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Notice of Filing a Pesticide Petition to Establish a Tolerance for a Certain Pesticide Chemical in or on Food
Note: EPA no longer updates this information, but it may be useful as a reference or resource.
[Federal Register: September 6, 2000 (Volume 65, Number 173)]
[Notices]
[Page 54015-54019]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr06se00-60]
[[Page 54015]]
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ENVIRONMENTAL PROTECTION AGENCY
[PF-969; FRL-6738-4]
Notice of Filing a Pesticide Petition to Establish a Tolerance
for a Certain Pesticide Chemical in or on Food
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice.
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SUMMARY: This notice announces the initial filing of a pesticide
petition proposing the establishment of regulations for residues of a
certain pesticide chemical in or on various food commodities.
DATES: Comments, identified by docket control number PF-969, must be
received on or before October 6, 2000.
ADDRESSES: Comments may be submitted by mail, electronically, or in
person. Please follow the detailed instructions for each method as
provided in Unit I.C. of the SUPPLEMENTARY INFORMATION. To ensure
proper receipt by EPA, it is imperative that you identify docket
control number PF-969 in the subject line on the first page of your
response.
FOR FURTHER INFORMATION CONTACT: By mail: Indira Gairola, Registration
Division (7505C), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460;
telephone number: (703) 308-6379; e-mail address:
gairola.indira@epa.gov.
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this Action Apply to Me?
You may be affected by this action if you are an agricultural
producer, food manufacturer or pesticide manufacturer. Potentially
affected categories and entities may include, but are not limited to:
------------------------------------------------------------------------
Examples of
Categories NAICS codes potentially
affected entities
------------------------------------------------------------------------
Industry 111 Crop production
112 Animal production
311 Food manufacturing
32532 Pesticide
manufacturing
------------------------------------------------------------------------
This listing is not intended to be exhaustive, but rather provides
a guide for readers regarding entities likely to be affected by this
action. Other types of entities not listed in the table could also be
affected. The North American Industrial Classification System (NAICS)
codes have been provided to assist you and others in determining
whether or not this action might apply to certain entities. If you have
questions regarding the applicability of this action to a particular
entity, consult the person listed under FOR FURTHER INFORMATION
CONTACT.
B. How Can I Get Additional Information, Including Copies of this
Document and Other Related Documents?
1. Electronically. You may obtain electronic copies of this
document, and certain other related documents that might be available
electronically, from the EPA Internet Home Page at http://www.epa.gov/.
To access this document, on the Home Page select ``Laws and
Regulations,'' ``Regulations and Proposed Rules,'' and then look up the
entry for this document under the ``Federal Register--Environmental
Documents.'' You can also go directly to the Federal Register listings
at http://www.epa.gov/fedrgstr/.
2. In person. The Agency has established an official record for
this action under docket control number PF-969. The official record
consists of the documents specifically referenced in this action, any
public comments received during an applicable comment period, and other
information related to this action, including any information claimed
as confidential business information (CBI). This official record
includes the documents that are physically located in the docket, as
well as the documents that are referenced in those documents. The
public version of the official record does not include any information
claimed as CBI. The public version of the official record, which
includes printed, paper versions of any electronic comments submitted
during an applicable comment period, is available for inspection in the
Public Information and Records Integrity Branch (PIRIB), Rm. 119,
Crystal Mall #2, 1921 Jefferson Davis Highway, Arlington, VA, from 8:30
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The
PIRIB telephone number is (703) 305-5805.
C. How and to Whom Do I Submit Comments?
You may submit comments through the mail, in person, or
electronically. To ensure proper receipt by EPA, it is imperative that
you identify docket control number PF-969 in the subject line on the
first page of your response.
1. By mail. Submit your comments to: Public Information and Records
Integrity Branch (PIRIB), Information Resources and Services Division
(7502C), Office of Pesticide Programs (OPP), Environmental Protection
Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460.
