[Federal Register Volume 63, Number 34 (Friday, February 20, 1998)]
[Notices]
[Pages 8635-8644]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-4187]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-791; FRL-5768-9]


Notice of Filing of Pesticide Petitions

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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SUMMARY: This notice announces the initial filing of pesticide 
petitions proposing the establishment of regulations for residues of 
certain pesticide chemicals in or on various agricultural commodities.

DATES: Comments, identified by the docket control number PF-791, must 
be received on or before March 23, 1998.

ADDRESSES: By mail submit written comments to: Information and Records 
Integrity Branch, Public Information and Services Divison (7502C), 
Office of Pesticides Programs, Environmental Protection Agency, 401 M 
St., SW., Washington, DC 20460. In person bring comments to: Rm. 119, 
CM #2, 1921 Jefferson Davis Highway, Arlington, VA.
    Comments and data may also be submitted electronically by following 
the instructions under ``SUPPLEMENTARY INFORMATION.'' No confidential 
business information should be submitted through e-mail.
    Information submitted as a comment concerning this document may be 
claimed confidential by marking any part or all of that information as 
``Confidential Business Information'' (CBI). CBI should not be 
submitted through e-mail. Information marked as CBI will not be 
disclosed except in accordance with procedures set forth in 40 CFR part 
2. A copy of the comment that does not contain CBI must be submitted 
for inclusion in the public record. Information not marked confidential 
may be disclosed publicly by EPA without prior notice. All written 
comments will be available for public inspection in Rm. 119 at the 
address given above, from 8:30 a.m. to 4 p.m., Monday through Friday, 
excluding legal holidays.

FOR FURTHER INFORMATION CONTACT: By mail: James A. Tompkins, Product 
Manager (PM) 25, Registration Division, (7505C), Office of Pesticide 
Programs, Environmental Protection Agency, 401 M St., SW., Washington, 
DC 20460. Office location and telephone number: Rm. 239, 1921 Jefferson 
Davis Hwy., Arlington, VA., (703) 305-5697; e-mail: 
T[email protected].

SUPPLEMENTARY INFORMATION: EPA has received pesticide petitions as 
follows proposing the establishment and/or amendment of regulations for 
residues of certain pesticide chemicals in or on various raw 
agricultural commodities under section 408 of the Federal Food, Drug, 
and Comestic Act (FFDCA), 21 U.S.C. 346a. EPA has determined that these 
petitions contain data or information regarding the elements set forth 
in section 408(d)(2); however, EPA has not fully evaluated the 
sufficiency of the submitted data at this time or whether the data 
supports grantinig of the petition. Additional data may be needed 
before EPA rules on the petition.
    The official record for this notice, as well as the public version, 
has been established for this notice of filing under docket control 
number PF-791 (including comments and data submitted electronically as 
described below). A public version of this record, including printed, 
paper versions of electronic comments, which does not include any 
information claimed as CBI, is available for inspection from 8:30 a.m. 
to 4 p.m., Monday through Friday, excluding legal holidays. The 
official record is located at the address in ``ADDRESSES'' at the 
beginning of this document.
    Electronic comments can be sent directly to EPA at:
    [email protected]


    Electronic comments must be submitted as an ASCII file avoiding the 
use of special characters and any form of encryption. Comment and data 
will also be accepted on disks in Wordperfect 5.1/6.1 file format or 
ASCII file format. All comments and data in electronic form must be 
identified by the docket control number (insert docket number) and 
appropriate petition number. Electronic comments on this notice may be 
filed online at many Federal Depository Libraries.
    Authority: 21 U.S.C. 346a.

List of Subjects

    Environmental protection, Agricultural commodities, Food additives, 
Feed additives, Pesticides and

[[Page 8636]]

pests, Reporting and recordkeeping requirements.

    Dated: February 12, 1998.

Donald R. Stubbs,
Acting Director, Registration Division, Office of Pesticide Programs.

Summaries of Petitions

    Below summaries of the pesticide petitions are printed. The 
summaries of the petitions were prepared by the petitioners. The 
petition summary announces the availability of a description of the 
analytical methods available to EPA for the detection and measurement 
of the pesticide chemical residues or an explanation of why no such 
method is needed.

1. DowElanco

PP 1F3935

    EPA has received a pesticide petition (PP 1F3935) from DowElanco, 
9330 Zionsville Road, Indianapolis, IN 46268-1054 proposing pursuant to 
section 408(d) of the Federal Food, Drug and Cosmetic Act, 21 U.S.C. 
346a(d), to amend 40 CFR part 180 by establishing a tolerance for 
residues of triclopyr, (3,5,6-trichloro-2-pyridinyl)oxyacetic acid and 
its metabolites 3,5,6-trichloro-2-pyridinol (TCP) and 2-methoxy-3,5,6-
trichloropyridine (TMP) in or on the raw agricultural commodity fish at 
3.0 parts per million (ppm), and shellfish at 5.0 ppm. EPA has 
determined that the petition contains data or information regarding the 
elements set forth in section 408(d)(2) of the FFDCA; however, EPA has 
not fully evaluated the sufficiency of the submitted data at this time 
or whether the data supports granting of the petition. Additional data 
may be needed before EPA rules on the petition.

A. Residue Chemistry

    1. Analytical method. Adequate methodology is available for the 
enforcement of tolerances for triclopyr residues of concern. Gas 
chromatography methods are available for the determination of triclopyr 
residues of concern. Residues of triclopyr, 3,5,6-trichloro-2-
pyridinol, and 2-methoxy-3,5,6-trichloropyridine can be separately 
determined. The limits of quantitation are 0.01 - 0.05 ppm in fish and 
shellfish, depending on the compound being analyzed. The water method 
has a limit of quantitation of 0.1 parts per billion (ppb).
    2. Magnitude of residues. In field studies, triclopyr and its 
metabolites in water have half-lives of 0.5 - 15 days. Triclopyr 
residues in lake water treated at the maximum label rate were below 0.5 
ppm within 3 - 14 days. In pond water where whole ponds were treated at 
the maximum label rate, residues were below 0.5 ppm by 28 days after 
treatment. After 42 days in both lakes and ponds, residues were non-
detectable (<0.010 ppm) to 0.013 ppm.
    Residues of triclopyr and its metabolites 3,5,6-trichloro-2-
pyridinol and 2-methoxy-3,5,6-trichloropyridine reach a maximum 
concentration in fish at 3-14 days after treatment of water, and total 
residues of triclopyr and its metabolites were detectable in the edible 
flesh at a maximum level of 3.0 ppm in fish and 5.0 ppm in shellfish. 
Residues in fish and shellfish decline as residues in water dissipate.

