Document ID: EPA-HQ-OPP-2006-0323-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2007-02-07T05:00Z

FILE NAME:   62719.wpt   (12/29/2005) (xml)

Template Number P25	

ATTENTION: 

All commodity terms must comply with the Food and Feed Commodity
Vocabulary database (http://www.epa.gov/pesticides/foodfeed/).

All text in blue font (instructions for preparing the document), should
be removed prior to sending the document to the Federal Register Staff. 
Instructional text and prompts in green font should also be removed.

COMPANY FEDERAL REGISTER DOCUMENT SUBMISSION TEMPLATE

(1/1/2005)

EPA Registration Division contact: [James A. Tompkins 703-305-5697]	

TEMPLATE:

[Glyphosate dimethylammonium salt or dimethylamine (DMA) salt of
–(phosphonomethyl)glycine]  to the existing list of tolerances
established  for residues of glyphosate (n-phosphomethyl)glycine)
resulting from the application of glyphosate, the isopropylamine salt of
glyphosate, the ethanolamine salt of glyphosate, the ammonium salt of
glyphosate and the potassium of glyphosate in or on the currently EPA
approved  raw agricultural commodities as listed in 40 CFR part 180.364.
 EPA has determined that the petition contains data or information
regarding the elements set forth in section 408(d)(2) of the FFDCA;
however, EPA has not fully evaluated the sufficiency of the submitted
data at this time or whether the data supports granting of the petition.
 Additional data may be needed before EPA rules on the petition.

                                      

. [Adequate enforcement methods are  available for analysis of residues
of glyphosate in or on plant commodities.  These methods include gas
liquid chromathography (GLC) (Method I in Pesticides Analytical Manual
(PAM) II; the limit of detection is 0.05 ppm) and High Performance
Liquid Chromatography (HPLC) with fluorometric detection. The HPLC
procedure has undergone successful Agency validation, and was
recommended for inclusion in PAM II. A gas chromatography/mass
spectrometry (GC/MS) method for glyphosate crops has also been validated
by EPA’s Analytical Chemistry Laboratory (ACL).  The proposed revision
in the tolerance regulation does not change the residue to be analyzed,
which remains as glyphosate per se.]

	

. [Adequate data concerning glyphosate residues on RACs has previously
been submitted to the Agency.  Accordingly, the available residue data
for glyphosate support the proposed revision of the tolerance expression
for glyphosate.  As noted above, the proposed revision will permit
glyphosate residues from the application of glyphosate in the form of
its dimethylammonium salt.   In addition, any secondary residues
occurring in liver or kidney of cattle, goats, horses  and sheep, 
meat-by-products of poultry and eggs, will be covered by existing
tolerances.  Any residues occurring in harvestable aquatic species will
be covered by existing glyphosate tolerances for fish and shellfish.]

.  [EPA has previously 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 table below compares the acute toxicity results of glyphosate
(–phosphonomethyl glycine) against toxicity results of glyphosate DMA
salt as in GF-1667, demonstrating the lower toxicity of the glyphosate
DMA salt.



	

	Glyphosate	

GF-1667 Glyphosate DMA Salt

Test	

Result	

Category	

Result	

Category

Acute Oral (Rat)	

Technical: > 4320 mg/kg	

III	

> 5000 mg/kg	

IV

Acute Dermal (rabbit)	

Technical: > 2 g/kg	

III	

(Rats) > 5000 mg/kg	

IV

Acute Inhalation	

Technical: Not required	

N/A	

(4 hr) LC50 > 5.21 mg/L	

IV

Eye Irritation	

MP: mid irritation, clear in 7 days	

III	

slight iritis and conjunctival irritation, cleared < 72 hr	

III

Dermal Irritation	

MP: Slight irritation	

IV	

Irritation cleared < 48 hr	

III

Skin Sensitization	

MP: negative	

N/A	

Negative	

N/A

MP: Manufacturing Products .]

.  [In vitro rec-assay with B. Subtilis H17 (rec+) and M45 (rec-) and
reverse mutation assay using E. Coli WP2 hcr and S. Typhimurium strains:
 There was no evidence of genotoxicity up to the limit dose or
cytotoxicity in the presence or absence of metabolic activation.

