[Federal Register Volume 63, Number 42 (Wednesday, March 4, 1998)]
[Notices]
[Pages 10614-10619]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-5257]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-792; FRL-5772-6]


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 food commodities.
DATES: Comments, identified by the docket control number PF-792, must 
be received on or before April 3, 1998.
ADDRESSES: By mail submit written comments to: Public Information and 
Records Integrity Branch, Information Resources and Services Division 
(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.

[[Page 10615]]

    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: The product manager listed in the 
table below:

------------------------------------------------------------------------
                                   Office location/                     
        Product Manager            telephone number          Address    
------------------------------------------------------------------------
Jim Tompkins (PM 25)..........  Rm. 239, CM #2, 703-    1921 Jefferson  
                                 305-5697, e-            Davis Hwy,     
                                 mail:tompkins.jim@epa   Arlington, VA  
                                 mail.epa.gov.                          
------------------------------------------------------------------------

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 food 
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 granting of 
the petition. Additional data may be needed before EPA rules on the 
petition.
    The official record for this notice of filing, as well as the 
public version, has been established for this notice of filing under 
docket control number [PF-792] (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 [PF-792] and appropriate petition 
number. Electronic comments on this notice may be filed online at many 
Federal Depository Libraries.

List of Subjects

    Environmental protection, Agricultural commodities, Food additives, 
Feed additives, Pesticides and pests, Reporting and recordkeeping 
requirements.

    Dated: February 12, 1998.

Donald R. Stubbs,

Acting Director, Registration Division, Office of Pesticide Programs.

Summaries of Petitions

    Petitioner summaries of the pesticide petitions are printed below 
as required by section 408(d)(3) of the FFDCA. The summaries of the 
petitions were prepared by the petitioners and represent the views of 
the petitioners. EPA is publishing the petition summaries verbatim 
without editing them in any way. 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 Zeneca Ag Products

PP OF3860

    EPA has received a pesticide petition (PP 0F3860) from Zeneca Ag 
Products, 1800 Concord Pike, P. O. Box 15458, Wilmington, DE 19850-
5458, requesting pursuant to section 408(d) of the Federal Food, Drug 
and Cosmetic Act, 21 U.S.C. 346a(d), to amend 40 CFR 180.489 by 
removing the expiration date of April 10, 1998 for residues of 
sulfosate (glyphosate-trimesium; sulfonium, trimethyl salt with N-
(phosphonomethyl)glycine (1:1)) in or on the raw agricultural 
commodities (RACs) for soybean forage (2.00 ppm, of which no more than 
1 ppm is trimethylsulfonium (TMS)), soybean aspirated grain fractions 
(210.00 ppm, of which no more than 60 ppm is TMS), soybean hay (5.00 
ppm, of which no more than 2 ppm is TMS), and soybean seed (3.00 ppm, 
of which no more than 1 ppm is TMS). 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 
support granting of the petition. Additional data may be needed before 
EPA rules on the petition.

A. Residue Chemistry

    1. Plant metabolism. The metabolism of sulfosate has been studied 
in corn, grapes, and soybeans. EPA has concluded that the nature of the 
residue is adequately understood and that the residues of concern are 
the parent ions only N-(phosphonomethyl)-glycine anion (PMG) and 
trimethylsulfonium cation (TMS).
    2. Analytical method.  Gas chromatography/mass selective detector 
methods have been developed for PMG analysis in crops, animal tissues, 
milk, and eggs. Gas chromatography detection methods have been 
developed for TMS in crops, animal tissues, milk, and eggs.
    3. Magnitude of residues-- magnitude of residues in crops--i. 
Soybeans. A total of 20 field residue trials were conducted in Regions 
2 (3 trials), 4 (4 trials), and 5 (13 trials). The first application 
was a preplant or preemergence broadcast application at a rate of 8.0 
lbs ai/A. A spot treatment was made to a 10% area of each plot 43 - 99 
days after the initial treatment. The spot application rate was 2-20 
lbs ai/A on a treated basis. Forage samples were harvested at the R3 
(early pod) stage of soybean development from each treated plot 7-14 
days after the spot application in 6 trials and prior to the spot 
application in 12 trials. A wiper application was made in all trials 
approximately 1 week prior to harvest of mature seed. Hay was collected 
at normal harvest, 7-8 weeks following the spot application in most 
trials. Seed were collected at normal harvest approximately 1 week 
after the wiper application. Analysis of the treated samples showed 
maximum residues were < 0.78 ppm in forage, 1.19 ppm in hay and 0.73 
ppm in seed for TMS; and 0.60 ppm in forage, 2.7 ppm in hay, and 1.7 
ppm in seed for PMG. These data