2. In person or by courier. Deliver your comments to: Public
Information and Records Integrity Branch (PIRIB), Information Resources
and Services Division (7502C), Office of Pesticide Programs (OPP),
Environmental Protection Agency, Rm. 119, Crystal Mall #2, 1921
Jefferson Davis Highway, Arlington, VA. The PIRIB is open from 8:30
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The
PIRIB telephone number is (703) 305-5805.
3. Electronically. You may submit your comments electronically by
e-mail to: opp-docket@epa.gov, or you can submit a computer disk as
described above. Do not submit any information electronically that you
consider to be CBI. Avoid the use of special characters and any form of
encryption. Electronic submissions will be accepted in Wordperfect 6.1/
8.0 or ASCII file format. All comments in electronic form must be
identified by docket control number PF-969. Electronic comments may
also be filed online at many Federal Depository Libraries.
D. How Should I Handle CBI That I Want to Submit to the Agency?
Do not submit any information electronically that you consider to
be CBI. You may claim information that you submit to EPA in response to
this document as CBI by marking any part or all of that information as
CBI. Information so marked will not be disclosed except in accordance
with procedures set forth in 40 CFR part 2. In addition to one complete
version of the comment that includes any information claimed as CBI, a
copy of the comment that does not contain the information claimed as
CBI must be submitted for inclusion in the public version of the
official record. Information not marked confidential will be included
in the public version of the official record without prior notice. If
you have any questions about CBI or the procedures for claiming CBI,
please consult the person identified under FOR FURTHER INFORMATION
CONTACT.
E. What Should I Consider as I Prepare My Comments for EPA?
You may find the following suggestions helpful for preparing your
comments:
1. Explain your views as clearly as possible.
2. Describe any assumptions that you used.
[[Page 54016]]
3. Provide copies of any technical information and/or data you used
that support your views.
4. If you estimate potential burden or costs, explain how you
arrived at the estimate that you provide.
5. Provide specific examples to illustrate your concerns.
6. Make sure to submit your comments by the deadline in this
notice.
7. To ensure proper receipt by EPA, be sure to identify the docket
control number assigned to this action in the subject line on the first
page of your response. You may also provide the name, date, and Federal
Register citation.
II. What Action is the Agency Taking?
EPA has received a pesticide petition as follows proposing the
establishment and/or amendment of regulations for residues of a certain
pesticide chemical 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 this petition contains 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 support granting of the petition. Additional data
may be needed before EPA rules on the petition.
List of Subjects
Environmental protection, Agricultural commodities, Feed additives,
Food additives, Pesticides and pests, Reporting and recordkeeping
requirements.
Dated: August 23, 2000.
Peter Caulkins, Acting
Director, Registration Division, Office of Pesticide Programs.
Summary of Petition
The petitioner summary of the pesticide petition is printed below
as required by section 408(d)(3) of the FFDCA. The summary of the
petition was prepared by the petitioner and represents the view of the
petitioner. EPA is publishing the petition summary verbatim without
editing it 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.
Eden Bioscience Corporation
PP OE6177
EPA has received a pesticide petition (PP OE6177) from Eden
Bioscience Corporation, 11816 North Creek Parkway N., Bothell WA 98011-
8205] proposing, pursuant to section 408(d) of the (FFDCA), 21 U.S.C.
