The RfD is a level at or
below which daily aggregate exposure over a lifetime will not pose
appreciable risks to human health. An uncertainty factor (sometimes
called a ``safety factor'') of 100 is commonly used since it is assumed
that people may be up to 10 times more sensitive to pesticides than the
test animals, and that one person or subgroup of the population (such
as infants and children) could be up to 10 times more sensitive to a
pesticide than another. In addition, EPA assesses the potential risks
to infants and children based on the weight of the evidence of the
toxicology studies and determines whether an additional uncertainty
factor is warranted. Thus, an aggregate daily exposure to a pesticide
residue at or below the RfD (expressed as 100% or less of the RfD) is
generally considered acceptable by EPA. EPA generally uses the RfD to
evaluate the chronic risks posed by pesticide exposure. For shorter
term risks, EPA uses a RfD approach or calculates a margin of exposure
(MOE) by dividing the estimated human exposure into the NOEL from the
appropriate animal study. Commonly, EPA finds MOEs lower than 100 to be
unacceptable. This 100-fold MOE is based on the same rationale as the
100-fold uncertainty factor.
Lifetime feeding studies in two species of laboratory animals are
conducted to screen pesticides for cancer effects. When evidence of
increased cancer is noted in these studies, the Agency conducts a
weight of the evidence review of all relevant toxicological data
including short-term and mutagenicity studies and structure activity
relationship. Once a pesticide has been classified as a potential human
carcinogen, different types of risk assessments (e.g., linear low dose
extrapolations or MOE calculation based
[[Page 48599]]
on the appropriate NOEL) will be carried out based on the nature of the
carcinogenic response and the Agency's knowledge of its mode of action.
2. Differences in toxic effect due to exposure duration. The
toxicological effects of a pesticide can vary with different exposure
durations. EPA considers the entire toxicity data base, and based on
the effects seen for different durations and routes of exposure,
determines which risk assessments should be done to assure that the
public is adequately protected from any pesticide exposure scenario.
Both short and long durations of exposure are always considered.
Typically, risk assessments include ``acute,'' ``short-term,''
``intermediate term,'' and ``chronic'' risks. These assessments are
defined by the Agency as follows.
Acute risk, by the Agency's definition, results from 1-day
consumption of food and water, and reflects toxicity which could be
expressed following a single oral exposure to the pesticide residues.
High end exposure to food and water residues are typically assumed.
Short-term risk results from exposure to the pesticide for a period
of 1-7 days, and therefore overlaps with the acute risk assessment.
Historically, this risk assessment was intended to address primarily
dermal and inhalation exposure which could result, for example, from
residential pesticide applications. However, since enaction of FQPA,
this assessment has been expanded to include both dietary and non-
dietary sources of exposure, and will typically consider exposure from
food, water, and residential uses when reliable data are available. In
this assessment, risks from average food and water exposure, and high-
end residential exposure, are aggregated. High-end exposures from all
three sources are not typically added because of the very low
probability of this occurring in most cases, and because the other
conservative assumptions built into the assessment assure adequate
protection of public health. However, for cases in which high-end
exposure can reasonably be expected from multiple sources (e.g.
frequent and widespread homeowner use in a specific geographical area),
multiple high-end risks will be aggregated and presented as part of the
comprehensive risk assessment/characterization. Since the toxicological
endpoint considered in this assessment reflects exposure over a period
of at least 7 days, an additional degree of conservatism is built into
the assessment; i.e., the risk assessment nominally covers 1-7 days
exposure, and the toxicological endpoint/NOEL is selected to be
adequate for at least 7 days of exposure. (Toxicity results at lower
levels when the dosing duration is increased.)
Intermediate-term risk results from exposure for 7 days to several
months. This assessment is handled in a manner similar to the short-
term risk assessment.
Chronic risk assessment describes risk which could result from
several months to a lifetime of exposure. For this assessment, risks
are aggregated considering average exposure from all sources for
representative population subgroups including infants and children.
B. Aggregate Exposure
In examining aggregate exposure, FFDCA section 408 requires that
EPA take into account available and reliable information concerning
exposure from the pesticide residue in the food in question, residues
in other foods for which there are tolerances, residues in groundwater
or surface water that is consumed as drinking water, and other non-
occupational exposures through pesticide use in gardens, lawns, or
buildings (residential and other indoor uses). 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. If the TMRC exceeds the RfD or poses a lifetime
cancer risk that is greater than approximately one in a million, EPA
attempts to derive a more accurate exposure estimate for the pesticide
by evaluating additional types of information (anticipated residue data
and/or percent of crop treated data) which show, generally, that
pesticide residues in most foods when they are eaten are well below
established tolerances.
Percent of crop treated estimates are derived from federal and
private market survey data. Typically, a range of estimates are
supplied and the upper end of this range is assumed for the exposure
assessment. By using this upper end estimate of percent of crop
treated, the Agency is reasonably certain that exposure is not
understated for any significant subpopulation group. Further, regional
consumption information is taken into account through EPA's computer-
based model for evaluating the exposure of significant subpopulations
including several regional groups, to pesticide residues. For this
pesticide, the most highly exposed population subgroups (females,
infants, and children) were not regionally based.
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 sulfosate
and to make a determination on aggregate exposure, consistent with
section 408(b)(2), for tolerance for residues of sulfosate on cattle,
goats, horses, hogs and sheep at 0.10 ppm in fat, at 1.00 ppm in meat
by-products, and at 0.20 ppm in meat; in poultry at 0.05 ppm in fat,
meat-by-products (except liver), and meat, and at 0.10 ppm in liver; in
eggs at 0.02 ppm; in milk at 0.20 ppm; in corn at 0.30 ppm (of which no
more than 0.20 ppm is TMS) in stover (field and pop), at 0.20 ppm (of
which no more than 0.10 ppm is TMS) in grain (field and pop), at 0.10
ppm in forage (field); in soybeans at 2.00 ppm (of which no more than
1.0 ppm is TMS) in forage, at 5.00 ppm (of which no more than 2.0 ppm
is TMS) in hay, and at 3.00 (of which no more than 1.0 ppm is TMS) ppm
in seed; and in aspirated grain fractions at 210 ppm (of which no more
than 60 ppm is TMS). EPA's assessment of the dietary exposures and
risks associated with establishing the tolerance 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 sulfosate are
discussed below.