B. Toxicological Profile

    1. Acute toxicity. The developmental no-effect level (NOEL) of 30 
milligrams/kilograms/day (mg/kg/day) from a rabbit developmental study 
was recommended for the acute dietary risk assessment. At the lowest 
effect level (LEL) of 100 mg/kg/day, there were embryotoxic and 
fetotoxic effects associated with significant maternal toxicity, 
including death. Acute exposure assessment will evaluate risk to 
pregnant females age 13 and older.
    2. Short- and Intermediate-Term Toxicity. Based on the available 
data, short- and intermediate-term dermal and inhalation risk 
assessments are not required. A systemic NOEL of 1,000 mg/kg/day, the 
highest dose tested (HDT), was determined in a 21-day dermal toxicity 
study in rabbits. The LC50 from the acute inhalation study 
in rats was determined to be > 2.6 mg/L (Toxicity Category III).
    3. Chronic toxicity. The Reference Dose (RfD) for triclopyr is 0.05 
mg/kg/day. This RfD is based on a 2-generation reproductive toxicity 
study in rats with a NOEL of 5.0 mg/kg/day using an uncertainty factor 
of 100. At the next higher dose level of 25 mg/kg/day, an increased 
incidence of slight degeneration of the proximal tubules of the kidneys 
was observed in some P1 and P2 parents of both sexes. Chronic exposure 
assessment will evaluate risk using this RfD.
    4. Carcinogenicity. Environmental Protection Agency's Cancer Peer 
Review Committee (CPRC) concluded that triclopyr should be classified 
as a ``Group D chemical'' - not classifiable as to human 
carcinogenicity. A cancer risk assessment is not required.
    5. Animal metabolism. Disposition and metabolism of 14C-
triclopyr in rats demonstrated that triclopyr was well absorbed after 
oral administration. Excretion was relatively rapid with a majority of 
radioactivity eliminated in the urine by 24 hours. At the high dose of 
60 mg/kg, urinary elimination of 14C-triclopyr was decreased 
due to apparent saturation of renal elimination mechanisms. Fecal 
elimination of 14C-triclopyr was a minor route of excretion, 
as was elimination via exhaled air. Unmetabolized parent chemical 
represented >90% of urinary radioactivity, with the remainder accounted 
for by the metabolite 3,5,6-trichloro-2-pyridinol (3,5,6-TCP), and 
possible glucuranide and/or sulfate conjugates of 3,5,6-TCP. Plasma 
elimination following intravenous administration of 14C-
triclopyr was consistent with a one-compartment model with an 
elimination half-life of 3.6 hr and zero-order kinetics from 0-12 hours 
at the 60 mg/kg dose.
    6. Bioequivalency. Toxicology studies conducted with triclopyr have 
been performed using both the free acid or the triethylamine salt from 
of triclopyr. Bioequivalency of the two chemical forms of triclopyr has 
been addressed through the conduct of special studies with the 
triethylamine from of triclopyr. These studies, which included data on 
comparative disposition, plasma half-life, tissue distribution, 
hydrolytic cleavage under physiological and environmental conditions 
for triclopyr triethylamine salt were found to adequately address the 
issue of Bioequivalency. In addition, subchronic toxicity studies 
supported the pharmacokinetics data in demonstrating bioequivalence. 
Therefore, studies conducted with any one from of triclopyr can be used 
to support the toxicology database as a whole.
    7. Endocrine effects. An evaluation of the potential effects on the 
endocrine systems of mammals has not been determined; However, no 
evidence of such effects were reported in the chronic or reproductive 
toxicology studies described above. There was no observed pathology of 
the endocrine organs in these studies. There is no evidence at this 
time that triclopyr causes endocrine effects.

C. Aggregate Exposure

    1. Dietary exposure. The RfD for triclopyr is based upon the 2-
generation reproduction toxicity study in rats with a NOEL of 5.0 mg/
kg/day, the lowest dose tested. An uncertainty factor of 10 for 
interspecies differences in response and an uncertainty factor of 10 
for intraspecies differences in response was applied. Thus, the RfD for 
triclopyr was established at 0.05 mg/kg/day by the RfD Peer Review 
Committee on September 4, 1996.
    A chronic dietary exposure analysis was performed using tolerance 
level

[[Page 8637]]

residues and 100 percent crop treated information to estimate the 
Theoretical Maximum Residue Contribution (TMRC) for the general 
population and 22 subgroups. Existing tolerances, including the 
proposed tolerances for fish and shellfish, result in a TMRC that 
represents 1.25% of the RfD for the U.S. general population. The 
highest subgroup, Non-Nursing Infants (<1 year old) occupies 2.65% of 
the RfD. The chronic analysis for triclopyr is a worse case estimate of 
dietary exposure with all residues at tolerance level and 100 percent 
of the commodities assumed to be treated with triclopyr. Based on the 
risk estimates calculated in this analysis, the chronic dietary risk 
from the uses currently registered is not of concern.
    Since the toxicological endpoint to which exposure is being 
compared in the acute dietary risk analysis is a developmental NOEL (30 
mg/kg/day), females (13+ years) are the sub population of particular 
interest. The Margin of Exposure (MOE) is a measure of how close the 
high end exposure comes to the NOEL (the highest dose at which no 
effects were observed in the laboratory test), and is calculated as the 
ratio of the NOEL to the exposure (NOEL/exposure = MOE.) Generally, 
acute dietary margins of exposure greater than 100 tend to cause no 
dietary concern. The high end MOE value of 1,639 is above the 
acceptable level and demonstrates no acute dietary concern.
    An acute dietary exposure analysis was performed using tolerance 
level residues and 100 percent crop treated to estimate the high end 
exposure for the general population and females (13+, pregnant, non-
nursing). The high end exposure was assumed to be the upper 0.5% of 
consumers, that is, the 99.5 percentile. The resulting exposure 
estimates and margins of exposure are as follows:


                                                                        
------------------------------------------------------------------------
                                  Exposure (mg/kg BW/                   
       Population Subgroup               day)                 MOE       
------------------------------------------------------------------------
U.S. Population                   0.01359             2208              
Females                           0.01831             1639              
------------------------------------------------------------------------


    These high end MOE values are above the acceptable level and 
demonstrate no acute dietary concerns.

    2. Drinking water. The use of triclopyr as described on the label 
allows only slight additional exposure of triclopyr to humans. The 
proposed labeling requires that the product not be applied within one-
quarter mile of a potable water intake and that treated water not be 
used for domestic purposes until the residue level is demonstrated to 
be at or below 0.5 ppm as determined by laboratory analysis or 
immunoassay. The basis for these restrictions is a series of aquatic 
dissipation studies conducted in lakes and ponds. In these studies, 
triclopyr was applied to lakes and ponds at the maximum concentration 
of 2.5 ppm triclopyr in water. Triclopyr residues in the lakes at one-
quarter mile from the treatment areas were well below 0.1 ppm 
throughout the study, with a maximum reported value of 0.058 ppm. 
Within the treatment area, triclopyr residues of less than 0.5 ppm were 
reported at 3 - 14 days after treatment in the Lake Minnetonka and Lake 
Seminole studies. In seven test ponds treated with triclopyr at a water 
concentration of 2.5 ppm, total residues of triclopyr were less than 
0.5 ppm by 28 days after application, with the highest residue value 
being 0.193 ppm. At 42 days after treatment, total residues in both 
treated lakes and ponds ranged from non-detectable to 0.013 ppm.
    If the proposed labeling is followed precisely, that is, potable 
water is not collected within one-quarter mile of a treated area, there 
will be little contribution from water to the ``risk cup'' for 
triclopyr. If drinking water is collected from the treatment area when 
water analysis indicates triclopyr residues are 0.5 ppm or less, the 
risk is still acceptable on an acute basis. On a chronic basis, the 
value of 0.013 ppm, found to be the highest triclopyr residue at 42 
days after treatment in all studies, uses only 0.9% of the RfD for 
females (13+, pregnant, not nursing) and 2.6% of the RfD for children 
(1-6 years).
    For a worst case estimate of potential drinking water exposure, the 
water residue at the proposed allowable water level at 0.5 ppm was 
utilized. When this residue level is considered, the following analysis 
indicates no level of concern for acute exposure:
    For a 60 kg pregnant female consuming 2 liters a day (Acute)
    (0.5 mg/L  x  2 L/day) / 60 kg = 0.0167 mg/kg/day
    MOE = NOEL / Exposure = (30 mg/kg/day) / ( 0.0167 mg/kg/day) = 
1796


    For a 60 kg pregnant female consuming 2 liters a day (Chronic)
    (0.013 mg/kg/day  x  2 L/day) / 60 kg = 0.00043 mg/kg/day
    % RfD = (0.00043 mg/kg/day  x  100) / (0.05 mg/kg/day) = 0.9 %


