Document ID: EPA-HQ-OPP-2006-0023-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-06-07T04:00Z

Sodium Chlorite; Notice of Filing a Pesticide Petition to Establish a
Tolerance for a Certain Pesticide Chemical in or on Food   

Summary of Petition

    The petitioner summary of the pesticide petition is printed below as
required by FFDCA section 408(d)(3). The summary of the petition was
prepared by the petitioner and represents the view of the petitioner.
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.

Bi-oxide Crop Science LLC 

PP __ _____

    EPA has received a pesticide petition (__ ____) from Bi-oxide Crop
Science LLC, 401 South Wall Street, Suite 103, Calhoun, Georgia 30703 
proposing, pursuant to section 408(d) of the Federal Food, Drug, and
Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180 by
establishing an exemption from the requirement of a tolerance for
residues of sodium chlorite/chlorine dioxide in or on the raw
agricultural commodities wheat, barely, oats, grain, straw, and
aspirated grain fractions (wheat). Bi-oxide Crop Science LLC is seeking
to obtain a Formulator’s Exemption of Vulcan Chemical Technical Sodium
Chlorite Solution 31.25 (25% active ingredient chlorite) EPA Reg. No.
5382-43 and in doing so will expand the use of sodium chlorite on field
crops.  Consequently Bi-oxide Crop Science LLC relies on Vulcan Chemical
for supporting data. Vulcan Chemical is a member of the Chlorine Dioxide
Panel of the Chemical Manufacturers Association (CMA) of Arlington, VA. 
EPA has determined that the petition contains data or information
regarding the elements set forth in section 408(d)(2) of the FFDCA;
however, EPA has not fully evaluated the sufficiency of the submitted
data at this time or whether the data supports granting of the petition.
Additional data may be needed before EPA rules on the petition.

A. Residue Chemistry

    1. Plant metabolism. The metabolism of sodium chlorite and chlorine
dioxide in plants is adequately understood for the purposes of
establishing an exemption from the requirement of a tolerance.  Sodium
chlorite will convert to chlorine dioxide under acidic conditions.  
Chlorine dioxide is a powerful oxidizing agent that will oxidize phenol,
amine, and organosulfur groups and in turn will be reduced to the
terminal residue, chloride.  

    2. Analytical method. Chlorite residues can be determined by using
ion chromatography with a sodium borate/gluconate mobile phase and a UV
detector as described by Tsai et al. (J Food Science, 2001, 66:472-477).
The method cannot discriminate between chlorite and chlorate and the
limit of detection is 0.1ppm based on a signal-to-noise ratio of 3.

    3. Magnitude of residues. Bi-oxide Crop Science LLC requests a data
waiver for plant magnitude of residues.  This request is based on the
chemistry of sodium chlorite and chlorine dioxide.  Both of these
molecules are oxidizing agents.  Chlorine dioxide is a reactive gas that
when in contact with organic reducing agents such as phenol, amine, and
organosulfur functional groups will be reduced to chloride. When
chlorite is acidified, it is converted to chlorine dioxide and then
consequently be reduced to chloride.

B. Toxicological Profile

1. Acute toxicity.  The Bi-oxide Crop Sciences LLC 25% sodium chlorite
solution will rely on data developed by Vulcan Chemical for the 80%
technical sodium chlorite.  The oral LD50 values range from 255 to 270
mg/kg from male and female rats.  The acute dermal toxicity LD50 values
range from 129 to 140 for male and female rates.  Primary dermal
toxicity found severe necrosis that persisted for up to 14 days after
dosage for 4 out of 6 test animals.  Primary eye irritation and dermal
irritation were waived due to product corrosivity. 

2. Genotoxicity.  Bi-oxide Crop Science LLC has not generated new
mutagenicity studies in support of sodium chlorite but instead is
relying on those studies that support the Vulcan product.  EPA, in the
Integrated Risk Assessment System (IRIS) for chlorite (sodium salt)
(CASRN 7758-19-2), assessed the genotoxicity of sodium chlorite.  The
following was listed in IRIS.  Chlorite was assessed for genotoxicity in
a number of in vitro and in vivo assays.  Chlorite induced reverse
mutations in Salmonella typhimurium (with activation) and chromosome
aberrations in Chinese hamster fibroblast (Ishidate et al., 1984, Food
Chem Toxicol. 22:623-636).  In general the in vivo results were
negative.  In a micronucleus assay, negative results were found in ddY
mice following an oral gavage (Hayashi et al., 1988, Food Chem. Toxicol.
26:487-500) and in Swiss CD-1 mice as treated by gavage for 5 days at 0,
8, 20, or 40 mg/kg/day (Meier et al., 1995. Environ. Mutagen 7:201-211).
 Meier also reported negative results in the sperm head abnormality
assay in B6CC3F1 mice and in the bone marrow chromosomal aberration
assay in Swiss CD-1 mice.  Positive results were reported for a
micronucleus assay of ddY mice when chlorite was administered by
intraperitoneal injection (Hayashi, 1988).