346a(d), to amend 40 CFR part 180 to establish an exemption from the
requirement of a tolerance for the inert ingredient sodium thiosulfate
when used as a dechlorinator in pesticide formulations for protein
based products when applied to growing crops or to raw agricultural
commodities after harvest. 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. Due to the breakdown of sodium thiosulfate in
chlorinated water to sodium chloride, water, sulfur, and sulfate prior
to application to plants, there is no plant metabolism of the parent
compound. All of the breakdown products are considered to be plant
nutrients. Sodium thiosulfate pentahydrate (CAS 10102-17-7) is an
odorless crystalline substance with a molecular weight of 248.18. The
molecular formula is Na2 S2 O3 (Na
29.08%, O 30.36%, S 40.56%). It has a pKa of 1.6, is soluble in water
(42%; by weight at 0\O\ C) and insoluble in alcohol. The aqueous
solution is practically neutral with a pH range of 6.5-8.0. In aqueous
solution sodium thiosulfate slowly decomposes to its molecular
constituents. Sodium thiosulfate pentahydrate has a melting point of
48\O\ C when heated rapidly. It loses all its water at 100\O\ C and
decomposes at higher temperatures. When sodium thiosulfate is used to
remove chlorine from an aqueous solution it follows the equations:
Na2 S2 O3 + 4Cl2 +
5H2 O = 2NaHSO4 + 8HCl and
Na2 S2 O3 + 2HCl = 2NaCl +
H2 O + S + SO2 .
2. Analytical method. Analysis of sodium thiosulfate can be
accomplished through a variety of methods. Some researchers have
employed a gas chromatographic (GC) analytical method using a C18
column and 420-E fluorescence detector for determining elution of
thiosulfate in plasma and urine. Other researchers have reported using
a high performance liquid chromatographic (HPLC) method used to
determine thiosulfate plasma and urine. Medical researchers have also
described the use of a clinical nephelometer to determine sulfate and
thiosulfate concentrations in plasma and urine.
3. Magnitude of residues. Due to the breakdown of sodium
thiosulfate in water to sodium chloride, water, sulfur and sulfate,
there are no residues of sodium thiosulfate applied to the plants.
B. Toxicological Profile
Sodium thiosulfate is considered to have low toxicity and has been
safely used for over 100 years as a therapeutic agent. Medical uses of
sodium thiosulfate have been well documented since 1895. In humans it
is employed as an antidote for acute cyanide poisoning; as a
chemoprotectant against carboplatin and cisplatin induced ototoxicity;
to prevent cyanide poisoning from treatment with sodium nitroprusside,
nitrile compounds and laetrile; to reduce calcinosis; and is used
topically to treat acne and pityriasis versicolor (tinea versicolor, a
type of ringworm). Recent studies have shown that sodium thiosulfate
may be effective in reducing some chemically induced cancers. In
veterinary medicine it is used: to treat or prevent cyanide poisoning;
as a ``general detoxifier'' to treat bloat; and when applied dermally
to treat ringworm and mange. Sodium thiosulfate is also being used
experimentally to increase food utilization in livestock.
Sodium thiosulfate is used to treat drinking water where there is
concern with high levels of chlorine, chloroform or other reactive
species, especially in drinking water produced by desalination plants.
It is also used as a dechlorinator in aquariums and aquaculture, and in
a number of manufacturing processes that require the removal of
chlorine or other reactive species.
Sodium thiosulfate is classified in the Code of Federal
Regulations, U.S. Food and Drug Administration, title 21, part 184, as
a Direct Food Substance Affirmed As Generally Recognized As Safe
(Section 184.1807) and title 21, part 582 as a Substance Generally
Recognized As Safe, (Section 582.6807). According to section 184.1807,
sodium thiosulfate is used as a formulation aid and a reducing agent.
It is used in alcoholic beverages and table salt at levels not to
exceed good manufacturing practice, currently 0.00005 percent in
alcoholic beverages and 0.1% in table salt. Section 582.6807 authorizes
the use of sodium thiosulfate as a sequestrant in salt with a tolerance
of 0.1%.
[[Page 54017]]
1. Acute toxicity. Sodium thiosulfate is not well absorbed through
the intestinal tract at high doses. Sodium thiosulfate is low in acute
toxicity but may cause irritation of the gastrointestinal tract and
purging if large quantities are ingested. Doses of 8 g/kg in rats are
reported to be non-toxic upon ingestion.