    For a 10 kg child consuming 1 liter a day (Acute)
    (0.5 mg/L  x  1 L/day) / 10 kg = 0.05 mg/kg/day
    MOE = (30 mg/kg/day) / (0.05 mg/kg/day) = 600


    For a 10 kg child consuming 1 liter a day (Chronic)
    (0.013 mg/L  x  1 L/day) / 10 kg = 0.0013 mg/kg/day
    % RfD = (0.0013 mg/kg/day  x  100) / (0.05 mg/kg/day) = 2.6 %


    3. Non-dietary exposure. There are potential exposures to 
homeowners during usual use-patterns associated with triclopyr. These 
involve application of triclopyr-containing products by means of 
aerosol cans, pump spray bottles, squeeze bottles, ``weed sticks,'' 
hose-end sprayers, power sprayers, paint brush, rotary and drop 
spreaders. It is unlikely that power sprayers will be used by 
homeowners; this is an application method requiring special applicator 
equipment more apt to be used by agricultural or commercial applicator.
    Homeowner exposure will not be significant for the following 
reasons: the percent ai in products for homeowner use is less than that 
for agricultural or industrial use; the areas treated are usually 
limited in size; all products are intended for outdoor use which is 
likely to reduce the concentration in the environment by allowing 
dissipation in the outdoor air; the application methods recommended or 
commonly used by homeowners are not expected to provide significant 
exposure. Additionally, no toxicological endpoints of concern have been 
identified by EPA for dermal exposure to triclopyr, therefore, no 
exposure assessment is required for this exposure; an inhalation 
exposure assessment is also not required and no chronic use pattern is 
expected for homeowner use of triclopyr products.
    There is a potential for post-application exposure to swimmers 
following applications to aquatic sites

[[Page 8638]]

that may be used for recreational purposes. There are no triclopyr-
specific exposure data to assess swimmer exposure. However, an 
assessment was conducted using information provided in EPA's Dermal 
Exposure Assessment: Principles and Applications. The dermal 
permeability constant (Kp) was calculated to be 6.5  x  10-8 
mg/cm2/hr. The assessment of swimmer exposure was based on a 
six-year old boy having a body weight of 21.9 kg and a surface area of 
0.88 m2. The swimming period was assumed to be 3 hours on 
the day of treatment in water containing 2.5 ppm triclopyr.
    Total dermal exposure (mg) = 3 hr/day  x  0.88 m2  x  
104 cm2/m2  x  6.5  x  10-8 mg/
cm2/hr = 1.716  x  10-3 mg/day
    Oral absorption could also account for a portion of the exposure. 
It was assumed that 1% of the water in residence in the mouth while 
breathing will be swallowed.
    Oral exposure = 3 hr/day  x  0.05 L/hr  x  2.5 mg/L = 0.375 mg/day
    Combining the dermal exposure and oral exposure for a 21.9 kg 
child, the swimming exposure for one day was estimated to be 0.377 mg/
day  21.9 kg = 0.017 mg/kg/day. Compared to the acute NOEL of 
30 mg/kg/day, an MOE of 1,765 was obtained. No dermal or inhalation 
endpoint has been established for triclopyr, so this represents a very 
conservative estimate of the risk due to swimming in triclopyr-treated 
waters.

D. Cumulative Effects

    The potential for cumulative effects of triclopyr and other 
substances that have a common mechanism of toxicity was considered. The 
mammalian toxicity of triclopyr is well defined. However, the 
biochemical mechanism of toxicity of this compound is not known. No 
reliable information exists to indicate that toxic effects produced by 
triclopyr would be cumulative with those of other similar compounds. 
Therefore, consideration of a common mechanism of toxicity with other 
compounds is not appropriate. Thus, only the potential risks of 
triclopyr are considered in the aggregate exposure assessment.

E. Safety Determination

    1. U.S. population. Because of the toxicological characteristics of 
triclopyr (no dermal endpoint of concern), post-application exposure 
assessment was not necessary. Residential exposure is considered to be 
negligible. Swimming in treated water was shown to be a minimal risk. 
Therefore, residential and swimming exposure were not considered in the 
aggregate risk calculation.
    For the population subgroup of concern, pregnant females age 13 and 
older, an MOE of 857 was estimated for the acute aggregate dietary risk 
(food + water) from exposures to triclopyr residues.
    MOE = (30 mg/kg/day) / (0.0183 + 0.0167) mg/kg/day = 857
    Using the TMRC exposure assumptions described above, the percentage 
of the RfD that will be utilized by aggregate exposures (food + water) 
to residues of triclopyr ranges from 2.1% to 5.3% for the U.S. 
population. The major identifiable subgroup with the highest aggregate 
exposure is non-nursing infants <1 year old. The water exposure value 
used the highest water residue concentration at 42 days after treatment 
of lakes and ponds (the longest sampling time interval common to all 
studies), 0.013 ppm, in the calculations below:
    Total U.S. Population (Dietary + Drinking Water)
    (0.00062 + 0.00043) mg/kg/day  x  100 / (0.05 mg/kg/day) = 2.1% 
Rfd


    Non-nursing Infants (Dietary + Drinking Water)
    (0.00133 + 0.0013) mg/kg/day  x  100 / (0.05 mg/kg/day) = 5.3% 
Rfd


    Determination of Safety for U.S. Population
    Based on the current state of knowledge for this chemical, the 
RfD approach accurately reflects the exposure of the U.S. 
population, infants and children to triclopyr.


    2. Infants and children. Studies cited earlier in this document 
indicate that triclopyr is not a selective developmental toxicant, and 
an additional uncertainty factor for infants and children is 
unnecessary. This decision is based on the following data.
    Since the developmental and reproductive NOELs were either the same 
or greater than the maternal or parental, it is unlikely that there is 
additional risk concern for immature or developing organisms which is 
not reflected by the risk assessment utilizing the established 
reference dose. The effects noted for the RfD NOEL are parental 
effects, not developmental.

F. International Tolerances

    There are no established or proposed Codex MRLs for triclopyr 
residues. Therefore, there are no issues of compatibility with respect 
to U.S. tolerances and Codex MRLs.

2. E.I. du Pont de Nemours & Company

PP 6F4706

    EPA has received a pesticide petition (PP 6F4706)from E.I. du Pont 
de Nemours & Company, Barley Mill Plaza, P.O. Box 80038, Willimington, 
DE 19880-0038. proposing pursuant to section 408(d) of the Federal 
Food, Drug and Cosmetic Act, 21 U.S.C. 346a(d), to amend 40 CFR part 
180 by establishing a tolerance for residues of rimsulfuron: N-((4,6-
dimethoxypyrimidin-2-yl) aminocarbonyl) -3- (ethylsulfonyl) -2-
pyridinesulfonamide in or on the raw agricultural commodity tomato 
fruit at 0.10 parts per million. EPA has determined that the petition 
contains data or information regarding the elements set forth in 
section 408(d)(2) of the FFDCA; however, EPA has not fully evaluated 
the sufficiency of the submitted data at this time or whether the data 
supports granting of the petition. Additional data may be needed before 
EPA rules on the petition.