3. Reproductive and developmental neurotoxicity. The Chlorine Dioxide
Panel produced a rat two generation reproduction and development
neurotoxicity report as was reported by Gill et al.( J. Appl. Toxicol.
2000, 20:291-303). F0 and F1 rats were allowed free access to drinking
water containing 0, 35, 70, or 300 ppm sodium chlorite for a 10-week
prebreed period, for males and through mating, gestation, and lactation
for females. The drinking water concentrations were approximately 4, 8,
and 30 mg/kg/day for males and 5, 10, and 39 mg/kg/day for females. The
intake of sodium chlorite resulted in a decrease in water consumption in
all groups and a decrease in food consumption and body weights in the 70
and 300 ppm groups.  There was no evidence of reproductive toxicity. 
Pup body weight decreased in the 300 ppm group.  Changes in the nervous
system were limited to small decrease in the auditory startle response
in pups in the 70 and 300 ppm groups and there was a small decrease in
absolute brain weight in pups the 300 ppm group.  The no-observed-effect
level (NOEL) for effects on reproduction and thyroid hormones was 300
ppm.  The no-observed-adverse-level (NOAEL) for neurotoxicity was 300
ppm.  Development toxicity of sodium chlorite in rabbit was reported by
Harrington et al. (J. Am. Coll. Toxicol. 1995, 14:108-118).  Mated New
Zealand female rabbits received 0, 200, 600, or 1,200 ppm sodium
chlorite in drinking water from day 7 to day 19 of pregnancy.  Maternal
food and water consumption decreased at 600 and 1,200 ppm, there were no
treatment-related maternal abnormalities.  There were no treatment
related fetal structural abnormalities.  The maternal and fetal NOEL was
200 ppm.  Sodium chlorite is not considered to be a teratogenic or a
selective development toxicant.

	4. Subchronic toxicity. A 13-week rat feeding study was reported by
Harrington et al. (J. Am. Coll. Toxicology. 1995, 14:21-33).  Rats were
daily gavaged with doses of sodium chlorite at 0, 10, or 80 mg/kg/day. 
At the 80 mg/kg/day dose there were several treatment-related deaths and
morphological changes in the blood chemistry.  Mean erythrocyte counts
were decreased in both sexes.  Splenic extramedullary hemopoiesis was
observed in some animals at the 80 mg/kg/day dose.  At the 25 mg/kg/day
dose methemoglobin was increased in males.  No adverse toxicological
effects (NOAEL) were observed at the 10 mg/kg/day dose.  

	5. Chronic toxicity. The EPA Integrated Risk Information System (IRIS)
reviewed the chronic toxicity of sodium chlorite.  The review (EPA,
1986) stated that chlorite is classified as Group D; not classifiable as
to human carcinogenicity.  Under the draft Carcinogen Assessment
Guidelines (EPA, 1996), the human carcinogenicity of chlorite cannot be
determined because of a lack of human data and limitations in animals
studies.  Kurokawa et al. (Environ. Health Perspect, 1986, 69:221-235)
conducted chronic oral studies with rats and found no evidence of
carcinogenic activity from chlorite.  Kurokawa’s study has limited use
since it involved an 85 week exposure period and the test animals had a
high incidence of Sendai viral infection.  Mouse studies by Kurokawa et
al. and Yokose et al. (Environ Health Perspect, 1987, 76:205-210) showed
an increase in liver and lung tumors in treated male mice; however the
short exposure duration and high incidence of early mortality in the
concurrent males from excessive fighting made statistical comparisons
between concurrent controls and treated animals difficult to interpret. 
No increases in tumor incidence were seen in female mice.  Chlorite
induced skin tumors following initiation by DMBA, but the increase was
not statistically significant.  Chlorite has shown both positive and
negative results in in vitro and in vivo genotoxicity studies.