Sodium thiosulfate has been used as a topical treatment for a
variety of ailments for numerous years. Sodium thiosulfate is available
in various lotion formulations such as Komed\TM\, an acne medication
containing 8% sodium thiosulfate together with 2% salicylic acid, 25%
isopropyl alcohol and other ingredients. Tinver\TM\ and Versiclear\TM\,
are lotions used for tinea versicolor (ringworm). Both lotions contain
25% sodium thiosulfate, 1% salicylic acid and 10% isopropyl alcohol. It
is recommended that the lotions be applied twice daily to affected and
susceptible skin for at least a week to many months until complete
control of tinea versicolor is achieved. Sodium thiosulfate (12%) is
also mixed with a sterile solution of 0.5% potassium ferricyanide to
treat silver nitrate burns. No adverse effects are expected when sodium
thiosulfate is used topically.
There is little information available on inhalation toxicity of
sodium thiosulfate, but as with all dust or crystalline compounds,
breathing product dust or mist may irritate the respiratory tract.
However, sodium thiosulfate will be compressed into tablets for ease of
use, thus eliminating the hazard of dust inhalation. Product labeling
calls for mixers to wear a dust mask, thus precluding inhalation of
dust when sodium thiosulfate is present as part of the product
formulation.
The use of sodium thiosulfate as an adjuvant is not expected to
pose an inhalation hazard since it will be in tablet form or is already
incorporated into the formulation at low concentrations (one to six%).
Once the sodium thiosulfate either in tablet form or in the formulated
end product-is mixed with water, it breaks down into sodium chloride,
water, sulfur and sulfate, which eliminates further possibility of
inhalation exposure from the parent compound.
Although intravenous (IV) exposure to sodium thiosulfate is
irrelevant to concerns with its use as an adjuvant, information from IV
studies and therapeutic uses provides further data on the safety of
sodium thiosulfate.
Sodium thiosulfate is considered to be essentially a nontoxic drug,
although nausea and vomiting have been described with rapid IV
administration of antidotal doses to normal adult human volunteers. The
standard dose of sodium thiosulfate for treatment of cyanide poisoning
in humans is an IV administration of 50 mL of a 250 milligrams/mL (mg/
mL) (25%) solution. Patients also have been administered 50 mL of a 50%
sodium thiosulfate solution without adverse effects. Sodium thiosulfate
administered IV at 150-200 milligrams/kilograms (mg/kg) over a period
of 15 minutes, is part of the therapy to treat suspected cyanide
toxicity from administration of sodium nitroprusside.
The lethal dose of sodium thiosulfate when given at intravenous
doses to rats is greater than 2.5 g/kg. The IV LD50 in mice
is 1.19 g/kg, while the median lethal dose in dogs is 3 g/kg. The
lethal dose injected into the flank of rabbits was estimated to be 4 g/
kg. The main toxic effects from IV administration of sodium thiosulfate
appear to be osmotic, which result from the rapid sodium load together
with acid-base disturbances. Osmotic and acid-base disturbances have
not been observed at lower doses or from dermal or oral administration
of sodium thiosulfate.
Information from intraperitoneal (IP) studies provide further
support that sodium thiosulfate has relatively low acute toxicity.
Sodium thiosulfate protects the auditory system from the major ototoxic
effects of cisplatin and reduces other overt signs of systemic
toxicity.
Hamsters receiving IP injections of sodium thiosulfate at 1,600 mg/
kg every other day until five injections were completed showed no ill
effects from sodium thiosulfate. When sodium thiosulfate was injected
in hamsters in combination with cisplatin (a chemotherapeutic agent
that has been shown to cause ototoxicity), sodium thiosulfate provided
amelioration over a broad hearing range, as well as providing
protection from cisplatin induced gastrointestinal necrosis and
nephrotoxicity. Similarly, in a study where guinea pigs treated with
cisplatin, cisplatin and sodium thiosulfate, saline or sodium
thiosulfate only (1,600 mg/kg/day for eight days), there were no signs
of toxicity in any of the guinea pigs treated with sodium thiosulfate
only. There were no effects on body weight (bwt) or auditory brainstem
response and animals treated with cisplatin and sodium thiosulfate, had
improved hearing and lost less weight than animals treated with
cisplatin only.