[[Page 10616]]

support the following tolerances for residue of sulfosate: soybean 
forage - 2.0 ppm (of which no more than 1.0 ppm is TMS); soybean hay 
5.0 ppm (of which no more than 2.0 ppm is TMS); and soybean seed 3.0 
ppm (of which no more than 1.0 ppm is TMS).
    Concentration of residues is seen in aspirated grain fractions. The 
appropriate concentration factors for aspirated grain fractions are 
73.8 (PMG) and 57.5 (TMS). The appropriate tolerance for aspirated 
grain fractions is 210 ppm (of which no more than 60 ppm is TMS).
    ii. Magnitude of residue in animals-- a. Ruminants. The maximum 
practical dietary burden in dairy cows for sulfosate results from a 
diet of soybean RAC's for a total dietary burden of 54.4 ppm. In a cow 
feeding study one of the dosing levels was 50 ppm, very close to the 
estimated ruminant dietary burden. Based on these results, the 
appropriate tolerance levels are: 0.1 ppm for cattle, goat, hog, horse, 
and sheep fat; 1 ppm for cattle, goat, hog, horse, and sheep meat by-
products; 0.2 ppm for cattle, goat, hog, horse, and sheep meat; and 0.2 
ppm in milk.
    b. Poultry. The maximum poultry dietary burden for sulfosate 
results from a diet comprised of soybean and corn RACs for a total 
dietary burden of 2.7 ppm. Comparison to a poultry feeding study at a 
dosing level of 5 ppm indicates that the appropriate tolerance levels 
would be 0.05 ppm for poultry liver, fat, and meat; 0.10 ppm for 
poultry meat by-products; and 0.02 ppm for eggs.