In vitro reverse gene mutation assay in S. Typhimurium bacteria:  There
was no evidence of induced mutant colonies over background in Salmonella
strains TA 98, TA 100, TA 1535, and TA 1537 both in the presence and
absence of metabolic activation, at doses up to cytoxic levels or the
limit dose.

In vitro gene mutation assay in Chinese hamster ovary cells/HGPRT: 
There was no evidence of genotoxicity up to cytotoxic levels in the
presence or absence of metabolic activation. 

Bone marrow chromosome aberrations assay:   There was no significant
increase in the frequency of chromosome aberrations in bone marrow at
the limit dose of 1,000 mg/kg in both sexes of Sprague-Dawley rats.]



.  [i.  Prenatal developmental toxicity in rats: 

Maternal NOAEL = 1,000 mg/kg/day day based on mortality, LOAEL = 3,000
mg/kg/day based on mortality, increased clinical signs, and reduced body
weight gain. Developmental NOAEL = 1,000 mg/kg/day based on decreases in
total implantations/dam and nonviable fetuses /dam, increased number of
litters and fetuses with unossified sternebrae, and decreased fetal body
weight.

ii.  Prenatal developmental toxicity in rabbits:  Maternal NOAEL = 175
mg/kg/day, LOAEL = 350 mg/kg/day based on mortality, and clinical signs.
 Developmental NOAEL = 175 mg/kg/day, LOAEL = 350 mg/kg/day
(insufficient litters available to assess developmental toxicity).

[i.  90-Day oral study toxicity in rats:  NOAEL less than 50 milligrams
(mg) / kilogram (kg) / day for both sexes.  LOAEL = 50 mg/kg/day based
on increased phosphorus and potassium in both sexes

ii.  90-Day oral toxicity in mice:  NOAEL = 1,500 mg/kg/day in both
sexes LOAEL = 7,500 mg/kg/day in both sexes based on decreased body
weight gain in both sexes.

iii.  28-day dermal study 21/28-Day dermal toxicity in rabbits:  NOAEL =
1,000 mg/kg/day for males and 5,000 mg/kg/day for females.  LOAEL =
5,000 mg/kg/day in males based on decreased food consumption .]

. [i. Chronic toxicity in dogs: NOAEL= 500 mg/kg/day highest does
tested).   LOAEL greater than 500 mg/kg/day.

ii.  Combined Chronic Toxicity/Carinogenicity in rats:  NOAEL = 362
mg/kg/day in males and 457 mg/kg/day in females.  LOAEL = 940 mg/kg/day
in males and 1,183 mg/kg/day in females based on decreased weight gain
in 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.  There was no evidence of
carcinogenicity.  

. [Metabolism in rats:  Following a single oral dose, 30-36% was
absorbed and less than 0,27% was eliminated as CO2.  Urine and feces
contained 97.5% as parent. Aminomethylphosphonic acid (AMPA) was only
metabolite found at 0.2-0.3% of administered dose. Less than 1.0% of the
absorbed dose remained in tissues and organs, primarily in the bone.]

.  [The EPA does not consider AMPA a metabolite of concern, and is not
included in the risk assessment.  AMPA is slightly hazardous to rats
given a single oral dose, with an LD50 of 8300 mg/kg of body weight
(WHO, 1996).  In a 90-day study of toxicity in rats receiving AMPA, the
NOAEL was 400 mg/kg of body weight per day.  In a 90-day study of
toxicity in dogs receiving AMPA, the NOAEL was 300 mg/kg of body weight
per day.  No indication of genotoxic activity was seen in studies of
gene mutation in bacteria, of DNA repair in bacteria and mammalian cells
in vitro or of micronucleus formation in vivo.  No assays for gene
mutation were performed in mammalian cells in vitro, but the structural
similarity of AMPA to glyphosate and the lack of genotoxicity of
glyphosate, including in an assay for gene mutation in mammalian cells
in vitro, indicate that such an assay with AMPA would be redundant.