Several acute toxicity studies were performed, placing technical-
grade sulfosate in Toxicity Category III. The acute toxicity data for
sulfosate show that this chemical is not acutely toxic by the oral,
inhalation, and dermal routes
[[Page 48600]]
of exposure. Sulfosate technical is, however, a slight dermal
sensitizer.
In a subchronic feeding study, 6 week old CrL: CD(SD)BR Sprague-
Dawley rats were treated with Sulfosate technical at doses of 0, 150,
350, 800 or 2,000 ppm sulfosate in their diet (males for 90 days &
females for 96 days). At 2,000 ppm in males (88 mg/kg/day) there was a
significant overall decrease in body weight gain of 22%. At 2,000 ppm,
the females exhibited some sporadic and minimal decreases in body
weight (6% at week 2, 8% at week 11, 21% at week 13) which were due to
a decrease in food consumption and is not used to set a lowest effect
level (LOEL). No significant changes were observed in clinical
chemistry, hematology, clinical observations, organ weight, and
macroscopic/microscopic histopathology. The systemic no effect level
(NOEL) is 800 ppm in males (36 mg/kg/day) and 2,000 ppm (108 mg/kg/day)
in females. The systemic LOEL is 2,000 ppm in males (88 mg/kg/day),
based on significant overall decrease in body weight gain of 22%. The
maximum tolerated dose (MTD) was achieved only in male rats.
Two subchronic toxicity studies on dogs were conducted. In one
subchronic oral study, beagle dogs were treated with Sulfosate
technical at doses of 0, 2, 10 or 50 mg/kg/day. The dose volume was 0.5
milliliter per kilogram body weight (ml/kg b.w.) by oral gavage (5
days/week) for 45-50 days. The NOEL is 10 mg/kg/day for both males and
females. The LOEL is 50 mg/kg/day for both males and females, based on
significant earlier onsets and increased incidence of salivation and
emesis. No significant change was observed in body weight, food
consumption, urinalysis, organ weights, macroscopic/microscopic
histopathology, hematology, and clinical chemistry including
cholinesterase activity. In another subchronic toxicity study,
Sulfosate was administered to 4 male and 4 female beagle dogs by
gelatin capsule at doses of 0, 10, 25, or 50 mg/kg/day for at least 90
days. Evaluations included clinical observations, body weight, food
consumption, clinical pathology, organ weights and gross and
microscopic histopathology. There were no effects on food consumption,
body weight, clinical pathology, organ weights or histopathology.
Observed at 50 mg/kg/day in both sexes was salivation at dosing (weeks
2-14) and/or salivation (weeks 1-13) either consistently or
intermittently, and resisting dosing (weeks 6-13) occasionally. A
female in the 50 mg/kg/day group was sacrificed on day 2 after being
found cold and recumbent and replaced with another female dog. The dose
was lowered to 40 mg/kg/day in another female dog (50 mg/kg/day group)
for most of the remainder of the study following two incidents of
tremors, recumbency, and voluntary paddling of the limbs. One high dose
male had a unilateral cataract. The LOEL is 50 mg/kg/day, based on
clinical signs of neurotoxicity in the females. The NOEL is 25 mg/kg/
day.
Two 21-day dermal studies were conducted. In one 21-day dermal
study, Rabbits (New Zealand White) were treated with sulfosate soluble
concentrate (51.2% a.i.), Sulfosate at doses of 0, 10, 100, 1,000 mg/
kg/day, 6 hrs/day, 5 days/wk for 3 weeks. There was no systemic
toxicity at any dose. There was mild erythema at application sites in
all sulfosate-treated groups. The systemic NOEL is 1,000 mg/kg/day, the
highest dose tested (HDT). In another 21-day dermal study, sulfosate
emulsifiable concentrate (39.8% a.i.) was applied to the skin of rats
(Alpk: AP (Wistar derived), 5/sex/group) at doses of 25, 250, 1,000 mg/
kg in 0.0021, 0.027, and 0.0826 ml/100 g body wt. At 25 and 1,000 mg/
kg/day (not 250 mg/kg/day) there was a slight increase in testes weight
with normal histology (toxicological significance is unclear). There
was occasional sciatic nerve fiber degeneration (1 male and 2 females
out of a total of 10) at 1,000 mg/kg/day. There was occasional sciatic
nerve fiber degeneration (1/5 males, 2/5 females) at 1,000 mg/kg/day
with none in controls. Dermal irritation occurred in male rats at 1,000
mg/kg/day including scabbing, erythema, edema and desquamation. There
were no histological changes. The systemic LOEL was 1,000 mg/kg/day
based on sciatic nerve findings. The NOEL was 250 mg/kg/day.