B. Toxicological Profile

    1.  Acute toxicity. Several acute toxicology studies have been 
conducted placing technical grade sulfosate in Toxicity Category III 
and Toxicity Category IV. The acute oral LD50 in rat for 
sulfosate technical is 750 mg/kg.
    2. Genotoxicty. Mutagenicity data includes two Ames tests with 
Salmonella typhimurium; a sex linked recessive lethal test with 
Drosophila melanoga; a forward mutation (mouse lymphoma) test; an in 
vivo bone marrow cytogenetics test in rats; a micronucleus assay in 
mice; an in vitro chromosomal aberration test in Chinese hamster ovary 
cells (CHO) (no aberrations were observed either with or without S9 
activation and there were no increases in sister chromatid exchanges); 
and a morphological transformation test in mice (all negative). A 
chronic feeding/carcinogenicity study was conducted in male and female 
rats fed dose levels of 0, 100, 500 and 1,000 ppm (0, 4.2., 21.2 or 
41.8 mg/kg/day in males and 0, 5.4, 27.0 or 55.7 mg/kg day in females). 
No carcinogenic effects were observed under the conditions of the 
study. The systemic NOEL of 1,000 ppm (41.1/55.7 mg/kg/day for males 
and females, respectively) was based on decreased body weight gains 
(considered secondary to reduced food consumption) and increased 
incidences of chronic laryngeal and nasopharyngeal inflammation 
(males). A chronic feeding/carcinogenicity study was conducted in male 
and female mice fed dosage levels of 0, 100, 1,000 and 8,000 ppm (0, 
11.7, 118 or 991 mg/kg/day in males and 0, 16, 159 or 1,341 mg/kg/day 
in females). No carcinogenic effects were observed under the conditions 
of the study at dose levels up to and including the 8,000 ppm HDT 
(highest dose may have been excessive). The systemic NOEL was 1,000 ppm 
based on decreases in body weight and feed consumption (both sexes), 
increases in the incidences of white matter degeneration in the lumbar 
spinal cord (males only), and increased incidences of duodenal 
epithelial hyperplasia (females only). Sulfosate is classified as a 
Group E carcinogen based on no evidence of carcinogenicity in rat and 
mouse studies.
    3. Reproductive and developmental toxicity. A developmental 
toxicity study in rats was conducted at doses of 0, 30, 100 and 333 mg/
kg/day. The maternal (systemic) NOEL was 100 mg/kg/day, based on 
decreased body weight gain and food consumption, and clinical signs 
(salivation, chromorhinorrhea, and lethargy) seen at 333 mg/kg/day. The 
reproductive NOEL was 100 mg/kg/day, based on decreased mean pup 
weight. The decreased pup weight is a direct result of the maternal 
toxicity. A developmental toxicity study was conducted in rabbits at 
doses of 0, 10, 40 and 100 mg/kg/day with developmental and maternal 
toxicity NOELs of 40 mg/kg/day based on the following:
    i. Maternal effects. Six of 17 dams died (2 of the 4 non-gravid 
dams); 4 of 11 dams aborted; clinical signs - higher incidence and 
earlier onset of diarrhea, anorexia, decreased body weight gain and 
food consumption.
    ii. Fetal effects. decreased litter sizes due to increased post-
implantation loss, seen at 100 mg/kg/day (HDT). The fetal effects were 
clearly a result of significant maternal toxicity. A two generation 
reproduction study in rats fed dosage rates of 0, 150, 800 and 2,000 
ppm (equivalent to calculated doses of 0, 7.5, 40, and 100 mg/kg/day 
for males and females, based on a factor of 20).
The maternal (systemic) NOEL was 150 ppm (7.5 mg/kg/day), based on 
decreases in body weight and body weight gains accompanied by decreased 
food consumption, and reduced absolute and sometimes relative organ 
(thymus, heart, kidney & liver) weights seen at 800 and 2,000 ppm (40 
and 100 mg/kg/day). The reproductive NOEL was 150 ppm (7.5 mg/kg/day), 
based on decreased mean pup weights during lactation (after day 7) in 
the second litters at 800 ppm (40 mg/kg/day) and in all litters at 
2,000 ppm (100 mg/kg/day), and decreased litter size in the F0a and F1b 
litters at 2,000 ppm (100 mg/kg/day). The statistically significant 
decreases in pup weights at the 800 ppm level were borderline 
biologically significant because at no time were either the body 
weights or body weight gains less than 90% of the control values and 
because the effect was not apparent in all litters. Both the slight 
reductions in litter size at 2,000 ppm and the reductions in pup 
weights at 800 and 2,000 ppm appear to be secondary to the health of 
the dams. There was no evidence of altered intrauterine development, 
increased stillborns, or pup anomalies. The effects are primarily a 
result of feed palatability leading to reduced food consumption and 
decreases in body weight gains in the dams.
    4. Subchronic toxicity.  Two subchronic 90-day feeding studies with 
dogs and a 1-year feeding study in dogs have been conducted. In the 1-
year study dogs were fed 0, 2, 10 or 50 mg/kg/day. The No Observable 
Effect Level (NOEL) was determined to be 10 mg/kg/day based on 
decreases in lactate dehydrogenase (LDH) at 50 mg/kg/day. In the first 
90-day study, dogs were fed dosage levels of 0, 2, 10 and 50 mg/kg/day. 
The NOEL in this study was 10 mg/kg/day based on transient salivation, 
and increased frequency and earlier onset of emesis in both sexes at 50 
mg/kg/day. A second 90-day feeding study with dogs dosed at 0, 10, 25 
and 50 mg/kg/day was conducted to refine the threshold of effects. 
There was evidence of toxicity at the top dose of 50 mg/kg/day with a 
no observed effect level of 25 mg/kg/day. Adverse effects from oral 
exposure to sulfosate occur at or above 50 mg/kg/day. These effects 
consist primarily of transient salivation, which is regarded as a 
pharmacological rather than toxicological effect, emesis and non-
biologically significant hematological changes. Exposures at or below 
25 mg/kg/day have not resulted in significant biological adverse 
effects. In addition, a comparison of data from the 90-day and 1-year 
studies indicates that there is no evidence for increased toxicity with 
time. The overall NOEL in the dog is 25 mg/kg/day.