A. Residue Chemistry

    1. Plant metabolism. With the initial establishment of rimsulfuron 
tolerances in field corn and potatoes, the EPA determined that the 
nature of plant residues was adequately understood for the purposes 
establishing those tolerances. A metabolism study on tomatoes was 
conducted at the following use rates:


                                                                                                                                                                                                                                        
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                                                                                                                        
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Tomatoes grown in field..........                                                                                                             72 g active ingredient per hectare (approx. 1 oz. ai per acre, maximum proposed use rate).
Tomatoes grown in greenhouse.....                                                                               172, 350, and ca. 700 g ai per hectare (2.5, 5, and 10 oz. ai per acre or up to 10 times the proposed maximum use rate).
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------



[[Page 8639]]

    No residues of rimsulfuron or any metabolite were detected in any 
tomato fruit, immature or mature. Detection limits for the study were 
0.004 ppm for the field-grown samples and 0.013 ppm for the greenhouse-
grown samples. This study conclusively shows that application of 
rimsulfuron to tomatoes, when used in accordance with the proposed 
label directions, will not result in detectable residue of rimsulfuron 
or its metabolites in tomato fruit. Therefore, the nature of 
rimsulfuron residues (i.e., their absence) has been established for 
tomato fruit, the only raw agricultural commodity established for 
tomatoes.
    2. Analytical method. Adequate analytical methodology, high-
pressure liquid chromatography with Uv detection, is available for 
enforcement purposes. The method is ``Analytical Method for the 
Quantitiation of DPX-E9636 (rimsulfuron) in Various Crop Matrices and 
Their Processed Fractions'', DuPont Report No. AMR 3424-95, EPA MRID 
No. 43979002. The method involves liquid chromatography utilizing 
eluent and column switching with UV/VIS detection at 254 nm. The limit 
of quantitation for rimsulfuron in tomatoes is 0.05 ppm. EPA offers 
enforcement methodology to anyone interested in pesticide enforcement 
when requested by mail from: Calvin Furlow, Public Response and Program 
Resources Branch, Field Operations Division (7506C), Office of 
Pesticide Programs, Environmental Protection Agency, 401 M St., SW., 
Washington, DC 20460. Office location and telephone number: Rm. 1130A, 
CM#2, 1921 Jefferson Davis Hwy., Arlington, VA 22202.
    3. Magnitude of residues. --i. Plant residues. Magnitude of 
residues of rimsulfuron in tomato fruit were determined following 
application of rimsulfuron at the proposed maximum annual use rate of 
1.0 oz ai/acre (1 x ), and at twice that rate (2 x ). An additional 
test was conducted at an exaggerated rate of 5.0 oz ai/acre (5 x ) in 
an attempt to generate quantifiable residues in tomato fruit (RAC) for 
a processing study.
    Seventeen tests, each containing one control and two treatment 
plots, were established in California, Florida, Indiana, Maryland, and 
Pennsylvania. Row-crop tomato samples were collected approximately 45 
days following the final application; staked tomatoes were collected 
immediately following the final application. Tomato samples were 
analyzed using the procedures described in DuPont Method No. AMR 3424-
95, Analytical Method for the Quantitation of DPX-E9636 in Various Crop 
Matrices and Their Processed Fractions. The overall mean percent 
recovery of 52 control tomato samples fortified at either 0.05 or 0.10 
ppm was 86%, with a relative standard deviation of 4%. Results of 
freezer storage stability study indicate that rimsulfuron is stable up 
to 6 months in tomatoes stored at -20C +/- 5C.
    No quantifiable residues (<0.05 ppm) of rimsulfuron were found in 
any of the tomato samples treated at 1.0, 2.0, and 5.0 oz ai/acre. A 
processing study was not necessary since all 1 x  and 5 x  samples did 
not have rimsulfuron present with a limit of quantitation of 0.05 ppm.
    Data generated from this study support the use of rimsulfuron on 
tomatoes at a maximum seasonal use rate of 1.0 oz ai/acre with a 
minimum preharvest interval of 45 days. Study results also support the 
petition for a 0.10 ppm tolerance of rimsulfuron on tomatoes.
    ii. Animal residues. EPA determined, upon granting field corn and 
potato tolerances, that there is no reasonable expectation of residues 
occurring in meat, milk, poultry, or eggs from these tolerances. Tomato 
fruit and its processed commodities (i.e., tomato paste and puree) are 
not considered by the EPA to be animal feed items. Further, no residues 
would be available to enter animal feed based on results from the 
tomato metabolism study and magnitude or residue study discussed above. 
Therefore, there remains a reasonable expectation that no residue of 
rimsulfuron will occur in meat, milk, poultry, or eggs from all 
rimsulfuron tolerances, current (field corn and potatoes) and proposed 
(tomatoes).

B. Toxicological Profile

    1. Acute toxicity. Technical rimsulfuron has been placed in acute 
toxicology category III based on overall results from several studies. 
This compound was placed in toxicology category III for acute dermal 
toxicity (LD50 > 2,000 mg/kg; rabbits) and eye irritation 
(effects reversible within 72 hours; rabbits). Acute oral toxicity 
(LD50 > 5,000 mg/kg; rats), acute inhalation toxicity 
(LC50 > 5.4 mg/L, rats) and skin irritation (no observed 
irritation; rabbits) results were assigned toxicology category IV. 
Technical rimsulfuron is not a dermal sensitizer.
    2. Genotoxicty. Technical rimsulfuron was negative for genotoxicity 
in a battery of in vitro and in vivo tests. These tests included the 
following: mutagenicity in bacterial (Ames test) and mammalian (CHO/
HGPRT assay) cells; in vitro cytogenetics (chromosomal aberration in 
human lymphocytes); in vivo cytogenetics (bone marrow micronucleus 
assay in mice); and unscheduled DNA synthesis in rat primary 
hepatocytes.
    3. Reproductive and developmental toxicity. A two-generation 
reproduction study was conducted in rats with dietary technical 
rimsulfuron concentrations of 0, 50, 3,000 or 15,000 ppm. The study was 
negative for reproductive toxicity and there was no indication that 
offspring were more susceptible to rimsulfuron administration than 
parents. The NOEL was 3,000 ppm (or 165 to 264 mg/kg/day for P1 and F1 
males and females and their offspring). This was based on the following 
effects at 15,000 ppm (830 to 1,316 mg/kg/day): lower food consumption 
and/or food efficiency in P1 males and females and F1 females; 
decreased mean body weights and/or body weight gain by P1 and F1 males 
and females; lower mean body weights and increased incidence of small 
body size for F2 pups during lactation.
    A developmental study was conducted in rats administered technical 
rimsulfuron by gavage at 0, 200, 700, 2,000 or 6,000 mg/kg/day. There 
were no systemic or developmental effects observed up to and including 
the highest dose tested. The NOEL was therefore > 6,000 mg/kg/day.
    A developmental study was conducted in rabbits administered 
technical rimsulfuron by gavage at 0, 25, 170, 500 or 1,500 mg/kg/day. 
The NOELs for maternal and offspring toxicity were 170 and 500 mg/kg/
day, respectively. The maternal NOEL was based on reduced body weight 
and mortality at higher doses. These maternal effects precluded any 
evaluation of adverse effects in fetuses at 1,500 mg/kg/day; however, 
there were no systemic or developmental effects observed among fetuses 
at 500 mg/kg/day and below.
    4. Subchronic toxicity. A 90-day study in mice was conducted at 
dietary concentrations of 0, 50, 375, 1,500 or 7,500 ppm. The NOELs 
were 375 ppm (56.0 mg/kg/day) for male mice and 7,500 ppm (1,575 mg/kg/
day) for female mice. The NOEL for males was based on slight reductions 
in mean body weight gain and food efficiency at 1,500 ppm (228 mg/kg/
day).
    Technical rimsulfuron was administered in the diets of rats at 0, 
50, 1,500, 7,500 or 20,000 ppm for 90 days. The NOEL was 1,500 ppm (102 
and 120 mg/kg/day for males and females, respectively) based on reduced 
mean body weights and body weight gains and increased relative liver 
weights at

[[Page 8640]]