In a feeding/carcinogenicity study, 60/sex/group Sprague-Dawley
(Crl: CD SD BR) rats were tested with sulfosate soluble concentrate
(56.2% a.i.) at dose levels of 0 (basal diet, no vehicle), 0 (basal
diet plus 1% propylene glycol), 100, 500 or 1,000 ppm a.i. (male - 0,
4.2, 21.2, or 41.8; female - 0, 5.4, 27.0, or 55.7) for 2 years. Rats
may have tolerated higher dose levels. At 1,000 ppm there were
decreases in bodyweight in both males and females and an increase in
incidences of chronic laryngeal and nasopharyngeal inflammation in
males. Bodyweight decrease was secondary to the decrease in food
consumption. The LOEL and NOEL were at or above 1,000 ppm (41.8 and
55.7 mg/kg/day for males and females, respectively). There was no
evidence of carcinogenicity in this study at the doses tested. The
study is considered acceptable based on the results of a subchronic and
reproduction study. The high dose for a feeding/carcinogenicity study
should be near, but not necessarily at, a dose that would produce well
defined toxicity. The subchronic rat study indicated well defined
toxicity at 2,000 ppm (only twice the high dose in the feeding/
carcinogenicity study), a dose that is adequate for estimating a
maximum tolerated dose (MTD). Therefore, 1,000 ppm in the feeding/
carcinogenicity study is considered a reasonable extrapolation from the
subchronic toxicity study results. In addition, at 2,000 ppm in the
reproduction study there is well defined toxicity with some evidence of
toxicity, although less severe, at 800 ppm. Therefore, it is believed
that sulfosate was adequately tested for carcinogenicity in the rat.
In a chronic oral gavage study, beagle dogs (5/sex/dose) were
treated with sulfosate soluble concentrate (56.2% a.i.) for 1 year at
doses of 0, 2, 10, or 50 mg kg/day. Signs of toxicity were limited to
the 50 mg/kg/day group females and included transient salivation (1/5
at 10 mg/kg/day and 5/5 at 50 mg/kg/day) and emesis (single episodes in
3/5 dogs). The decreased lactic acid dehydrogenase (LDH) in females at
12 months is of questionable biological significance. The high dose was
however, supported by subchronic studies where transient salivation and
emesis again occurred at 50 mg/kg/day in a 90 day study and at 75 mg/
kg/day in a 28 day study; with death occurring within 3 days at 150 mg/
kg/day in the 28 day study. The LOEL is 50 mg/kg/day based on
salivation and emesis and support from shorter term studies also with
emesis and salivation. The NOEL is 10 mg/kg/day.
In a feeding carcinogenicity study, mice (60/sex/dose) were given
sulfosate technical ( 56.17% a.i.) in the diet at concentrations of 0a
(dietary control), 0b (vehicle control), 100, 1,000 and 8,000 ppm
(males at 0, 0, 11.7, 118, or 991 mg/kg/day; and females at 0, 0, 16.0,
159, or 1,341 mg/kg/day) for 2 years. The only signs of toxicity
occurred at 8,000 ppm and included (in both sexes) decreased body
weight (about 10% lower than controls) and weight gain (about 50% lower
than controls). Decreased food consumption (0 to 15% lower than
controls in both sexes) was responsible only in part for the decreased
weight gain. In addition, there was increased incidence of white matter
degeneration in the lumbar region of the spinal cord (males only) (2,
3, 4, 4, 79% response, controls to high dose), and increased incidence
of epithelial hyperplasia of duodenum (females only) (10, 13, 16, 15,
24%
[[Page 48601]]
response, controls to high dose). The systemic LEL is 8,000 ppm (991,
1,340 mg/kg/day for males and females) based on decreased body weight &
food consumption (both sexes), increased incidence of white matter
degeneration in lumbar bar region of spinal cord (males only), and
increased incidence of epithelial hyperplasia of duodenum (females
only). The systemic NOEL is 1000 ppm (118, 159 mg/kg/day for males and
females). This study was tested to adequate doses based on decreased
body weight and weight gain. There was no evidence of carcinogenicity
in this study at the doses tested.
In a developmental toxicity study, rats (25/dose) were treated with
sulfosate soluble concentrate (19.2% a.i.) by gavage on gestation days
6 through 20 at dose levels of 0, 30, 100, or 333 mg/kg/day. The test
material was dissolved in water and administered in a volume of 5 ml/
kg. Treatment related effects were limited to the high dose dams and
included decreased body weight (17% less than the control), body weight
gain and feed consumption. There was also salivation, chromorhinorrhea
and lethargy after dosing in this group (p < 0.05). The Maternal LOEL
is 333 mg/kg/day based on decreased body weight, feed consumption and
body weight gain along with increased incidences of salivation,
chromorhinorrhea, and lethargy after dosing. The Maternal NOEL is 100
mg/kg/day. Developmental signs of toxicity were limited to the high
dose and included decreased fetal body weight (5.0, 4.9, 4.9, 4.2 gm,
controls to high dose). The Developmental toxicity LOEL is 333 mg/kg/
day based on decreased fetal body weight. The Developmental toxicity
NOEL is 100 mg/kg/day.
In a developmental toxicity study, New Zealand white rabbits (15/
group except 21 at the high dose) were treated by gavage with sulfosate
soluble concentrate (56.2% ai) from gestation days 7-19. The test
material was dissolved in water and administered in a volume of 2 ml/kg
at dose levels of 0, 10, 40 or 100 mg/kg/day. The Maternal LOEL is 100
mg/kg/day (6 deaths in 17 pregnant does, 4 abortions in the 11
survivors along with decreased body weight, feed consumption and body
weight gain). The Maternal NOEL is 40 mg/kg/day. The developmental LOEL
is 100 mg/kg/day based on decreased number of live fetuses/doe for 7
surviving rabbits (5.4 versus 7.4 in controls), 4 rabbits aborted their
litters. Having only 7 litters does not give a sufficiently high number
of animals to absolutely conclude that no developmental toxicity is
occurring, particularly in light of the massive losses to death and
abortions. The developmental NOEL is 40 mg/kg/day.
In a 2-generation reproduction study, 20 male and 30 female/group
Sprague-Dawley rats received sulfosate soluble concentrate (19.2% a.i.)
at dose levels of 0, 150, 800, or 2,000 ppm in the diet (average for
P0 and P1 - males - 0, 6.0, 35, 88.5 mg/kg/day;
females - 0, 8, 41, 98 mg/kg/day). The systemic LEL is 800 ppm (35 and
41 mg/kg/day for males and females) based on a decrease in absolute and
sometimes relative organ weights in both generations (thymus, heart,
kidney and liver) at 800 and 2,000 ppm and a decrease in body weights
and body weight gains during the premating period at 2,000 ppm. The
Systemic NOEL is 150 ppm (6 and 8 mg/kg/day for males and females). The
reproductive/developmental LOEL is 800 ppm (35 and 41 mg/kg/day for
males and females) is based on decreased litter size in F0a
and F1b litters at 2,000 ppm and on decrease in mean pup
weights during lactation in second litters at 800 ppm & in all litters
at 2,000 ppm. The reproductive/developmental NOEL is 150 ppm (6 and 8
mg/kg/day for males and females).
