[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:
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Office location/
Product Manager telephone number Address
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Jim Tompkins (PM 25).......... Rm. 239, CM #2, 703- 1921 Jefferson
305-5697, e- Davis Hwy,
mail:[email protected] Arlington, VA
mail.epa.gov.
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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:
opp-docket@epamail.epa.gov
Electronic comments must be submitted as an ASCII file avoiding the
use of special characters and any form of encryption. 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="">50 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="">2. 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="">50 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="">