[[Page 10617]]

    5. Chronic toxicity. A chronic feeding/carcinogenicity study was 
conducted in male and female rats fed dose levels of 0, 100, 500 and 
1,000 ppm (0, 4.2, 21.2 or 41.8 mg/kg/day in males and 0, 5.4, 27.0 or 
55.7 mg/kg day in females). No carcinogenic effects were observed under 
the conditions of the study. The systemic NOEL of 1,000 ppm (41.1/55.7 
mg/kg/day for males and females, respectively) was based on decreased 
body weight gains (considered secondary to reduced food consumption) 
and increased incidences of chronic laryngeal and nasopharyngeal 
inflammation (males). A chronic feeding/carcinogenicity study was 
conducted in male and female mice fed dosage levels of 0, 100, 1,000 
and 8,000 ppm (0, 11.7, 118 or 991 mg/kg/day in males and 0, 16, 159 or 
1,341 mg/kg/day in females). No carcinogenic effects were observed 
under the conditions of the study at dose levels up to and including 
the 8,000 ppm HDT (highest dose may have been excessive). The systemic 
NOEL was 1,000 ppm based on decreases in body weight and feed 
consumption (both sexes), increases in the incidences of white matter 
degeneration in the lumbar spinal cord (males only), and increased 
incidences of duodenal epithelial hyperplasia (females only). Sulfosate 
is classified as a Group E carcinogen based on no evidence of 
carcinogenicity in rat and mouse studies.
    6. Animal metabolism. The metabolism of sulfosate has been studied 
in animals. The residues of concern for sulfosate in meat, milk, and 
eggs are the parent ions PMG and TMS only.
    7. Metabolite toxicology. There are no metabolites of toxicological 
concern. Only the parent ions, PMG and TMS are of toxicological 
concern.

C. Aggregate Exposure

    1. Dietary (food) exposure. For the purposes of assessing the 
potential dietary exposure, Zeneca has utilized the tolerance level for 
all existing tolerances and proposed tolerances; and 100% crop treated 
acreage for all commodities. Assuming that 100% of foods, meat, eggs, 
and milk products will contain sulfosate residues and those residues 
will be at the level of the tolerance results in an overestimate of 
human exposure. This is a very conservative approach to exposure 
assessment. For all existing tolerances, all proposed tolerances, and 
the proposed maximum permissible levels proposed in this notice of 
filing, the potential exposure for the U.S. population is 0.0184 
milligrams per kilogram of bodyweight per day (mg/kg bwt/day). 
Potential exposure for children's population subgroups range from 
0.0151 mg/kg bwt/day for nursing infants (< 1 year old) to 0.0763 mg/kg 
bwt/day for non-nursing infants (< 1 year old).
    2. Drinking water. Sulfosate adsorbs fairly strongly to soil and 
would not be expected to move vertically below the 6 inch soil layer. 
The N-phosphonomethyl moiety is readily degraded by soil microbes to 
AMPA with a half-life of 48 to 72 hours. AMPA is further degraded to 
CO2. In addition, the trimethylsulfonium moiety degrades 
rapidly to CO2 with a half-life of 72 hours. Therefore, 
sulfosate would not be a contaminant of groundwater. Additionally, 
since sulfosate has no aquatic uses, residues are not expected in 
drinking water.
    3. Non-dietary exposure. Since sulfosate is not registered for 
residential or turf uses, and does not represent groundwater 
contamination concern, exposures from other than dietary or 
occupational sources are not expected to occur.

D. Cumulative Effects

     There is no information to indicate that toxic effects produced by 
sulfosate are cumulative with those of any other chemical compound.