In an acute neurotoxicity study, white leghorn chickens (6 hens/
group in control groups, 8 hens/group in treated groups) were treated
with technical sulfosate (56.9% a.i.) by gavage at doses of 0, 500 or
5,000 mg/kg in 5 ml/kg water. Tri-ortho-cresylphosphate (TOCP, 500 mg/
kg) was the positive control. Each animal was dosed twice during study;
day 1 and day 22. Each animal was evaluated up to day 41 (or 42). At
500 mg/kg there was diarrhea starting a few days after each dosing,
lasting for 2-3 days. At 5,000 mg/kg there was diarrhea, changes in
comb appearance, early decreased food consumption and decrease in egg
production. No indications of neurotoxicity were observed. The positive
control indicated the appropriate clinical sings of toxicity, increased
ataxia and microscopic observations for an organophosphate. The NOEL
for systemic toxicity was 500 mg/kg. The LEL for systemic toxicity was
5,000 mg/kg.
In an acute neurotoxicity study, sulfosate technical (59.4% a.i.)
was used to treat Alpk: APfsD rats, 10/sex/dose by gavage at 1 ml/100 g
bw with doses of 0, 30, 100 or 300 mg/kg. Adequate positive control
data were provided. At 300 mg/kg there was death, ptosis, decreased
activity, decreased splay reflex, upward curvature of spine,
chromodacryorrhea, staining around the nose, decreased bodyweight and
food consumption (males), shaking, sides pinched in, signs of urinary
incontinence, irregular breathing, hunched posture, abnormal or
staggering gait, increased time to tail flick, decreased landing foot
splay, decreased forelimb grip strength, decreased hindlimb grip
strength, decreased motor activity. There was no microscopic evidence
of neurotoxicity. There were no indications of neurotoxicity below a
lethal dose. The LEL was 300 mg/kg based on mortality, neurologic signs
described above and decreased body weight and food consumption. The
NOEL was 100 mg/kg.
Technical sulfosate (59.4% a.i.) was tested in a 90 day
neurotoxicity feeding study in Alpk: APfSD rats. Rats (12/sex/group)
received either 0, 200, 600, or 2,000 ppm (0, 15.6, 47.6 or 153.2 mg/
kg/day for males; 0, 18.2, 54.4 or 171.0 mg/kg/day for females) in the
diet. Six/sex/dose group received complete necropsy and
neurohistopathology. Positive control data were provided. The other 6/
sex/dose were perfused and the neurohistopathology carried out.
Clinical signs of toxicity, body weights, food consumption, functional
battery, motor activity and neuropathology parameters were measured and
recorded regularly. Positive control data were provided. At 2,000 ppm,
decreased body weights (16% for males and 9% for females), food
consumption and utilization were observed. In addition, mean forelimb
grip strength values for high dose females were statistically
significantly decreased over the values for the controls during weeks
5-14 (75 - 82% of controls). There was no microscopic evidence of
neurotoxicity. The significance of the decreased grip strength as a
neurotoxicological effect is less certain since there were no effects
in mean hindlimb grip strength for high dose females, in either of the
mean grip strength values at any time period for males, in any of the
other functional battery parameters, in motor activity values or in
neuropathology microscopic examinations for either sex. However, it
occurred at all time points, was statistically significant, and signs
of neurotoxicity occur in other studies. The LEL is 2,000 ppm (153.2
mg/kg/day) based on decreases in mean body weight, food consumption,
food utilization and mean forelimb grip strength values. The NOEL is
600 ppm (47.6 mg/kg/day).
Several mutagenicity tests were conducted. In some of the in vitro
mutagenicity tests (forward mutation/mouse lymphoma cells, structural
chromosomal aberrations/CHO cells), sulfosate induced a false positive
mutagenic effect. A common feature of
[[Page 48602]]
these tests was that the pHs of the test incubation media were acidic
(pH 5.67-7.07) due to the addition of sulfosate. These positive results
were no longer observed when the pH was readjusted to a more
physiological level (pH 7.4) before the mutagenicity tests were
conducted. Based on the available mutagenicity studies, there are no
concerns for mutagenicity at this time.
In a metabolism study, rats were treated with sulfosate soluble
concentrate (14C labeled). Radiolabelled trimethylsulfonium
ion (TMS) was rapidly excreted unmetabolized in urine and feces; the
principal sites of localization of TMS are adrenals, kidneys, bladder,
liver, thyroid and stomach.
In a metabolism study, rats were treated with sulfosate
(14C-labeled on the anionic part of the molecule, 56.1% ai).
Intravenous (IV) or oral 14C- sulfosate was rapidly
excreted; over a 5 day period most (86-95%) of the administered dose
was excreted in the urine & feces. IV treated male & females eliminated
90% of the administered dose in urine. Absorption of 14C-
sulfosate was incomplete by the oral route; most groups eliminated 47-
57% of the administered dose in the urine and 36-42% in the feces.
Females treated with a high dose eliminated less in the urine (36% of
dose) and more in the feces (54% of dose). There was negligible
14C-carbon dioxide (14CO2) elimination. Tissue
14C residues were < 0.32% of administered dose. Carcass
14C residues were < 2.2% of administered dose (mostly in
bones, 3-7 ppm in low dose rats & 19-32 ppm in high dose rats). Most
excreted radioactivity (77-96% of fecal; 80-95% of urinary) was
unchanged anion (carboxymethylamino-methylphosphonate). One fecal
metabolite (repeated dose females; 8.5% of fecal radioactivity) was
aminomethyl phosphonic acid. Several minor unidentified (:
3% of total urinary/fecal radioactivity) metabolites were recovered.