7,500 ppm (495 and 615 mg/kg/day for males and females, respectively).
    Dogs were administered technical rimsulfuron in their diets at 0, 
250, 5,000 or 20,000 ppm for 90 days. The NOEL was 250 ppm (9.63 and 
10.6 mg/kg/day for males and females, respectively). This was based on 
slight increases in liver and/or kidney weights, increased urine volume 
and decreased urine osmolarity at 5,000 ppm (193 and 189 mg/kg/day for 
males and females, respectively).
    5. Chronic toxicity. An 18-month mouse study was conducted with 
dietary concentrations of 0, 25, 250, 2,500 or 7,500 ppm technical 
rimsulfuron. This product was not oncogenic in mice. The systemic NOEL 
was 2,500 ppm (351 and 488 mg/kg/day for males and females, 
respectively) based on decreased mean body weights in both sexes and 
increased incidence of spontaneous, age-related artery and tunica 
degeneration in the testes for this mouse strain at the highest dose 
tested, 7,500 ppm (1,127 and 1,505 mg/kg/day for males and females, 
respectively). The latter was observed in the absence of any effect on 
spermatogenesis. An increased incidence of dilation and cysts in the 
glandular stomach of males was also observed at 7,500 ppm.
    A 2-year chronic toxicity/oncogenicity study was conducted in rats 
fed diets that contained 0, 25, 300, 3,000 or 10,000 ppm technical 
rimsulfuron. This product was not oncogenic in rats. The systemic NOELs 
were 300 ppm (11.8 mg/kg/day) for males and 3,000 ppm (163 mg/kg/day) 
for females. The NOELs were defined by decreased body weight gain and 
increased relative liver weights at 3,000 ppm (121 mg/kg/day) and 
10,000 ppm (569 mg/kg/day) for males and females, respectively.
    Technical rimsulfuron was administered for one year to dogs at 
dietary concentrations of 0, 50, 2,500 or 10,000 ppm. The NOELs were 50 
ppm (1.6 mg/kg/day) for males and 2,500 ppm (86.5 mg/kg/day) for 
females. The NOEL for males was based on the following effects observed 
at 2,500 ppm (81.8 mg/kg/day): increased absolute liver and kidney 
weights; and increased incidence of seminiferous tubule degeneration 
and increased numbers of spermatid giant cells present in the 
epididymides. The NOEL for females was based on the following effects 
observed at 10,000 ppm (358.5 mg/kg/day): decreased body weight and 
body weight gain; increased serum cholesterol levels and alkaline 
phosphatase activity, increased absolute liver weight and increased 
relative liver and kidney weights.
    6. Animal metabolism. The metabolism of rimsulfuron in animals 
(rat, goat and hen) is adequately understood and is similar among the 
species evaluated. Rimsulfuron was rapidly eliminated via urinary and 
fecal excretion in the rat. Approximately 60 to 70% of the administered 
dose to rats was excreted within 24 hours. There were no volatile 
metabolites detected and unmetabolised rimsulfuron was the major 
component in the urine (42 - 55%) and feces (5 - 16%). The major 
metabolic pathway in rats involved a contraction of the sulfonylurea 
bridge followed by dealkylation, hydroxylation and/or conjugation 
reactions. Cleavage of the sulfonylurea bridge was observed; however, 
it was considered to be a minor pathway. Elimination of administered 
rimsulfuron was similarly rapid for the goat and hen. Tissue residue 
levels were generally less than 0.3% of the administered dose for the 
rat, goat and hen. There was no evidence of accumulation of rimsulfuron 
or its metabolites in tissues of any of the species or in milk and 
eggs.
    7. Metabolite toxicology. Common metabolic pathways for rimsulfuron 
were demonstrated in the rat, goat and hen as well as plants (corn, 
tomatoes and potatoes). When evaluated for acute toxicity and 
mutagenicity, two of the major metabolites, i.e., one resulting from 
contraction of the sulfonylurea bridge and one from the cleavage of 
this bridge, were found to be of low toxicity and were negative in the 
Ames test. The existing metabolism studies indicate that the 
metabolites formed are unlikely to accumulate in humans or in animals 
that may be exposed to these residues in the diet. The fact that no 
quantifiable residues were found in treated crops further indicates 
that exposures to and accumulation of metabolites are unlikely. Because 
of the above, toxicology studies on metabolites were not required.

C. Aggregate Exposure

    1. Dietary exposure -- Residue of concern. When tolerances were 
established on field corn and potatoes, EPA determined that the residue 
of concern was rimsulfuron. The metabolism study conducted on tomatoes 
(see Plant Metabolism Section) showed no residues of rimsulfuron are 
present in the tomato fruit. Therefore, the residue of concern 
continues to be rimsulfuron.
    2. Food. For the general U.S. population, acute dietary exposure 
assessments were not considered relevant for rimsulfuron for the 
following reasons: rimsulfuron presents very low acute toxicity based 
on animal testing; and no detectable residues have been demonstrated in 
edible portions of treated crops.
    The Agency has conducted chronic dietary exposure assessments for 
rimsulfuron and the results are summarized below. The Reference Dose 
(RfD) is based on a NOEL of 1.6 mg/kg/day established in the 1-year 
feeding study with dogs and combines an uncertainty factor of 100. EPA 
calculated the RfD to be 0.016 mg/kg/day. The theoretical maximum 
residue contribution (TMRC) for these tolerances for the overall U.S. 
population is 1.47  x  10-4 mg/kg/day or 0.92% of the RfD 
based on current (field corn and potatoes) tolerances and would be 2.21 
 x  10-4, or 1.4% of the RfD when the proposed tolerance on 
tomatoes is included.
    For infants and children, the TMRC for the most exposed subgroup, 
children (1 to 6 years old), is 2.37  x  10-4 mg/kg/day, 
respectively, or 1.95% of the RfD based on current (field corn and 
potatoes) tolerances and would be 4.37  x  10-4 mg/kg/day, 
or 2.73% of the RfD, when the proposed tomato tolerance is included. As 
with calculations for the general US population, these values assume 
the residues are at the established tolerance level and that 100 
percent of the crop is treated.
    3. Drinking water. Another potential dietary source of exposure of 
the general population to residues of pesticides is residues in 
drinking water. There have been no field studies or monitoring programs 
conducted to assess rimsulfuron residues in groundwater or drinking 
water. Several factors indicate very low potential that rimsulfuron 
will be present in raw or finished drinking water: low use rate (1 oz 
a.i./acre), rapid hydrolysis (half-life < 7 days), short half-lives 
under field conditions (7-18 days), absence of leaching in field soil 
dissipation studies. Water solubility for rimsulfuron is as follows:


[[Page 8641]]



                                                                                                                                                                                                
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                                                                                
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Unbuffered Water:...........................                                                                                                                                            < 10 ppm
Buffers:....................................  pH 5                                                                                                                                       135 ppm
  ..........................................  pH 7                                                                                                                                     7,300 ppm
  ..........................................  pH 9                                                                                 5,560 ppm (rapidly decomposes at pH 9); Koc is less than 100.
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

    Computer modeling, taking into account use rate, physical 
properties, and degradation rates, predicts low probability of 
rimsulfuron being present in ground- or drinking water. Given that only 
2.73% of the RfD is attained by the TMRC for the population sub-group 
with the highest theoretical dietary exposure (children 1-6 years old; 
see above), there is ample allowance for safe exposure to rimsulfuron 
via drinking water.
    4. Non-dietary exposure. Rimsulfuron is not registered for any use 
which could result in non-occupational, or non-dietary exposure to the 
general population.

D. Cumulative Effects

    Rimsulfuron belongs to the sulfonylurea class of crop protection 
chemicals. Other structurally similar compounds in this class are 
registered herbicides. However, the herbicidal activity of 
sulfonylureas is due to the inhibition of acetolactate synthase (ALS), 
an enzyme found only in plants. This enzyme is part of the biosynthesis 
pathway leading to the formation of branched chain amino acids. Animals 
lack ALS and this biosynthetic pathway. This lack of ALS contributes to 
the relatively low toxicity of sulfonylurea herbicides in animals. 
There is no reliable information that would indicate or suggest that 
rimsulfuron has any toxic effects on mammals that would be cumulative 
with those of any other chemical.