The NOAEL for developmental toxicity was 400 mg/kg of body weight per
day.  AMPA did not induce dermal or ocular irritation in rabbits.  No
long-term study of the toxicity or carcinogenicity of AMPA has been
carried out, but in the more recent of two such studies with
technical-grade glyphosate in rats at dietary levels of 0.2, 0.8 or 2%,
the AMPA content of the test compound was given, namely 0.68%. The NOAEL
for technical-grade glyphosate was 0.8% in the diet, corresponding to
400 mg/kg of body weight per day for glyphosate and 2.7 mg/kg of body
weight per day for AMPA.  No increase in tumour incidence was seen in
this study.  No multigeneration study of the reproductive toxicity of
AMPA has been reported, but in a recent two-generation study in rats
with technical-grade glyphosate at dietary levels of 0.2, 1 or 3%, the
test compound contained 0.61% AMPA. The NOAEL was 1% in the diet,
corresponding to 740 mg of glyphosate per kg of body weight per day, and
4.5 mg of AMPA per kg of body weight per day.

1 This section was taken and edited from FAO/WHO (1998).]

.  [The above studies  measure numerous endpoints with sufficient
sensitivity to detect potential endocrine-modulating activity.  No
effects have been identified in subchronic, chronic or developmental
toxicity or multi-generation reproduction studies to indicate any
endocrine-modulating activity by glyphosate.  In addition, adverse
effects were not  seen when glyphosate was tested in a dominant-lethal
mutation assay.  While this assay was designed as a genetic toxicity
test, agents that can affect male reproduction function will also cause
effects in this assay.]



.  [Food and feed uses:  Tolerances have been established (40CFR
180.364) for the residues in (N-phosphonomethyl) glycine resulting from
the application of the isopropylamine salt of glyphosate, the ammonium
salt of glyphosate and/or the ethanolamine salt of glyphosate  in or on
a variety of food commodities.  The petitioner proposes to add the
glyphosate dimethylammonium salt to this list of acceptable salt forms
to which the tolerances apply. This amendment will not change the
dietary exposure assessment because the magnitude of the tolerances are
unchanged, and present dietary exposure estimates have already included
the worst-case assumption of tolerance level residues and that 100% of
the crop has been treated.]

	

.  [Risk assessments were conducted by EPA to assess dietary exposure
from glyphosate in food as follows:  

a.  Acute dietary exposure: Acute dietary risk assessments are performed
for the food-use pesticide if a toxicological study has indicated that
the possibility of an effect of concern occurring as a result of a 1 day
or single exposure. An acute dietary endpoint and dose were not
identified for glyphosate.  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 are no data requirements for
acute and subchronic rat neurotoxicity studies, since there was no
evidence of neurotoxicity in any of the toxicology studies at very high
doses and glyphosate lacks a leaving group.

b.  Chronic dietary exposure.  In conducting this chronic dietary risk
assessment, the Dietary Exposure Evaluation Model (DEEM) analysis
evaluated the individual food consumption, as reported by respondents in
the USDA 1989-1992 nationwide Continuing Surveys of Food Intake by
Individuals (CSFII) and accumulated exposure to the chemical for each
commodity. The following assumptions were made for the chronic exposure
assessments:  The chronic dietary exposure analysis 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 from a developmental study and an
uncertainty factor of 100 (applicable to all population subgroups). The
DEEM analysis assumed tolerance level residues and 100% of the crop
treated in/on all commodities with an existing or proposed glyphosate
tolerance. These assumptions resulted in the following theoretical
maximum residue contributions (TMRC) and percentage RfDs for certain
population subgroups. The TMRC for the U.S. population (48 contiguous
States) was 0.033727 mg/kg/day or 1.7% of the RfD, 0.029752 mg/kg/day or
1.5% of the RfD for nursing infants (less than 1 year old);  0.094859
mg/kg/day or 4.7% of the RfD for non-nursing infants (less than 1 year
old);  0.072062 mg/kg/day or 3/6% of the RfD of children (1-6 years
old);  0.047815 mg/kg/day or 2.4% of the RfD for children (7-12 years
old);  0.034216 mg/kg/day or 1.7% of the RfD for females (13+/nursing); 
0.033234 mg/kg/day or 1.6% of the RfD for non-Hispanic whites; and
0.035141 mg/kg/day or 1.7% of the RfD for non-Hispanic blacks.