Sodium thiosulfate has been shown to be an effective antidote in
mice exposed to acrylonitrile. Mice were given IP injections of sodium
thiosulfate at 400 mg/kg from 10 to 30 minutes prior to acrylonitrile
administration at the LD50 dose level of 60 mg/kg. All mice
appeared normal after prophylactic treatment with sodium thiosulfate
and showed no ill effects from subsequent acrylonitrile exposure.
Animals treated with sodium thiosulfate only, showed no evidence of
toxicity.
Aquated cisplatin has a higher uptake by tumors than that of
cisplatin, but aquated cisplatin is also more nephrotoxic. Subcutaneous
injection of sodium thiosulfate (1,000 mg/kg) five minutes before IP
administration of aquated cisplatin to B6D2F1 mice resulted in reduced
aquated cisplatin-induced nephrotoxicity.
2. Genotoxicty. Sodium thiosulfate is not genotoxic and is
regularly used in cell culture mediums as a source of sulfur. Sodium
thiosulfate does not cause cell death or reduce the rate of growth in a
wide variety of bacteria. Sodium thiosulfate is non-mutagenic to
Salmonella typhimurium and can reduce the mutagenic effects induced by
other chemicals. Sodium thiosulfate does not increase the rate of
sister chromatid exchanges (SCEs) or chromosomal aberrations in human
lymphocytes. Sodium thiosulfate has been shown to reduce the number of
SCEs in human lymphocytes and Chinese hamster (CH) lung cells when
administered simultaneously with known SCE inducers. When sodium
thiosulfate at concentrations up to 5 X 10\2\ M was added to untreated
human cells, there was no effect at all on the cells. In vitro studies
with sodium thiosulfate and LX-1 small-cell lung carcinoma cells found
that sodium thiosulfate concentrations of 10 mg/kg and above were toxic
to LX-1 cells, presumably due to high osmolarity, however, lower
concentrations of sodium thiosulfate had no effect on cell growth.
Sodium thiosulfate has also been shown to inhibit cisplatin-induced
mutagenesis in somatic tissue of Drosophila.
3. Reproductive and developmental toxicity. Sodium thiosulfate is
not considered to be a reproductive or developmental toxicant due to
its rapid breakdown in the body to normal constituents, (i.e.
thiosulfate is a normal constituent of blood and is utilized by
mitochondrial enzyme rhodanase, a.k.a. thiosulfate sulfurtransferase,
as a sulfur donor). In addition, remaining thiosulfate is rapidly
hydrolyzed by water into sodium chloride, water, sulfur and sulfate,
which are all compounds readily used by living organisms.
Use of sodium nitroprusside for the treatment of hypertensive
emergencies in pregnancy has been hampered by
[[Page 54018]]
concern for the possibility of cyanide poisoning in both the mother and
fetus. Coinfusion of sodium thiosulfate with nitroprusside in gravid
ewes prevented fetal and maternal cyanide toxicity. Physicians are
currently treating some pregnant women with IV administration of sodium
thiosulfate and sodium nitroprusside.
4. Subchronic toxicity. No studies that fall into the usual
subchronic category were found. However, data from chronic and acute
studies provides adequate information as to the non-toxicity of sodium
thiosulfate. However, it should be noted that Versiclear\TM\. Lotion
containing 25% sodium thiosulfate and 1% salicylic acid in propylene
glycol is recommended for subchronic treatment of tinea versicolor in
humans. In a series of studies of various therapeutics for cyanide
poisoning in sheep, up to 660 mg/kg of sodium thiosulfate was
administered in distilled water via stomach tube directly to the rumen
of ewes who had been treated with lethal doses of sodium cyanide (7.6
mg/kg). All ewes treated with 660 mg/kg sodium thiosulfate survived.