E. Safety Determination

    1. U.S. population. Based on the completeness and reliability of 
the toxicology database and using the conservative assumptions 
presented earlier, EPA has established an RfD of 0.016 mg/kg/day. This 
was based on the NOEL for the 1-year dog study of 1.6 mg/kg/day and 
employed a 100-fold uncertainty factor. It has been concluded that the 
aggregate exposure for existing crops (corn and potatoes) would utilize 
0.92% of the RfD and that the addition of tomatoes would increase 
utilization to 1.4% of the RfD. Generally, exposures below 100% of the 
RfD are of no concern because it represents the level at or below which 
daily aggregate dietary exposure over a lifetime will not pose 
appreciable risk to human health. Thus, there is reasonable certainty 
that no harm will result from aggregate exposures to rimsulfuron 
residues.
    2. Infants and children. In assessing the potential for additional 
sensitivity of infants and children to residues of rimsulfuron, data 
from the previously discussed developmental and multigeneration 
reproductive toxicity studies were considered.
    Developmental studies are designed to evaluate adverse effects on 
the developing organism resulting from pesticide exposure during pre-
natal development. Reproduction studies provide information relating to 
reproductive and other effects on adults and offspring from pre-natal 
and post-natal exposures to the pesticide. The studies with rimsulfuron 
demonstrated no evidence of developmental toxicity at exposures below 
those causing maternal toxicity. This indicates that developing animals 
are not more sensitive to the effects of rimsulfuron administration 
than adults.
    FFDCA section 408 provides that EPA may apply an additional 
uncertainty factor for infants and children in the case of threshold 
effects to account for pre- and post-natal toxicity and the 
completeness of the database. Based on current toxicological data 
requirements, the database for rimsulfuron relative to pre- and post-
natal effects for children is complete. In addition, the NOEL of 1.6 
mg/kg/day in the 1-year dog study and upon which the RfD is based is 
much lower than the NOELs defined in the reproduction and developmental 
toxicology studies. Conservative assumptions utilized to estimate 
aggregate dietary exposures of infants and children to rimsulfuron 
demonstrated that only 1.95% of the RfD was utilized for current 
tolerances (corn and potatoes) and the addition of tomatoes would only 
increase utilization to 2.73% of the RfD for the highest exposed group. 
Based on these exposure estimates and the fact that the current 
database demonstrates that the developing offspring or young animals 
are not uniquely susceptible to rimsulfuron administration, the extra 
10-fold uncertainty factor is not warranted for these groups. 
Therefore, it may be concluded that there is reasonable certainty that 
no harm will result to infants and children from aggregate exposures to 
rimsulfuron.

F. International Tolerances

    The following international tolerances (or Maximum Residue Levels, 
MRL's) exist:


                                                                                                                
----------------------------------------------------------------------------------------------------------------
             Country                 Tolerance in ppm                             Crop                          
----------------------------------------------------------------------------------------------------------------
Australia                          0.05                                                                 Tomatoes
Austria                            0.1                                                              Corn, Potato
Belgium                            0.05                                                                     Corn
Bulgaria                           0.5                                                               Corn-Fodder
Canada                             0.1                                                              Corn, Potato
Croatia                            0.1                                                                    Fodder
Czech. Rep.                        0.05                                                      Corn, Grain, Potato
Germany                            0.05                                                             Corn, Potato
Hungary                            0.2                                                                      Corn
Italy                              0.10                                                   Corn, Potato, Tomatoes
Romania                            0.05                                                             Corn, Potato

[[Page 8642]]

                                                                                                                
Slovakia                           0.05                                                              Corn, Grain
Spain                              0.05                                                           Corn, Tomatoes
United States                      0.1                                                              Corn, Potato
----------------------------------------------------------------------------------------------------------------


3. Monsanto Company

PP 2E4118 and 7F4886

    EPA has received a pesticide petitions (PP 2E4118 and 7F4886) from 
Monsanto Company, 700 14th St.,NW., Suite 1100, Washington, D.C. 20005, 
proposing pursuant to section 408(d) of the Federal Food, Drug and 
Cosmetic Act, 21 U.S.C. 346a(d), to amend 40 CFR part 180 to establish 
an exemption from the requirement of a tolerance for glyphosate [(N-
phosphonomethyl) glycine] in or on the imported raw agricultural 
commodities barley grain at 20 parts per million (ppm); barley, bran 
and pearled barley at 60 ppm; cereal grains group (except wheat, corn, 
oats, grain sorghum, and barley at 0.1 ppm; canola, seed at 10 ppm; 
canola, meal at 25 ppm; legume vegetables (succulent or dried) group 
(except soybeans) at 5 ppm. (PP 2E4118) and in or on the raw 
agricultural commodities beets, sugar, tops (leaves) at 10 ppm; beets, 
sugar, root at 10 ppm; and beets, sugar, pulp, dried at 25 ppm (PP 
7F4886). EPA has determined that the petition contains data or 
information regarding the elements set forth in section 408(d)(2) of 
the FFDCA; however, EPA has not fully evaluated the sufficiency of the 
submitted data at this time or whether the data supports granting of 
the petition. Additional data may be needed before EPA rules on the 
petition.

A. Residue Chemistry

    1. Plant metabolism. The nature of the residue in plants is 
adequately understood and consists of the parent, glyphosate and its 
metabolite AMPA (aminomethyl-phosphonic acid). Only glyphosate parent 
is to be regulated in plant and animal commodities since the metabolite 
AMPA is not of toxicological concern in food.
    2. Analytical method. Adequate methodology High Pressure Liquid 
Chromatograpy (HPLC) with fluorometric detection is available for 
enforcement purposes, and the methodology has been published in the 
Pesticide Analytical Manual (PAM), Vol. II. This method has a limit of 
detection (0.05 ppm) that allows monitoring of food with residues at or 
above the levels set in these tolerances.
    3. Magnitude of residues. The submitted residue data adequately 
support the proposed tolerances on Barley, grain (20 ppm); Barley, bran 
and pearled barley (60 ppm); Canola, seed (10 ppm); Canola, meal (25 
ppm); and Legume vegetables (succulent or dried) group (except 
soybeans) (5 ppm), Sugar beet roots at 10 ppm, Sugar beet tops at 10 
ppm and Sugar beet dried pulp at 25 ppm. Any secondary residues 
occurring in liver or kidney of cattle, goats, horses, and sheep and 
liver and kidney of poultry will be covered by existing tolerances.