.   The available field and laboratory data indicate that glyphosate
absorbs strongly to soil and would not be expected to move vertically
below the 6 inch soil layer.  Based on non-aged batch equilibrium
studies, glyphosate and glyphosate residues are expected to be immobile
with Kd (ads) values ranging from 62 to 175. The mechanism of absorption
is unclear; however, it is speculated that it may be associated with
vacant phosphate sorption sites or high levels of metallic soil cations.
 The data indicate that chemical and photochemical decomposition is not
a significant pathway of degradation of glyphosate in soil and water.
However, glyphosate is readily degraded by soil microbes to AMPA, which
is degraded to CO2, although at a slower rate than parent glyphosate.
Because the glyphosate anion and the potassium cation will be completely
dissociated in environmental media, the proposed use of potassium
glyphosate solutions will not change the environmental properties of
glyphosate.

The Agency lacks sufficient monitoring exposure data to complete a
comprehensive dietary exposure analysis and risk assessment for
glyphosate in drinking water. Because the Agency does not have
comprehensive monitoring data, drinking water concentration estimates
are made by reliance on simulation or modeling taking into account data
on the physical characteristics of glyphosate.

The Agency uses the Generic Expected Environmental Concentration
(GENEEC) or the Pesticide Rood Zone/Exposure Analysis Modeling System
(PRZM/EXAMS) to estimate pesticide concentrations in surface water, and
the Screening Concentration and Ground Water (SCI-GROW) model, which
predicts pesticide concentrations in ground water.  In general,  EPA
will use GENEEC (a tier 1 model) before using PRZM/EXAMS (a tier 2
model) for a screening-level assessment for surface water. The GENEEC
model is a subset of the PRZM/EXAMS model that uses a specific high-end
runoff scenario for pesticides. GENEEC incorporates a farm pond
scenario, while PRZM/EXAMS incorporate in index reservoir environment in
place of the previous pond scenario. The PRZM/EXAMS model includes a
percent crop area factor as an adjustment to account for the maximum
percent crop coverage with a watershed or drainage basin.

None of these models include consideration of the impact processing
(mixing, dilution or treatment) of raw water for distribution as
drinking water would likely have on the removal of pesticides from the
source water.  The primary use of these models by the Agency at this
stage is to provide a coarse screen for sorting out pesticides, for
which it is highly unlikely that drinking water concentrations would
ever exceed human health levels of concern.

Since the models used are considered to be screening tools in the risk
assessment process, the Agency does not use estimated environmental
concentrations (EEC) from these models to quantify drinking water
exposure and risk as a %RfD or %PAD.  Instead, drinking water levels of
comparison (DWLOCs) are calculated and used as a point of comparison
against the model estimates of a pesticide’s concentration in water.
DWLOCs are theoretical upper limits on a pesticide’s concentration in
drinking water in light of total aggregate exposure to a pesticide in
food, and from residential uses. Since DWLOCs address total aggregate
exposure to glyphosate they are further discussed in the aggregate risk
sections below. 

Using available environmental fate parameters and assuming two
applications with a

re-treatment interval of 90 days at a rate of 5 lbs. ai/A (3.75 lbs
ae/A), the ground water EEC from glyphosate using SCO-GROW was 0.0038
parts per billion (ppb). The current label allows multiple applications
of 0.37 - 5 lbs ai/A up to a maximum of 10.6 lbs ai/A/year. The ground
water EECs generated by SCI-GROW are based on the largest 90-day average
recorded during the sampling period. Since there is relatively little
temporal variation in ground water concentrations compared to surface
water, the concentrations can be considered as acute and chronic values.