E. Safety Determination

     The appropriate toxicity endpoint for use in determining a 
Reference Dose (RfD) is the NOEL of 25 mg/kg/day, based on the 90-day 
dog study. Adverse effects resulting from exposure to sulfosate occur 
at or above approximately 40 mg/kg/day across all species tested (rat, 
mouse, rabbit and dog). The RfD based on a 90-day dog feeding study 
(NOEL of 25 mg/kg/day) using a hundredfold safety factor is calculated 
to be 0.25 mg/kg/day.
    1. U.S. population. Using the conservative assumptions of 100% of 
all crops treated and assuming all residues are at the tolerance level 
for all established and proposed tolerances, the aggregate exposure to 
sulfosate will utilize 7.4% of the RfD for the U.S. population. 
Generally there are no concerns for exposures below 100% of the RfD.
    2. Infants and children. The database on sulfosate relative to pre- 
and post-natal toxicity is complete. Because the developmental and 
reproductive effects occurred in the presence of parental (systemic) 
toxicity, these data do not suggest an increased pre- or post-natal 
sensitivity of children and infants to sulfosate exposure. Therefore, 
Zeneca concludes, upon the basis of reliable data, that a hundredfold 
uncertainty factor is adequate to protect the safety of infants and 
children and an additional safety factor is unwarranted.
    Using the conservative assumptions of 100% of all crops treated and 
assuming all residues are at the tolerance level for all established 
and proposed tolerances described above, we conclude that the percent 
of the RfD that will be utilized by aggregate exposure to residues of 
sulfosate ranges from 6.1% for nursing infants up to 30.5% for non-
nursing infants (< 1 year old).

F. International Tolerances

    There are no Codex Maximum Residue Levels established for 
sulfosate.

2. Zeneca Ag Products

PP 9F3796

    EPA has received a pesticide petition (PP 9F3796) from Zeneca Ag 
Products, 1800 Concord Pike, P. O. Box 15458, Wilmington, DE 19850-
5458, requesting pursuant to section 408(d) of the Federal Food, Drug 
and Cosmetic Act, 21 U.S.C. 346a(d), to amend 40 CFR 180.489 by 
removing the expiration date of March 9, 1998 for residues of sulfosate 
(glyphosate-trimesium; sulfonium, trimethyl salt with N-
(phosphonomethyl)glycine (1:1)) in or on the raw agricultural 
commodities (RACs) for cattle, goat, hog, horse, sheep and poultry fat 
(0.10 ppm), meat by products (1.00 ppm), and meat (0.20 ppm); poultry 
liver (0.05 ppm), poultry meat by-products (0.10 ppm), and poultry meat 
(0.05 ppm); corn fodder (0.30, of which no more than 0.20 is 
trimethylsulfonium TMS)), corn forage (0.10 ppm), and corn grain (0.20 
ppm, of which no more than 0.10 ppm is TMS); milk (0.20 ppm); and eggs 
(0.02 ppm). 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 support granting of the 
petition. Additional data may be needed before EPA rules on the 
petition.

A. Residue Chemistry

    1. Plant metabolism. The metabolism of sulfosate has been studied 
in corn, grapes, and soybeans. EPA has concluded that the nature of the 
residue is adequately understood and that the residues of concern are 
the parent ions only N-(phosphonomethyl)-glycine anion (PMG) and 
trimethylsulfonium cation (TMS).
     2. Analytical method. Gas chromatography/mass selective detector 
methods have been developed for PMG

[[Page 10618]]

analysis in crops, animal tissues, milk, and eggs. Gas chromatography 
detection methods have been developed for TMS in crops, animal tissues, 
milk, and eggs. 
     3. Magnitude of residues--crops-- i. Corn. A total of 25 field 
residue trials were conducted in Regions 1 (2 trials), 2 (2 trials), 5 
(18 trials), 7 (1 trial), 8 (1 trial), and 10 (1 trial). The first 
application was a preemergence broadcast application at a rate of 8.0 
lbs ai/A. A spot treatment was made to a 10% area of each plot 30-57 
days after the initial treatment. The application rate was 2-20 lbs ai/
A on a treated basis. Forage samples were harvested from each treated 
plot 2-8 weeks after the second application. Fodder and grain samples 
were obtained at maturity. Analysis of the treated samples showed 
maximum residues were < 6.1 ppm in forage, 0.13 ppm in fodder and 0.06 
ppm in grain for TMS; and < 0.1 ppm in forage, < 0.1 ppm in fodder and 
0.07 ppm in grain for PMG. These data support the following tolerances 
for residue of sulfosate: corn forage - 0.10 ppm; corn fodder - 0.30 
ppm (of which no more than 0.2 ppm is TMS); and corn grain - 0.20 ppm 
(of which no more than 0.10 ppm is TMS). There is no concentration of 
residues in corn processed fractions.
    ii. Animals-- ruminants. The maximum practical dietary burden in 
dairy cows for sulfosate results from a diet of soybean RAC's for a 
total dietary burden of 54.4 ppm. In a cow feeding study one of the 
dosing levels was 50 ppm, very close to the estimated ruminant dietary 
burden. Based on these results, the appropriate tolerance levels are: 
0.1 ppm for cattle, goat, hog, horse, and sheep fat; 1 ppm for cattle, 
goat, hog, horse, and sheep meat by-products; 0.2 ppm for cattle, goat, 
hog, horse, and sheep meat; and 0.2 ppm in milk.
    iii. Poultry. The maximum poultry dietary burden for sulfosate 
results from a diet comprised of soybean and corn RACs for a total 
dietary burden of 2.7 ppm. Comparison to a poultry feeding study at a 
dosing level of 5 ppm indicates that the appropriate tolerance levels 
would be 0.05 ppm for poultry liver, fat, and meat; 0.10 ppm for 
poultry meat by-products; and 0.02 ppm for eggs.