B. Toxicological Profile

    1. Acute toxicity. A rat acute oral study with a combined 
LD50 of > 5000 mg/kg.
    A rabbit acute dermal LD50 of > 5000 mg/kg.
    A primary eye irritation study in the rabbit which showed severe 
irritation for glyphosate acid. However, glyphosate is normally 
formulated as one of several salts and eye irritation studies on the 
salts showed essentially no irritation.
    A primary dermal irritation study which showed essentially no 
irritation.
    A primary dermal sensitization study which showed no sensitization.
    2. Genotoxicty. A number of mutagenicity studies were conducted and 
were all negative. These studies included: chromosomal aberration in 
vitro (no aberrations in Chinese hamster ovary cells were caused with 
or without S9 activation); DNA repair in rat hepatocyte; in vivo bone 
marrow cytogenic test in rats; rec-assay with B. subtilis; reverse 
mutation test with S. typhimurium; Ames test with S. typhimurium; and 
dominant-lethal mutagenicity test in mice.
    3. Reproductive and developmental toxicity. An oral developmental 
toxicity study with rats given doses of 0, 300, 1,000 and 3,500 mg/kg/
day with a maternal no observable effect level (NOEL) of 1,000 mg/kg/
day based on clinical signs of toxicity, body weight effects and 
mortality, and a fetal NOEL of 1,000 mg/kg/day based on reduced body 
weights and delayed sternebrae maturation at the highest dose tested of 
3,500 mg/kg/day.
    An oral developmental toxicity study with rabbits given doses of 0, 
75, 175 and 350 mg/kg/day with a maternal of NOEL of 175 mg/kg/day 
based on clinical signs of toxicity and mortality, and a fetal NOEL of 
350 mg/kg/day based on no developmental toxicity at any dose tested.
    A 3-generation reproduction study with rats fed dosage levels of 0, 
3, 10 and 30 mg/kg/day with a NOEL for systemic and reproductive/
developmental parameters of 30 mg/kg/day based on no adverse effects 
noted at any dose level.
    A 2-generation reproduction study with rats fed dosage levels of 0, 
100, 500 and 1,500 mg/kg/day with a NOEL for systemic and developmental 
parameters of 500 mg/kg/day based on body weight effects, clinical 
signs of toxicity in adult animals and decreased pup bodyweights, and a 
reproductive NOEL of 1,500 mg/kg/day.
    4. Subchronic toxicity. A 90-day feeding study in rats fed dosage 
levels of 0, 1,000, 5,000 and 20,000 ppm with a NOEL of 20,000 ppm 
based on no effects even at the highest dose tested.
    A 90-day feeding study in mice fed dosage levels of 0, 5,000, 
10,000 and 50,000 with a NOEL of 10,000 ppm based on body weight 
effects at the high dose.
    A 90-day feeding study in dogs given glyphosate, via capsule, at 
doses of 0, 200, 600 and 2,000 mg/kg/day with a NOEL of 2,000 mg/kg/day 
based on no effects even at the highest dose tested.
    5. Chronic toxicity. A 12-month oral study in dogs given 
glyphosate, via capsule, at doses of 0, 20, 100 and 500 mg/kg/day with 
a NOEL of 500 mg/kg/day based on no adverse effects at any dose level.
    A 26-month chronic/feeding oncogenicity study with rats fed dosage 
levels of 0, 3, 10 and 31 mg/kg/day (males) and 0, 3, 11 and 34 mg/kg/
day (females) with a systemic NOEL of 31 mg/kg/day (males) and 34 mg/
kg/day (females) based on no carcinogenic or other adverse effects at 
any dose level.
    A 24-month chronic/feeding oncogenicity study with rats fed dosage 
levels of 0, 89, 362 and 940 mg/kg/day (males) and 0, 113, 457 and 
1,183 mg/kg/day (females) with a systemic NOEL of 362 mg/kg/day based 
on body weight

[[Page 8643]]

effects in the female and eye effects in males. There was no 
carcinogenic response at any dose level.
    6. Carcinogenicity. A mouse oncogenicity study with mice fed dosage 
levels of 0, 150, 750 and 4,500 mg/kg/day with a NOEL of 750 mg/kg/day 
based on body weight effects and microscopic liver changes at the high 
dose. There was no carcinogenic effect at the highest dose tested of 
4,500 mg/kg/day.
    Glyphosate is classified as a Group E (evidence of non-
carcinogenicity for humans), based upon lack of convincing 
carcinogenicity evidence in adequate studies in two animal species. 
This classification is based on the following findings: (1) There were 
no tumor findings in the chronic testing that were determined to be 
compound related; (2) glyphosate was tested up to the limit dose on the 
rat and up to levels higher than the limit dose in mice; and (3) there 
is no evidence of genotoxicity for glyphosate.
    7. Animal metabolism. The nature of the residue in animals is 
adequately understood and consists of the parent, glyphosate and its 
metabolite AMPA (aminomethyl-phosphonic acid).
    8. Metabolite toxicology. Only glyphosate parent is to be regulated 
in plant and animal commodities since the metabolite AMPA is not of 
toxicological concern in food.
    9. Endocrine disruption. The toxicity studies required by EPA for 
the registration of pesticides measure numerous endpoints with 
sufficient sensitivity to detect potential endocrine-modulating 
activity. No effects have been identified in subchronic, chronic or 
developmental toxicity studies to indicate any endocrine-modulating 
activity by glyphosate. In addition, negative results were obtained 
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. More importantly, the multi-generation reproduction study in 
rodents is a complex study design which measures a broad range of 
endpoints in the reproductive system and in developing offspring that 
are sensitive to alterations by chemical agents. Glyphosate has been 
tested in two separate multi-generation studies and each time the 
results demonstrated that glyphosate is not a reproductive toxin.

C. Aggregate Exposure

    1. Dietary exposure  -- Food. For purposes of assessing the 
potential exposure under these tolerances, dietary exposure was 
estimated based on the Theoretical Maximum Residue Contribution (TMRC) 
from the all present tolerances for glyphosate and the additional 
exposure that could result if the proposed tolerances are established 
on barley grain at 20 ppm, barley bran and pearled barley at 60 ppm, 
canola seed at 10 ppm, canola meal at 25 ppm, legume vegetables 
(succulent or dried) group (except soybeans) at 5 ppm, sugar beet roots 
at 10 ppm, sugar beet tops at 10 ppm and sugar beet dried pulp at 25 
ppm. The TMRC is obtained by multiplying the tolerance level residue 
for each food commodity by the consumption data which estimates the 
amount of those products eaten by various population subgroups. In 
conducting this exposure assessment, very conservative assumptions were 
made -- 100% of these crops will contain glyphosate residues and those 
residues would be at the level of the tolerance -- which result in an 
overestimate of human exposure. Thus, in making a safety determination 
for these tolerances, EPA is taking into account this conservative 
exposure assessment.
    Secondary residues in animal commodities may occur from these uses 
through the feeding of barley grain and canola meal to livestock. Since 
these proposed tolerances do not arise from changes in U.S. 
registrations involving the use of glyphosate herbicides on barley, 
canola, or legume vegetables, it has been concluded that livestock feed 
items derived from these crops are not likely to enter channels of 
trade in the United States. Based on these considerations and the 
results of animal feeding studies and the amount of glyphosate residues 
expected in animal feeds, EPA has concluded that there is no reasonable 
expectation that such secondary residues of glyphosate will exceed 
existing tolerances in edible animal products.
    2. Drinking water. In examining aggregate exposure, FQPA directs 
EPA to consider available information concerning exposures from the 
pesticide residue via drinking water. The lifetime health advisory and 
maximum contaminant level (MCL), for glyphosate are both 700 parts per 
billion in the EPA Office of Drinking Water`s ``Drinking Water Health 
Advisory; Pesticides.'' The MCL represents the level at which no known 
or anticipated adverse health effects will occur, allowing for an 
adequate margin of safety, and is based on the reference dose (RfD). 
Environmental Fate data for glyphosate indicate little potential for 
the chemical to migrate to drinking. Glyphosate is not highly mobile 
and not persistent in a soil or water environment. Because the Agency 
lacks sufficient water-related exposure data to complete a 
comprehensive drinking water risk assessment for many pesticides, EPA 
has commenced and nearly completed a process to identify a reasonable 
yet conservative bounding figure for the potential contribution of 
water related exposures to the aggregate risk posed by a pesticide. In 
developing the bounding figure, EPA estimated residue levels in water 
for a number of specific pesticides using various data sources. The 
Agency then applied the estimated residue levels, in conjunction with 
appropriate toxicological endpoints (RfDs or acute dietary NOELs) and 
assumptions about body weight and consumption, to calculate, for each 
pesticide, the increment of aggregate risk contributed by consumption 
of contaminated water. While EPA has not yet pinpointed the appropriate 
bounding figure for consumption of contaminated water, the ranges the 
Agency is continuing to examine are all below the level that would 
cause glyphosate to exceed the RfD if the tolerances being considered 
in this document were granted. The Agency has therefore concluded that 
the potential exposures associated with glyphosate in water, even at 
higher levels the Agency may consider a conservative upper bound, would 
not prevent the Agency from determining that there is a reasonable 
certainty of no harm if the tolerance is granted.
    3. Non-dietary exposure. Glyphosate is registered for use on non-
food sites such as around ornamental, shade trees, shrubs, walks, 
driveways, flowerbeds, home lawns, farmsteads including building 
foundations, along and in fences, in dry ditches and canals, along 
ditchbanks, farm roads, shelterbelts, forestry, Christmas trees, and 
industrial sites and other non-crop or industrial areas such as 
airports, lumber yards, manufacturing sites, utility substations, 
parking areas, petroleum tank farms, and pumping station.
    Margins of Exposure (MOEs) are determined for non-dietary exposure 
based on toxicological endpoints and measured or estimated exposures. 
Since glyphosate is a class E chemical (evidence of non-carcinogenicity 
for humans), the 21 day dermal study lacked any observable effects at 
the limit dose, and no adverse effects were observed in developmental 
toxicity studies in rats up to 1,000 mg/kg/day and rabbits up to 175 
mg/kg/day, no toxicological endpoints are applicable. Because available 
data indicated no evidence of significant toxicity via the dermal or 
inhalations routes, MOEs were not calculated and risk