The GENEEC model was used to estimate surface water concentrations for
glyphosate resulting from its maximum use rate on crops. GENEEC is a
single event model (one runoff event), but can account for spray drift
from multiple applications. GENEEC represents a 10 hectare field
immediately adjacent to a 1 hectare pond that is 2 meters deep with no
outlet. The pond receives a spray drift event from each application plus
one runoff event. The runoff event moves a maximum of 10% of the applied
pesticide into the pond. This amount can be reduced due to degradation
on the field and by soil sorption.  Spray drift is estimated as 5% of
the application rate. The GENEEC values represent upper-bound estimates
of the concentrations that might be found in the surface water due to
the glyphosate use. Thus, the GENEEC model predicts that glyphosate
surface water EECs range from a peak of 21 ppb to a 56-day average of
2.5 ppb.  For comparison purposes, EPA guidance suggests dividing the
56-day GENEEC EED value by 3 before comparison to the calculated
DWLOCchronic value (“Interim Guidance for Incorporating Drinking Water
Exposure into Aggregate Risk Assessments, 01-Aug-199, SOP 99.5).  Thus,
2.5 divided by 3 or 0.83 ppb is the predicted surface water EEC value
resulting from glyphosate treatment of crops.

To  estimate the possible concentration of glyphosate in surface water
resulting from direct application to water, EPA assumed application to a
water body 6 feet deep.  At an application rate of 3.75 lbs ae/A, the
estimated peak concentration is 230 ppb.  Using this peak value in a
first-order dissipation model with a half-life for glyphosate in water
of 7.5 days, the resulting 56-day average value divided by 3, or 15.4
ppb, is the predicted surface water EEC resulting from direct
application to water.  Because the glyphosate water-application estimate
is greater than the crop-application estimate, 15/4 ppb is the
appropriate chronic value to compare to the calculated DWLOCchronic 
value for aggregate risk considerations.

Based on the GENEEC and SCI-GROW models the EECs of glyphosate for
chronic exposures are estimated to be 15.4 ppb for surface water and
0.004 ppb for ground water.]

. [Residential uses:  The term “residential exposure” is used in
this document to refer to non-occupational, non-dietary exposure (e.g.;
for lawn and garden pest control, indoor pest control, termiticides, and
flee and tick control on pets).

Glyphosate is currently registered for use on the following residential
non-dietary sites:  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 low acute toxicity and the lack of other toxicological concerns,
exposures from residential uses of glyphosate are not expected to pose
undue risks.]

[Cumulative exposure to substances with a 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, at this time, have 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
purpose 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 (62 FR 62961, November 26, 1997).]

.  [To estimate total aggregate exposure to a pesticide from food,
drinking water,and residential uses, the Agency calculates DWLOCs which
are used as a point of comparison against the model estimates of a
pesticide’s concentration in water (EECs).  DWLOC values are not
regulatory standards for drinking water.  DWLOCs are theoretical upper
limits on a pesticide’s concentration in drinking water in light of
total aggregate exposure to a pesticide in food and residential uses. 
In calculating a DWLOC, the Agency determines how much of the acceptable
exposure (i.e., the PAD) is available for exposure through drinking
water; e.g., allowable chronic water exposure (mg/kg/day) = cPAD -
(average food + residential exposure).  This allowable exposure through
drinking water is used to calculate a DWLOC.

A DWLOC will vary depending on the toxic endpoint, drinking water
consumption and body weights. Default body weights and consumption
values as used by the USEPA Office of Water are used to calculate
DWLOCs:  2L/70 kg (adult male), 2L/60 kg (adult female), and

1L/10 kg (child).  Default body weights and drinking water consumption
values vary on an individual basis.  This variation will be taken into
account in more refined screening-level and quantitative drinking water
exposure assessments.  Different populations will have different DWLOCs.
 Generally, a DWLOC is calculated for each type of risk assessment used:
acute, short-term, intermediate-term, chronic and cancer.