The low dose was 25 mg/kg. At the high dose of 250 mg/kg, toxic signs
were lethargy, moderate to severe depression, tremors, dehydration, and
decreased food consumption in 2 - 5 rats (total of 10 rats tested).
Recovery was within 72 hours.
B. Toxicological Endpoints
1. Acute toxicity. An acute NOEL of 100 mg/kg was determined based
on mortality, decreased body weight and food consumption, and
neurotoxicity at 300 mg/kg (LOEL) from an acute rat neurotoxicity
study. An acute RFD of 1.0 mg/kg was calculated by dividing the 100 mg/
kg NOEL by the uncertainty factor of 100 (10x for inter-species
extrapolation and 10x for intra-species variations). Based on FQPA, EPA
has determined that an additional safety factor of 3x must be retained
for the acute dietary assessment to protect infants and children.
Without the 3x safety factor, the level of concern is dietary
consumption above the level of 100% of the RfD. With the 3x safety
factor, the level of concern is consumption above the level of 33% of
the acute RfD.
2. Short - and intermediate - term toxicity. There are currently no
residential uses for suslfosate; therefore, assessment of short- and
intermediate-term toxicity is not necessary for the purpose of
establishing sulfosate tolerances.
3. Chronic toxicity. EPA has established the RfD for sulfosate at
0.10 milligrams/kilogram/day (mg/kg/day). This RfD is based on an oral
NOEL of 10 mg/kg/day (LOEL of 50 mg/kg/day) from a chronic oral gavage
study in dogs and an uncertainty factor of 100. Based on FQPA, EPA has
determined that an additional safety factor of 3x must be retained for
the chronic dietary assessment to protect infants and children. Without
the 3x safety factor, the level of concern is dietary consumption above
the level of 100% of the RfD. With the 3x safety factor, the level of
concern is consumption above the level of 33% of the chronic RfD.
4. Carcinogenicity. Sulfosate was classified as a ``Group E''
carcinogen (no evidence for carcinogenicity in humans) based on the
lack of evidence of carcinogenicity in mice and rats at doses that were
judged to be adequate to assess the carcinogenic potential and the
``Guidelines for Carcinogen Risk Assessment'' [51 FR 33992] for
classifying the weight-of-evidence for carcinogenicity.
C. Exposures and Risks
1. From food and feed uses. Tolerances have been previously
established (40 CFR 180.489) for the residues of sulfosate, in or on a
variety of raw agricultural commodities. Time-limited tolerances for
soybeans expired on April 10, 1998, and time limited tolerances for
corn, ruminants, poultry, milk, and eggs expired on March 9, 1998. Risk
assessments were conducted by EPA to assess dietary exposures and risks
from sulfosate as follows:
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 (food only) risk
assessment was conducted for sulfosate. The exposure to the most
sensitive population subgroup, in this instance non-nursing infants,
was 9.7% of the acute RfD (1.0 mg/kg bwt/day). Based on FQPA, EPA has
determined that an additional safety factor of 3x must be retained for
the acute dietary assessment to protect infants and children. Without
the 3x safety factor, the level of concern is dietary consumption above
the level of 100% of the RfD. With the 3x safety factor, the level of
concern is consumption above the level of 33% of the acute RfD.
Therefore, the acute dietary risk due to food does not exceed the level
of concern.
ii. Chronic exposure and risk. An chronic dietary (food only) risk
assessment was conducted for sulfosate. This risk assessment assumed
100% of the crops with existing tolerances plus those established in
this notice were treated and that residues were consumed at the
theoretical Maximum Residue Contribution (TMRC, the level of residues
consumed daily if each food item contained pesticide residues equal to
the tolerance). The exposure to the most sensitive population subgroup,
in this instance children 1 to 6 years old, was 20.3% of the chronic
RfD (0.1 mg/kg bwt/day). Based on FQPA, EPA has determined that an
additional safety factor of 3x must be retained for the acute dietary
assessment to protect infants and children. Without the 3x safety
factor, the level of concern is dietary consumption above the level of
100% of the RfD. With the 3x safety factor, the level of concern is
consumption above the level of 33% of the acute RfD. Therefore, the
chronic dietary risk due to food does not exceed the level of concern.
2. From drinking water. Results from computer modeling indicate
that sulfosate in groundwater will not contribute significant residues
in drinking water as a result of sulfosate use at the recommended
maximum annual application rate (1 application at 4.75 lbs., a.i.,
acre-1). The computer model uses conservative numbers,
therefore it is unlikely that groundwater concentrations would exceed
the estimated concentration of 0.00224 ppb, and sulfosate should not
pose a threat to ground water.
The surface water estimates are based on an exposure modeling
procedure called GENEEC (Generic Expected Environmental Concentration).
The assumptions of 1 application of 4.75 lbs., a.i., acre-1
resulted in calculated estimated maximum concentrations of 125 ppb
(acute, based on the highest 56 day value) and 35 ppb (chronic,
average). GENEEC modeling procedures assumed that sulfosate was applied
to a
[[Page 48603]]
10-hectare field that drained into a 1-hectare pond, 2-meters deep with
no outlet for all crops.
As a conservative assumption, because sulfosate residues in ground
water are expected to be insignificant compared to surface water, EPA
assumed that 100% of drinking water consumed was derived from surface
water in all drinking water exposure and risk calculations.