[[Page 8644]]

assessments are not required for non-occupational (residential uses).

D. Cumulative Effects

    EPA does not have, at this time, available data to determine 
whether glyphosate has a common mechanism of toxicity with other 
substances or how to include it in a cumulative risk assessment. Unlike 
other pesticides for which EPA has followed a cumulative risk approach 
based on common mechanism of toxicity, glyphosate does not produce a 
toxic metabolite which is common to other substances. For the purposes 
of this tolerance action, therefore EPA has assumed that glyphosate 
does not have a common mechanism of toxicity with other substances. A 
condition of the registrations associated with these tolerances will be 
that the registrant will provide common mechanism data in a timely 
manner when and if the Agency asks for it. After EPA develops 
methodologies for more fully applying common mechanism of toxicity 
issues to risk assessments, the Agency will develop a process to 
reexamine those tolerance decisions made earlier.

E. Safety Determination

    1. U.S. population --i. Acute dietary exposure. Based on the 
available acute toxicity data, glyphosate does not pose any acute 
dietary risks, and an acute dietary risk assessment is not required.
    ii. Chronic dietary exposure. Using the TAS Exposure 1 software and 
1977-78 consumption data, a chronic dietary exposure estimate was based 
on 100% of the crops treated and all residues at tolerance levels to 
provide the TMRC. Based this assessment the combined new proposed 
tolerances contribute dietary exposure equal to 0.36% of the RfD for 
U.S. population and 0.69% of the RfD for non- nursing infants under 1 
year old. Total estimated dietary exposure from glyphosate residues in 
food, taking into account both existing and these proposed uses will be 
1.4% of the RfD for the overall U.S. population and 3.1% of the RfD for 
non- nursing infants, the most highly exposed population subgroup. An 
additional risk assessment for residential uses was not required 
because of no evidence of significant toxicology via dermal or 
inhalation routes. Even though an appropriate bounding figure for 
consumption of contaminated water has not been determined, the ranges 
being examine are all below the level that would cause glyphosate to 
exceed the RfD. Generally there is no concern for exposures below 100 
percent of the RfD. Therefore, based on the completeness and 
reliability of the toxicity data and the conservative exposure 
assessment, there is reasonable certainty that no harm will occur from 
aggregate exposure to glyphosate.
    2. Infants and children. FFCDA section 408 provides that an 
additional tenfold margin of exposure (safety) for infants and children 
in the case of threshold effects to account for pre- and post-natal 
toxicity and the completeness of the database unless it is determined 
that a different margin of exposure (safety) will be safe for infants 
and children. Monsanto believes that reliable data support using the 
standard margin of exposure (usually 100 x  for combined inter- and 
intra-species variability) without the additional tenfold margin of 
exposure when a complete data base under existing guidelines exists and 
when the nature of the findings from these studies do not raise 
concerns regarding the adequacy of the standard margin of exposure.
    The toxicological database for evaluating pre- and post-natal 
toxicity for glyphosate is considered to be complete at this time. Risk 
to infants and children for glyphosate was determined by the use of two 
developmental toxicity studies in rats and rabbits and a two-generation 
reproduction study in rats. The developmental toxicity studies 
evaluates the potential for adverse effects on the developing organism 
resulting from exposure during prenatal development. The reproduction 
study provides information relating to effects from exposure to the 
chemical on the reproductive capability of both (mating) parents and on 
systemic toxicity, in addition to information on prenatal development. 
The results of these studies indicate that glyphosate does not produce 
birth defects and is not a reproductive toxin.
    In the rabbits, no developmental toxicity was observed at the 
highest dose tested (HDT) where significant maternal toxicity occurred 
(death and clinical signs at 350 mg/kg/day, highest dose tested HDT). 
Because no developmental toxicity was observed at any dose level, the 
developmental NOEL is considered to be 350 mg/kg/day. In the rat 
developmental toxicity study, severe maternal (systemic) and 
developmental toxicity was noted at 3,500 mg/kg/ day HDT. The HDT in 
this study was 3.5 times higher than the limit dose that is currently 
required by the guidelines. The maternal and developmental (pup) NOEL 
was 1,000 mg/kg/day. No effects on reproductive parameters were 
observed.
    In the rat 2-generation reproduction study, parental toxicity was 
observed at 1,500 mg/kg/day as soft stools, decreased food consumption 
and body weight gain; therefore, the systemic NOEL is considered to be 
500 mg/kg/day. Developmental (pup) toxicity was also only exhibited at 
1,500 mg/kg/day as decreased body weight gain of the F1a, 
F2a, and F2b male and female pups during the 
second and third weeks of lactation. Glyphosate did not affect the 
ability of rats to mate, conceive, carry or deliver normal offspring at 
any dose level.
    The RfD is based on the NOEL for maternal toxicity in the rabbit 
developmental study. No developmental effects were noted in the study. 
In the rat developmental study, effects were noted only at doses 20-
fold higher than the NOEL used for the RfD. No pre- or post-natal 
effects were seen in any study in the absence of maternal toxicity. In 
the rat reproduction study, developmental effects were noted at doses 5 
times higher than the NOEL used for the RfD. The Agency does not 
believe the effects seen in these studies are of such concern to 
require an additional safety factor. Accordingly, the Agency believes 
the RfD has an adequate margin of protection for infants and children. 
The dietary exposure from current and proposed uses of glyphosate 
ranges from 1% of the RfD for nursing infants (less than 1 year old) to 
3% for non-nursing infants and children 1 to 6 years old. Monsanto has 
concluded that there is reasonable certainty that no harm will occur to 
infants and children from aggregate exposure to glyphosate.

F. International Tolerances

    Codex MRLs have been established for residues of glyphosate in or 
on Barley Grain at 20 ppm, Dry Peas at 5 ppm, Dry Beans at 2 ppm, and 
Rape (Canola) Seed at 10 ppm. The proposed tolerances will achieve 
harmonization with these existing MRLs. The increase in U.S. tolerances 
on legume vegetables up to 5 ppm was recommended in 1993 in the 
glyphosate Reregistration Eligibility Decision.
    The proposed U. S. tolerances are also consistent with the MRLs 
presently established for these commodities by other trade partner 
countries such as Canada, the European Union, and Japan.

[FR Doc. 98-4187 Filed 2-19-98; 8:45 am]
BILLING CODE 6560-50-F