B. Toxicological Profile

    1.  Acute toxicity. Several acute toxicology studies have been 
conducted placing technical grade sulfosate in Toxicity Category III 
and Toxicity Category IV. The acute oral LD50 in rat for 
sulfosate technical is 750 mg/kg.
    2. Genotoxicty. Mutagenicity data include two Ames tests with 
Salmonella typhimurium; a sex linked recessive lethal test with 
Drosophila melanoga; a forward mutation (mouse lymphoma) test; an in 
vivo bone marrow cytogenetics test in rats; a micronucleus assay in 
mice; an in vitro chromosomal aberration test in Chinese hamster ovary 
cells (CHO) (no aberrations were observed either with or without S9 
activation and there were no increases in sister chromatid exchanges); 
and a morphological transformation test in mice (all negative). A 
chronic feeding/carcinogenicity study was conducted in male and female 
rats fed dose levels of 0, 100, 500 and 1,000 ppm (0, 4.2., 21.2 or 
41.8 mg/kg/day in males and 0, 5.4, 27.0 or 55.7 mg/kg day in females). 
No carcinogenic effects were observed under the conditions of the 
study. The systemic NOEL of 1,000 ppm (41.1/55.7 mg/kg/day for males 
and females, respectively) was based on decreased body weight gains 
(considered secondary to reduced food consumption) and increased 
incidences of chronic laryngeal and nasopharyngeal inflammation 
(males). A chronic feeding/carcinogenicity study was conducted in male 
and female mice fed dosage levels of 0, 100, 1,000 and 8,000 ppm (0, 
11.7, 118 or 991 mg/kg/day in males and 0, 16, 159 or 1,341 mg/kg/day 
in females). No carcinogenic effects were observed under the conditions 
of the study at dose levels up to and including the 8,000 ppm HDT 
(highest dose may have been excessive). The systemic NOEL was 1,000 ppm 
based on decreases in body weight and feed consumption (both sexes), 
increases in the incidences of white matter degeneration in the lumbar 
spinal cord (males only), and increased incidences of duodenal 
epithelial hyperplasia (females only). Sulfosate is classified as a 
Group E carcinogen based on no evidence of carcinogenicity in rat and 
mouse studies.
    3. Reproductive and developmental toxicity. A developmental 
toxicity study in rats was conducted at doses of 0, 30, 100 and 333 mg/
kg/day. The maternal (systemic) NOEL was 100 mg/kg/day, based on 
decreased body weight gain and food consumption, and clinical signs 
(salivation, chromorhinorrhea, and lethargy) seen at 333 mg/kg/day. The 
reproductive NOEL was 100 mg/kg/day, based on decreased mean pup 
weight. The decreased pup weight is a direct result of the maternal 
toxicity. A developmental toxicity study was conducted in rabbits at 
doses of 0, 10, 40 and 100 mg/kg/day with developmental and maternal 
toxicity NOELs of 40 mg/kg/day based on the following:
    i. Maternal effects. Six of 17 dams died (2 of the 4 non-gravid 
dams); 4 of 11 dams aborted; clinical signs - higher incidence and 
earlier onset of diarrhea, anorexia, decreased body weight gain and 
food consumption.
    ii. Fetal effects. Decreased litter sizes due to increased post-
implantation loss, seen at 100 mg/kg/day (HDT). The fetal effects were 
clearly a result of significant maternal toxicity. A two generation 
reproduction study in rats fed dosage rates of 0, 150, 800 and 2,000 
ppm (equivalent to calculated doses of 0, 7.5, 40, and 100 mg/kg/day 
for males and females, based on a factor of 20).
The maternal (systemic) NOEL was 150 ppm (7.5 mg/kg/day), based on 
decreases in body weight and body weight gains accompanied by decreased 
food consumption, and reduced absolute and sometimes relative organ 
(thymus, heart, kidney & liver) weights seen at 800 and 2,000 ppm (40 
and 100 mg/kg/day). The reproductive NOEL was 150 ppm (7.5 mg/kg/day), 
based on decreased mean pup weights during lactation (after day 7) in 
the second litters at 800 ppm (40 mg/kg/day) and in all litters at 
2,000 ppm (100 mg/kg/day), and decreased litter size in the F0a and F1b 
litters at 2,000 ppm (100 mg/kg/day). The statistically significant 
decreases in pup weights at the 800 ppm level were borderline 
biologically significant because at no time were either the body 
weights or body weight gains less than 90% of the control values and 
because the effect was not apparent in all litters. Both the slight 
reductions in litter size at 2,000 ppm and the reductions in pup 
weights at 800 and 2,000 ppm appear to be secondary to the health of 
the dams. There was no evidence of altered intrauterine development, 
increased stillborns, or pup anomalies. The effects are primarily a 
result of feed palatability leading to reduced food consumption and 
decreases in body weight gains in the dams.
    4. Subchronic toxicity. Two subchronic 90-day feeding studies with 
dogs and a 1-year feeding study in dogs have been conducted. In the 1-
year study dogs were fed 0, 2, 10 or 50 mg/kg/day. The No Observable 
Effect Level (NOEL) was determined to be 10 mg/kg/day based on 
decreases in lactate dehydrogenase (LDH) at 50 mg/kg/day. In the first 
90-day study, dogs were fed dosage levels of 0, 2, 10 and 50 mg/kg/day. 
The NOEL in this study was 10 mg/kg/day based on transient salivation, 
and increased frequency and earlier onset of emesis in both sexes at 50 
mg/kg/day. A second 90-day feeding study with dogs dosed at 0, 10, 25 
and 50 mg/kg/day was conducted to refine the