To calculate the maximum acceptable acute and chronic exposures to
sulfosate in drinking water, the dietary food exposure (acute or
chronic) was subtracted from 33% of the appropriate (acute or chronic)
RfD. DWLOCs were then calculated using the maximum acceptable acute or
chronic exposure, default body weights (70 kg - adult, 10 kg - child)
and drinking water consumption figures (2 litres - adult, 1 litre -
child).
i. Acute exposure and risk. OPP has calculated drinking water
levels of concern (DWLOCs) for acute exposure to be 9,740 ug/l parts
per billion (ppb) for U.S. population, 2,360 ug/l (ppb) for non-nursing
infants (<1 year old), and 2600 ug/l (ppb) for children (1-6 years
old). These levels include the FQPA additional safety factor of 3x to
protect infants and childern. The estimated maximum concentration of
sulfosate in surface water of 125 ppb (highest 56 day value) is less
than all of the calculated acute DWLOCs. Therefore, taking into account
the present uses plus uses on corn and soybeans, EPA concludes with
reasonable certainty that acute exposure to residues of sulfosate 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.
ii. Chronic exposure and risk. OPP has calculated DWLOCs for
chronic (non-cancer) exposure to be 925 ug/l (ppb) for U.S. population
and 130 ug/l (ppb) for the most sensitve population group, in this
instance children 1 to 6 years old. These levels include the FQPA
additional safety factor of 3x to protect infants and childern. The
estimated concentration 35 ppb (chronic, average) of sulfosate in
surface water of is less than all of the calculated chronic DWLOCs.
Therefore, taking into account the present uses plus uses on corn and
soybeans, EPA concludes with reasonable certainty that chronic exposure
to residues of sulfosate 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. Sulfosate is currently not registered
for use on any residential non-food sites: Therefore, residential
exposure to sulfosate residues will be through dietary exposure only.
4. Cumulative exposure to substances with common mechanism of
toxicity. Sulfosate is structurally similar to glyphosate. Further,
other pesticides may have common toxicity endpoints with sulfosate.
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 the
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 mechanism
issues can be resolved. These pesticides include pesticides that are
toxicologically dissimilar to existing chemical substances (in which
case 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 sulfosate 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,
sulfosate 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 sulfosate has a common mechanism of toxicity
with other substances.
D. Aggregate Risks and Determination of Safety for U.S. Population
1. Acute risk. Since there are no residential uses for sulfosate,
the acute aggregate exposure only includes food and water. For the U.S.
population, 5.8% of the acute RfD is occupied by dietary (food)
exposure. The estimated average concentrations of sulfosate in surface
and ground water are less than EPA's levels of concern for sulfosate in
drinking water as a contribution to acute aggregate exposure. The above
calculations include the FQPA safety factor of 3x. Therefore, EPA
concludes with reasonable certainty that residues of sulfosate in
drinking water do not contribute significantly to the aggregate acute
human health risk at the present time considering the present uses and
uses proposed in this action.
2. Chronic risk. Using the exposure assumptions TMRCs described
above, EPA has concluded that aggregate exposure to sulfosate from food
will utilize 7.6% of the RfD for the U.S. population. The major
identifiable subgroup with the highest aggregate exposure is children 1
to 6 years old (discussed below). 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. For infants, children, and
women, EPA determined that the 10x factor for increased susceptibility
of infants and children (as required by FQPA) should be reduced to 3x.
Therefore, for infants, children, and women, there is no concern for
exposures below 33% of the RfD. Despite the potential for exposure to
sulfosate in drinking water, EPA does not expect the aggregate exposure
to exceed 33% of the RfD.
3. Aggregate cancer risk for U.S. population. Sulfosate was
classified as a
[[Page 48604]]
``Group E'' carcinogen (no evidence for carcinogenicity in humans, see
section B.4 of this document).
4. Conclusions. EPA concludes that there is a reasonable certainty
that no harm will result from aggregate exposure to sulfosate 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 sulfosate, 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 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 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 a prenatal developmental
toxicity study, sulfosate was administered by gavage to groups of
pregnant Sprague-Dawley rats on gestation days 6-20 at dose levels of
0, 30, 100, or 333 mg/kg/day. The maternal NOEL was 100 mg/kg/day and
LOEL was 333 mg/kg/day based on decreased body weight, food
consumption, and increased clinical signs. The developmental NOEL was
100 mg/kg/day and LOEL was 333 mg/kg/day based on decreased fetal body
weight.
In another prenatal developmental toxicity study, Sulfosate was
administered by gavage to groups of New Zealand White rabbits on
gestation days 6-18 at doses of 0, 10, 40, or 100 mg/kg/day. The
maternal NOEL was 40 mg/kg/day and LOEL was 100 mg/kg/day based on
abortions, deaths, decreased body weight and food consumption. The
developmental NOEL was 40 mg/kg/day and LOEL was 100 mg/kg/day based on
decreased number (7) of surviving does, and decrease in number of live
fetuses/doe (5.4 vs 7.4 in controls).
iii. Reproductive toxicity study. Sulfosate was administered by
diet to Sprague-Dawley rats at dose levels of 0, 150, 800, or 2,000 ppm
for 2-generations. The parental systemic NOEL was 140 ppm (7.5 mg/kg/
day) and the LOEL was 800 ppm (40 mg/kg/day) based on decreased body
weight, decreased organ weights and decreased food consumption. The
reproductive/offspring NOEL was 7.5 mg/kg/day (140 ppm) and LOEL was 40
mg/kg/day (800 ppm) based on decreased pup body weight during
lactation.
iv. Pre- and post-natal sensitivity. The data provided no
indication of increased susceptibility in rats or rabbits from in utero
and/or post natal exposure to sulfosate. In the prenatal developmental
toxicity study in rats, evidence of developmental toxicity was seen
only in the presence of maternal toxicity. In the developmental
toxicity study in rabbits, developmental toxicity was seen in the
presence of maternal toxicity at the highest dose level. In the 2-
generation reproduction study in rats, effects in the offspring were
observed only at or above treatment levels which results in evidence of
parental toxicity. It should be noted that a developmental
neurotoxicity study is required.