When EECs for surface water and ground water are less than the
calculated DWLOCs, OPP concludes with reasonable certainty that
exposures to the pesticide in drinking water (when considered along with
other sources of exposure for which OPP has reliable data) would not
result in unacceptable levels of aggregate human health risk at this
time.  Because OPP considers the aggregate risk resulting from multiple
exposure pathways associated with a pesticide’s uses, levels of
comparison in drinking water may vary as those uses change. If new uses
are added in the future, OPP will reassess the potential impacts of
residues of the pesticide in drinking water as a part of the aggregate
risk assessment process.

a. Acute risk.  No appropriate toxicological endpoint for a single dose
exposure was identified in oral toxicity studies with glyphosate.
Therefore, an acute RfD was not established, and there is no expectation
of acute dietary risk from food and water.

b. Chronic Risk. Using the exposure assumptions described in this unit
for chronic exposure, EPA has concluded that exposure to glyphosate from
food using present tolerances and all proposed new tolerances will
utilize 1.7% of the cPAD for the U.S. population, 3.8% of the cPAD for
all infants less than 1 year old and 3.6% of the cPAD for children (1 to
6 years old).  These dietary exposure levels are unaffected by the
proposed tolerance regulation change.  Based on the use pattern, chronic
residential exposure to residues of glyphosate is not expected.  In
addition, there is potential for chronic dietary exposure to glyphosate
in drinking water.  After calculating DWLOCs and comparing them to the
EECs for surface and ground water, EPA does not expect the aggregate
exposure to exceed 100% of the cPAD, as shown in the following 

Table.

Aggregate Risk Assessment for Chronic (Non-Cancer) Exposure to
Glyphosate

Population	

Subgroup	cPAD

mg/kg/day	%cPAD

(Food	Surface

Water EEC

(ppb)	Ground 

Water EEC

(ppb)	DWLC

(ppb)

U.S.

Population		2.0	1.7	15.4	0.004	69,000

Non-nursing Infants, less Than 1 year Old	2.0	4.7	15.4	0.004	19,000

All infants, less than 1 Year old	2.0	3.8	15.4	0.004	19,000

Children, 1-6 Years old	2.0	3.6	15.4	0.004	19,000

------------------------------------------------------------------------
---------------------------------------------	c. Short- and
intermediate-term risk.  Short- and intermediate-term aggregate exposure
takes into account residential exposure plus chronic exposure to food
and water (considered to be a background exposure level).  Though
residential exposure could occur with the use of glyphosate, no
toxicological effects have been identified for short- or
intermediate-term toxicity.  Therefore, the aggregate risk is the sum of
the risk from food and water, which do not exceed the Agency’s level
of concern.

d. 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.  Glyphosate is not expected
to pose a cancer risk to humans.

e. Determination of safety.  Based on these risk assessments, Monsanto
concludes that there is reasonable certainty that no harm will result
from the aggregate exposure to glyphosate residues.]

. [i. In general, FFCDA 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 prenatal and postnatal toxicity, and
the completeness of the database on toxicity and exposure 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
x 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 effects in
infants and 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. Prenatal and postnatal sensitivity: There is no evidence of
increased susceptibility in rats and rabbits to in utero and/or
postnatal exposure to glyphosate.

iii. Conclusion:  There is a complete toxicity data base for glyphosate,
and exposure data are complete or are estimated based on data that
reasonably accounts for potential exposures.  EPA determined that the
10X safety factor to protect infants and children should be removed. 
The FQPA factor is removed because: a) the toxicology data base is
complete;  b) there is no indication of increased susceptibility of rats
or rabbits to in utero and/or postnatal exposure to glyphosate (in the
prenatal developmental toxicity study in rats, effects in the offspring
were observed only at or above treatment levels which resulted in
evidence of appreciable prenatal toxicity).

The use of generally high quality data, conservative models and/or
assumptions in the exposure assessment, provide adequate protection of
infants and children.]

	[Several maximum residue limits (MRLs) for glyphosate have been
established by CODEX in or on various commodities.  These limits are
based on the residue definition of glyphosate per se, without reference
to the cation used in product formulation. Based on toxicological
considerations,  EPA has determined that AMPA no longer needs to be
regulated and with this regulation has deleted AMPA from the U.S.
tolerance expression, so that the U.S. residue definition is harmonized
with that of CODEX. The proposed regulation amendment to include
applications of potassium glyphosate into  existing  U.S. tolerances
does not propose numerical changes, and the agreement between U.S.
tolerances and CODEX international residue standards is unaffected by
this action.]

 PAGE  12 

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{<E T=’03'>}

{</E>}

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{<E T=’03'>}

{</E>}

{<HD2>}

{</HD2>}

{<P>}