[[Page 10619]]

threshold of effects. There was evidence of toxicity at the top dose of 
50 mg/kg/day with a no observed effect level of 25 mg/kg/day. Adverse 
effects from oral exposure to sulfosate occur at or above 50 mg/kg/day. 
These effects consist primarily of transient salivation, which is 
regarded as a pharmacological rather than toxicological effect, emesis 
and non-biologically significant hematological changes. Exposures at or 
below 25 mg/kg/day have not resulted in significant biological adverse 
effects. In addition, a comparison of data from the 90 day and 1 year 
studies indicates that there is no evidence for increased toxicity with 
time. The overall NOEL in the dog is 25 mg/kg/day.
    5. Chronic toxicity. A chronic feeding/carcinogenicity study was 
conducted in male and female rats fed dose levels of 0, 100, 500 and 
1,000 ppm (0, 4.2., 21.2 or 41.8 mg/kg/day in males and 0, 5.4, 27.0 or 
55.7 mg/kg day in females). No carcinogenic effects were observed under 
the conditions of the study. The systemic NOEL of 1,000 ppm (41.1/55.7 
mg/kg/day for males and females, respectively) was based on decreased 
body weight gains (considered secondary to reduced food consumption) 
and increased incidences of chronic laryngeal and nasopharyngeal 
inflammation (males). A chronic feeding/carcinogenicity study was 
conducted in male and female mice fed dosage levels of 0, 100, 1,000 
and 8,000 ppm (0, 11.7, 118 or 991 mg/kg/day in males and 0, 16, 159 or 
1,341 mg/kg/day in females). No carcinogenic effects were observed 
under the conditions of the study at dose levels up to and including 
the 8,000 ppm HDT (highest dose may have been excessive). The systemic 
NOEL was 1,000 ppm based on decreases in body weight and feed 
consumption (both sexes), increases in the incidences of white matter 
degeneration in the lumbar spinal cord (males only), and increased 
incidences of duodenal epithelial hyperplasia (females only). Sulfosate 
is classified as a Group E carcinogen based on no evidence of 
carcinogenicity in rat and mouse studies.
     6.  Animal metabolism. The metabolism of sulfosate has been 
studied in animals. The residues of concern for sulfosate in meat, 
milk, and eggs are the parent ions PMG and TMS only.
    7. Metabolite toxicology. There are no metabolites of toxicological 
concern. Only the parent ions, PMG and TMS are of toxicological 
concern.