v. Developmental neurotoxicity. A developmental neurotoxicity study
is not available. One is required due to neurotoxicity observed in the
rat, dog and mouse. Sulfosate is a neurotoxic chemical, which produces
clinical findings such as salivation, tremors, emesis, and decreased
activity in dogs and/or rats. Salivation was the most consistent sign,
and in dogs may have served as a precursor to more severe symptoms. In
one study, salivation stopped upon withdrawal of sulfosate and recurred
upon reintroduction of treatment. Dogs appear to be the most sensitive
species for these effects, with high intra-individual variability in
sensitivity. Acute neurotoxicity effects observed after a single dose
of 300 mg/kg in the rat included ptosis, decreased activity, decreased
splay reflex, upward curvature of spine, shaking, sides pinched in,
signs of urinary incontinence, irregular breathing, hunched posture,
abnormal or staggering gait, increased time to tail flick, decreased
landing foot splay, decreased forelimb grip strength, decreased
hindlimb grip strength, decreased motor activity. There was also death
at this dose. In the subchronic rat neurotoxicity study, the decreased
forelimb grip strength observed at 153 mg/kg/day, in females only, may
also have been due to treatment. Hydrocephalus or dilated ventricles
were observed in at least one animal at the HDT (50 mg/kg/day) in adult
dogs in all the dog studies, following both 90-days (gavage or capsule)
and one year of dosing. This finding was never seen in controls or low
dose groups. Hydrocephaly and/or dilated ventricles in dogs of this age
may have been due to inherent asymptomatic incidences in the beagle
(Vullo et al., 1997), but it was noted that these animals were not
supplied by the same breeding colony, and the incidences were only
observed at the high dose levels across several studies. Therefore,
these findings can not be dismissed. Neuropathology was observed in the
21-day rat dermal study (sciatic nerve degeneration) at 1000 mg/kg, and
the 2-year chronic mouse study (degeneration of the sciatic nerve,
lumbar spinal root, and lumbar spinal white matter in males) at 991 mg/
kg. Although these findings were previously discounted due to lack of
supporting neuropathology data in the acute and subchronic
neurotoxicity studies in rats, the overall neurotoxicity profile of the
chemical indicated that the neuropathology could be a treatment-related
effect of concern.
v. Conclusion. EPA concludes that the 10x factor for increased
susceptibility of infants and children (as required by FQPA) should be
reduced to 3x. The Agency determined that the data indicate that there
is no increased susceptibility to young rats or rabbits following in
utero exposure in prenatal studies or in the postnatal study in rats,
and the guideline requirements for the toxicology data base are
completed. Additionally, the exposure assessments for sulfosate do not
indicate a concern for potential risk to infants and children since:
(1) The dietary exposure assessments are unrefined (assuming that all
commodities contain tolerance level residues) resulting in an over
estimate of dietary exposure; (2) data from modeling are used for the
ground and surface source drinking water exposure assessments,
resulting in estimates considered to be reasonable upper-bound
concentrations; and (3) there are currently no registered residential
uses for sulfosate.
[[Page 48605]]
However, the FQPA safety factor was reduced to 3x instead of being
removed because of the concern for the overall neurotoxicity exhibited
in long-term studies in adult animals (mice, rats, and dogs) and the
Agency's determination based on these findings that additional data are
needed. In mice, sulfosate induced degeneration of the sciatic nerve,
lumbar spinal root and lumbar spinal white matter was reported. In
rats, degeneration of the sciatic nerve was seen following dermal
applications. In dogs, hydrocephalus and/or dilated ventricles were
observed following subchronic and chronic exposures. In addition,
clinical signs indicative of neurotoxicity such as salivation, tremors,
emesis, decreased activity was seen in rats and dogs. Based on these
factors, the Agency determined that a developmental neurotoxicity study
in rats is required to characterize the observed neuropathology in the
subchronic and chronic studies.
2. Acute risk. Since there are no residential uses for sulfosate,
the acute aggregate exposure only includes food and water. For infants
and children, 7.3-9.4% of the acute RfD is occupied by dietary (food)
exposure. The estimated average concentrations of sulfosate in surface
and ground water are less than EPA's levels of concern for sulfosate in
drinking water as a contribution to acute aggregate dietary exposure.
The above calculations include the FQPA safety factor of 3x. Therefore,
EPA concludes with reasonable certainty that residues of sulfosate in
drinking water do not contribute significantly to the aggregate acute
human health risk at the present time considering the present uses and
uses proposed in this action. EPA concludes that there is a reasonable
certainty that no harm will result to infants and children from
aggregate acute exposure to sulfosate residues.
3. Chronic risk. Using the conservative exposure assumptions
described above, EPA has concluded that aggregate exposure to sulfosate
from food will utilize 11.9-20.3% of the RfD for infants and children.
EPA has no concern for exposures below 33% 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 health of infants
and children. Despite the potential for exposure to sulfosate in
drinking water, EPA does not expect the aggregate dietary exposure to
exceed 33% of the RfD. EPA concludes that there is a reasonable
certainty that no harm will result to infants and children from
aggregate exposure to sulfosate residues.
III. Other Considerations
A. Metabolism In Plants and Animals
The nature of the residues in plants and animals is understood.
EPA has determined that the tolerance expression for sulfosate must
include both of the parent ions.
B. Analytical Enforcement Methodology
1. Plants. Analytical methods are available for enforcement. There
is currently a PAM II enforcement method for the N-
(phosphonomethyl)glycine anion (PMG) in crops. For TMS, the registrant
has proposed gas chromatography (GC) Method RR 93-105B as the
analytical enforcement method. A successful petition method validation
(PMV) of this analytical enforcement method for the TMS moiety in
plants has been completed by the EPA laboratory. EPA concludes that
Method RR 93-105B is adequate for enforcement of the permanent
tolerances.