Ewes receiving 66.7 mg/kg sodium thiosulfate still exhibited severe
signs of cyanide poisoning and subsequently died. Based on this study,
it is recommended that cyanide toxicity in ruminants should be treated
with high doses of sodium thiosulfate (500 mg/kg or more) and repeated
as needed, since sodium thiosulfate is rapidly cleared from the body
and sustained release of free cyanide from the rumen is possible.
An evaluation of 41 potential chemopreventive agents using the
inhibition of carcinogen-induced aberrant crypt foci (ACF) in the rat
colon as the measure of efficacy found that sodium thiosulfate was one
of 18 agents that significantly reduced the incidence of ACF.
5. Chronic toxicity . Long term treatment of patients with a
variety of illness have shown that ingestion of low levels of sodium
thiosulfate is a non-toxic and safe therapeutic agent. A patient with
renal tubular acidosis 1 was treated for nine years with sodium
thiosulfate, 15-20 mmol daily (orally), to control nephrocalcinosis.
During this time period, there were no treatment-related adverse
effects, nephrocalcinosis did not worsen, and renal function improved.
Thirty four patients received daily oral doses of sodium thiosulfate
(10 mmol twice daily with p=meals) for three to four years in the
treatment of recurrent calcium urinary lithiasis. Sodium thiosulfate
was well tolerated by all patients for over four years with no apparent
toxic or side effects. It was also found that the patients only
absorbed 20-25% of the oral dose, excreting four to five mmol as
urinary thiosulfate. Higher oral dose levels of sodium thiosulfate
resulted in watery stools in some patients so was not used in this
clinical trial.
Three patients undergoing maintenance hemodialysis for more than
four years developed calcified masses. To reduce the symptoms, each
patient was given 20 mmol of sodium thiosulfate IV at the end of each
hemodialysis for the next six to 12 months. A considerable regression
of calcified masses with concurrent clinical improvement was observed
in two of the patients while the third patient showed a softening in
the mass but no regression in size due to encapsulation prior to
starting sodium thiosulfate treatment. For all patients, there were no
new calcified masses observed during sodium thiosulfate treatment,
sodium thiosulfate was well tolerated, and no apparent side effects
were observed.
6. Animal metabolism. Thiosulfate is a normal constituent of
mammalian urine. In humans, urinary thiosulfate excretion averages
approximately 30mole per 24 hours, which is less than 1% of
the total urinary sulfur load.
Sodium thiosulfate is not well absorbed when administered orally as
it is broken down in the acidic gastric juices to form sulfite and
sulphur. Research has shown that 20-25% of a chronic low level dose is
excreted in the urine as urinary thiosulfate.
When sodium thiosulfate is given intravenously, it is distributed
throughout the extracellular fluid and renal excretion occurs by
glomerular filtration and secretion. The serum half-life of thiosulfate
in humans (after bolus injections) is around 15 to 20 minutes. When
sodium thiosulfate is administered during sodium nitroprusside therapy,
the plasma half life of thiosulfate is reported to be as short as 15
minutes to as long as three hours. Depending on the dosage, around 10
to 50% of exogenous thiosulfate is eliminated unchanged via the
kidneys.
Endogenous levels of plasma and urinary thiosulfate concentrations,
determined from healthy volunteers are 1.13 0.11
milligrams/dL (mg/dL) and 0.28 0.02 mg/dL, respectively.
Clearance of endogenous thiosulfate in normal males was
0.26 0.04 mL/min, with net excretion accounting for only
0.17% of the filtered load. The majority of endogenous thiosulfate is
actively reabsorbed and endogenous levels are regulated by the kidney
through secretion into and reabsorption out of tubules.
Sodium thiosulfate is known to be a strong diuretic. Following IV
administration of sodium thiosulfate, peak thiosulfate concentrations
were obtained five minutes after injection. The half life of the
distribution phase was 23 minutes while that of the elimination phase
was 182 minutes. Urine concentration, clearance and rate of thiosulfate
excretion increased markedly after injection. Total excretion was
42.6 3.5% of the injected dose at 180 min. Total excretion
increased to only 47.4 2.4% at 18 hours after injection.