C. Aggregate Exposure

    1. Dietary (food) exposure. For the purposes of assessing the 
potential dietary exposure, Zeneca has utilized the tolerance level for 
all existing tolerances, and proposed Tolerances; and 100% crop treated 
acreage for all commodities. Assuming that 100% of foods, meat, eggs, 
and milk products will contain sulfosate residues and those residues 
will be at the level of the tolerance results in an overestimate of 
human exposure. This is a very conservative approach to exposure 
assessment. For all existing tolerances and the proposed maximum 
permissible levels proposed in this notice of filing, the potential 
exposure for the U.S. population is 0.0184 mg/kg bwt/day. Potential 
exposure for children's population subgroups range from 0.0151 mg/kg 
bwt/day for nursing infants ( < 1 year old) to 0.0763 mg/kg bwt/day for 
non-nursing infants (> 1 year old).
    2. Drinking water. Sulfosate adsorbs fairly strongly to soil and 
would not be expected to move vertically below the 6 inch soil layer. 
The N-phosphonomethyl moiety is readily degraded by soil microbes to 
AMPA with a half-life of 48 to 72 hours. AMPA is further degraded to 
CO2. In addition, the trimethylsulfonium moiety degrades 
rapidly to CO2 with a half-life of 72 hours. Therefore, 
sulfosate would not be a contaminant of groundwater. Additionally, 
since sulfosate has no aquatic uses, residues are not expected in 
drinking water.
    3. Non-dietary exposure. Since sulfosate is not registered for 
residential or turf uses, and does not represent groundwater 
contamination concern, exposures from other than dietary or 
occupational sources are not expected to occur.

D. Cumulative Effects

     There is no information to indicate that toxic effects produced by 
sulfosate are cumulative with those of any other chemical compound.

E. Safety Determination

     The appropriate toxicity endpoint for use in determining a 
Reference Dose (RfD) is the NOEL of 25 mg/kg/day, based on the 90-day 
dog study. Adverse effects resulting from exposure to sulfosate occur 
at or above approximately 40 mg/kg/day across all species tested (rat, 
mouse, rabbit and dog). The RfD based on a 90-day dog feeding study 
(NOEL of 25 mg/kg/day) using a hundredfold safety factor is calculated 
to be 0.25 mg/kg/day.
    1. U.S. population. Using the conservative assumptions of 100% of 
all crops treated and assuming all residues are at the tolerance level 
for all established and proposed tolerances, the aggregate exposure to 
sulfosate will utilize 7.4% of the RfD for the US population. Generally 
there are no concerns for exposures below 100 percent of the RfD.
    2. Infants and children. The database on sulfosate relative to pre- 
and post-natal toxicity is complete. Because the developmental and 
reproductive effects occurred in the presence of parental (systemic) 
toxicity, these data do not suggest an increased pre- or post-natal 
sensitivity of children and infants to sulfosate exposure. Therefore, 
Zeneca concludes, upon the basis of reliable data, that a hundredfold 
uncertainty factor is adequate to protect the safety of infants and 
children and an additional safety factor is unwarranted. Using the 
conservative assumptions of 100% of all crops treated and assuming all 
residues are at the tolerance level for all established and proposed 
tolerances described above, we conclude that the percent of the RfD 
that will be utilized by aggregate exposure to residues of sulfosate 
ranges from 6.1% for nursing infants up to 30.5% for non-nursing 
infants (< 1 year old).

 F. International Tolerances.

    There are no Codex Maximum Residue Levels established for 
sulfosate.

[FR Doc. 98-5257 Filed 3-3-98; 8:45 am]
BILLING CODE 6560-50-F