2. Animals. Analytical methods are available for enforcement. For
PMG, the registrant has proposed GC Method RR 93-104B as the analytical
enforcement method. For TMS, the registrant has proposed GC Method RR
93-100B as the analytical enforcement method. Successful PMV of these
analytical enforcement methods for the PMG and TMS moieties in meat,
milk and eggs have been completed by the EPA laboratory. EPA concludes
that Method RR 93-104B and Method RR 93-100B are adequate for
enforcement of the permanent tolerances.
C. Magnitude of Residues
The crop field trial data are adequate to support these tolerances.
D. International Residue Limits
There are no Codex, Canadian or Mexican tolerances or maximum
residue limits for residues of sulfosate in the subject crops.
Therefore, a compatibility issue is not relevant to the proposed
tolerances.
E. Rotational Crop Restrictions.
EPA has previously reviewed two confined rotational crop studies
for sulfosate and concluded that rotational crop restrictions were not
required .
IV. Conclusion
Therefore, the tolerance is established for residues of sulfosate
in cattle, goats, horses, hogs and sheep at 0.10 ppm in fat, at 1.00
ppm in meat by-products, and at 0.20 ppm in meat; in poultry at 0.05
ppm in fat, meat-by-products (except liver), and meat, and at 0.10 ppm
in liver; in eggs at 0.02 ppm; in milk at 0.20 ppm; in corn at 0.30 ppm
(of which no more than 0.20 ppm is TMS) in stover (field and pop), at
0.20 ppm (of which no more than 0.10 ppm is TMS) in grain (field and
pop), at 0.10 ppm in forage (field); in soybeans at 2.00 ppm (of which
no more than 1.0 ppm is TMS) in forage, at 5.00 ppm (of which no more
than 2.0 ppm is TMS) in hay, and at 3.00 (of which no more than 1.0 ppm
is TMS) ppm in seed; and in aspirated grain fractions at 210 ppm (of
which no more than 60 ppm is TMS). In addition, the existing tolerances
for prunes at 0.20 ppm, raisins at 0.20 ppm, and soybean hulls at 7.0
ppm are moved from 40 CFR 185.5375 to 40 CFR 180.489.
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 November 10, 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 prescribed by 40
CFR 180.33(i). 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
[[Page 48606]]
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-300709 (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 Highway, Arlington, VA.
Electronic comments may be sent directly to EPA at:
[email protected].
Electronic comments must be submitted as an ASCII file avoiding the
use of special characters and any form of encryption.
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 Other 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).
B. Executive Order 12875
Under Executive Order 12875, entitled Enhancing Intergovernmental
Partnerships (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 the Office of Management and Budget (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 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 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.
In addition, since tolerances and exemptions that are established
on the basis of a petition under FFDCA section 408(d), such as the
tolerances 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.
[[Page 48607]]
VIII. Submission to Congress and the General Accounting Office
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 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 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,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.
40 CFR Part 185
Environmental protection, Food additives, Pesticides and pests.
Dated: August 31, 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. Section 180.489 is revised to read as follows:
Sec. 180.489 Sulfosate (Sulfonium, trimethyl-salt with N-
(phosphonomethyl)glycine (1:1)); tolerances for residues.
(a) General . Tolerances are established for residues of the
herbicide sulfosate (sulfonium, trimethyl-salt with N-
(phosphonomethyl)glycine (1:1)) in or on the following raw and
processed agricultural commodities:
------------------------------------------------------------------------
Commodity Parts per million
------------------------------------------------------------------------
Almond, hulls (of which no more than 0.30 1.00
ppm is trimethylsulfonium (TMS)).
Aspirated grain fractions (of which no 210.00
more than 60 ppm is TMS).
Bananas (imported only)a.................. 0.05
Cattle, fat............................... 0.10
Cattle, mbyp.............................. 1.00
Cattle, meat.............................. 0.20
Citrus fruit group........................ 0.05
Corn, field, forage....................... 0.10
Corn, field and pop, grain (of which no 0.20
more than 0.10 ppm is TMS).
Corn, field and pop, stover (of which no 0.30
more than 0.20 ppm is TMS).
Eggs...................................... 0.02
Goats, fat................................ 0.10
Goats, mbyp............................... 1.00
Goats, meat............................... 0.20
Grape..................................... 0.10
Hogs, fat................................. 0.10
Hogs, mbyp................................ 1.00
Hogs, meat................................ 0.20
Horses, fat............................... 0.10
Horses, mbyp.............................. 1.00
Horses, meat.............................. 0.20
Milk...................................... 0.20
Poultry, fat.............................. 0.05
Poultry, liver............................ 0.05
Poultry, mbyp (except liver).............. 0.10
Poultry, meat............................. 0.05
Prune (of which no more than 0.05 ppm is 0.20
TMS).
Raisin (of which no more than 0.05 ppm is 0.20
TMS).
Sheep, fat................................ 0.10
Sheep, mbyp............................... 1.0
Sheep, meat............................... 0.20
Soybean, forage (of which no more than 1 2.0
ppm is TMS).
Soybean, hay (of which no more than 2 ppm 5.0
is TMS).
Soybean, hulls (of which no more than 2 7.0
ppm is TMS).
Soybean, seed (of which no more than 1 ppm 3.0
is TMS).
Stone fruit group......................... 0.05
Tree nut group............................ 0.05
------------------------------------------------------------------------
aThere are no U.S. registrations as of the date of publication of the
tolerance in the Federal Register.
(b) Section 18 emergency exemptions. [Reserved]
(c) Tolerances with regional registrations. [Reserved]
(d) Indirect or inadvertent residues. [Reserved]
PART 185 -- [AMENDED]
1. The authority citation for part 185 continues to read as
follows:
Authority: 21 U.S.C. 346a and 348.
Sec. 185.5375 [Removed]
2. By removing Sec. 185.5375 Sulfonium, trimethyl-salt with N-
(phosphonomethyl)glycine (1:1).
[FR Doc. 98-24468 Filed 9-10-98; 8:45 am]
BILLING CODE 6560-50-F