Sodium thiosulfate kinetics were also studied in patients undergoing
cancer treatment. Sodium thiosulfate was eliminated from the plasma by
first-order kinetics. On the average approximately 28% of the dose was
recovered unchanged in the urine. In these patients, 95% of the total
recoverable thiosulfate was excreted within four hours after
termination of infusion. When sodium thiosulfate is coadministered with
cisplatin (a chemotherapeutic agent that often causes nephrotoxicity),
inactive mobile metabolites of cisplatin are formed by a direct
reaction between cisplatin and sodium thiosulfate in the systemic
circulation, which results in a reduction in the amount of cisplatin in
the kidney. The strong diuretic action of sodium thiosulfate also
increases elimination of both compounds, thus minimizing the time the
remaining cisplatin is in the kidneys.
Sodium thiosulfate has been used to estimate extracellular water in
cattle and was found to reach equilibrium with extracellular water in
five to ten minutes after infusion. Sodium thiosulfate was cleared from
venous blood in a two part fashion: first, it was cleared from the
plasma into the interstitial fluid, then secondly through renal
clearance from the extracellular water. A first-order clearance of the
sodium thiosulfate was demonstrated 15 to 20 minutes after infusion.
When combined with urea, sodium thiosulfate gave reasonable estimates
of empty body water, extracellular water, intracellular water and lean
body mass. No adverse effects were noted in any of the steers.
7. Metabolite toxicology. None of the metabolites of sodium
thiosulfate are considered to be of toxicological significance.
Thiosulfate is a normal body constituent as are the other breakdown
products from the reaction of sodium thiosulfate in chlorinated water:
sodium chloride, water, sulfur and sulfate.
8. Endocrine disruption. Sodium thiosulfate does not effect the
endocrine system, except as a detoxifying agent of compounds that have
been shown to
[[Page 54019]]
adversely effect the endocrine system (i.e. chlorine and other reactant
species).
C. Aggregate Exposure
1. Dietary exposure. The proposed use of sodium thiosulfate as an
adjuvant (1 tablet to 100 gallons of water or up to 14 oz. of end
product containing 1-6% sodium thiosulfate to 100 gallons of water) to
remove chlorine and other reactive species from tank water ensures that
there is no dietary exposure to sodium thiosulfate. Due to the
breakdown of sodium thiosulfate in water to sodium chloride, water,
sulfur and sulfate, there are no residues of sodium thiosulfate applied
to the plants and thus there are no residues in food.
i. Food. The proposed use will not result in any dietary exposure
beyond what is currently present in salt and alcohol.
ii. Drinking water. There is no exposure to sodium thiosulfate
through drinking water. Any sodium thiosulfate that gets into water is
quickly broken down to the following non-toxic compounds: sodium
chloride, water, sulfur and sulfate.
2. Non-dietary exposure. The only anticipated human exposure to
non-dietary sources of sodium thiosulfate would be through medical
treatment, occupational exposure, or aquaculture (hobbyists).
D. Cumulative Effects
Studies have shown that excess sodium thiosulfate beyond endogenous
levels of thiosulfate is rapidly cleared from the body and there are no
cumulative effects. It should also be noted that with the exception of
possible occupational exposure of the mixer/loader/applicator, the
proposed uses of sodium thiosulfate will not result in exposure to any
other person or any non-target organism.
E. Safety Determination
1. U.S. population. The use of sodium thiosulfate as an adjuvant
added to tank mixes does not pose a safety concern for the U.S.
population due to the non-toxic nature of the compound and the absence
of exposure.
2. Infants and children. Infants and children will not be exposed
to sodium thiosulfate from its use as an adjuvant in conjunction with
formulated products.
F. International Tolerances
There are no known international tolerances for sodium thiosulfate.
[FR Doc. 00-22390 Filed 9-5-00; 8:45 am]
BILLING CODE 6560-50-S