	6. Animal metabolism. The nature of chlorine dioxide and sodium
chlorite residue in animals is adequately understood. Chlorine dioxide
is rapidly reduced to form chloride.  Sodium chlorite, while under
acidic conditions in the digestive tract will convert to chlorine
dioxide, which in turn will be reduced to chloride.  Chloride will be
eliminated by urinary routes.

	7. Metabolite toxicology. The terminal metabolite is chloride.  

	8. Endocrine disruption. Sodium chlorite and chlorine dioxide are
oxidizing agents, which in the presence of organic reducing groups will
be reduced to the terminal residue, chloride.  There were no indications
of effects on fetal developmental in either rats or rabbits. At doses
likely to be encountered from a field use of sodium chloride, is not
likely that either sodium chlorite or chlorine dioxide are endocrine
disruptors.

C. Aggregate Exposure

	1. Dietary exposure. The chronic reference dose (cRfD) and the acute
reference dose (aRfD) were determined as 0.3 mg/kg/day and 2.5
mg/kg/day, respectively.  These were based on the two generation rat
NOAEL of 30 mg/kg/day and the acute oral LD50 of 255 mg/kg/day and an
uncertainty factor of 100. These reference doses were calculated based
on EPA regulations concerning chlorite residue in drinking water since
chlorine dioxide is used in water treatment for sanitation purposes. 

    i. Food. No residue of chlorite is expected in or on wheat, barley
or oat raw agricultural commodities following the labeled use pattern
and following standard agronomic practices.  Chlorite is expected to
convert to chlorine dioxide, which in turn will be reduced to the
terminal residue, chloride. Sodium chlorite is exempt from the
requirement of a tolerance when used in growing of the raw agricultural
commodities crop group Brassica (cole) leafy vegetables and radishes (40
CFR §180.1070). EPA (Brennis, Antimicrobial Division, August 5, 2003)
approved the post-harvest use of chlorine dioxide, as generated from
sodium chlorite solution on stored potatoes at use rates of up to 400
ppm.  EPA determined that it was unlikely that there would be a residue
on the treated potatoes so no food tolerance was required.  The U.S.
Food and Drug Administration (FDA) approved the use of chlorine dioxide
on cereal flour (including wheat and barley [malted flour]) in an
unspecified quantity not more than sufficient for bleaching purposes (21
CFR §137.105).  FDA approved the used of acidified sodium chlorite for
use on poultry carcasses, red meat, sea food, and fruits and vegetables
following a potable water rinse as a secondary direct food additive (21
CFR §173.325). Sodium chlorite and chorine dioxide are also used in the
manufacturing of paper and paper board for use in contact with food (21
CFR §186.1750).

    ii. Drinking water. EPA established a maximum concentration limit
(MCL) of chlorite in drinking water of 1.0 mg/L or 1 ppm.  Chlorine
dioxide is used to treat municipal drinking water supplies.  The EPA
FIRST model (FQPA Index Reservoir Screening Tool) was used to determine
a conservative estimate of how much chlorite would move from a 427 acre
watershed to a 13 acre 9 ft deep pond.  The estimate considered 50% of
the applied material of a total of 0.2 lb ai/acre as being in the
chlorite form and further considered 8% of this moving to the pond and
that all material would be in an ionic solution form and not adsorbed to
sediment.  The total calculated residue is 10 ppb of chlorite.  The
estimated amount of chlorite that would be in solution is approximately
100 times less than that of the established MCL.  

    2. Non-dietary exposure. Sodium chlorite and chlorine dioxide are
currently not registered for use on any residential non-food site.
Therefore, residential exposure to sodium chlorite and chlorine dioxide
residues would be only through dietary exposure, including drinking
water.

D. Cumulative Effects

    There is no information currently available to indicate that toxic
effects produced by sodium chlorite and chlorine dioxide are cumulative
with those of any other compound.  

E. Safety Determination

    1. U.S. population. Based on the conservative exposure assumptions
described above and on the completeness of the toxicology database, it
can be concluded that total aggregate exposure from food and water to
the U.S. population and all evaluated population subgroups from sodium
chlorite from all proposed uses will be well below the chronic and acute
RfDs. EPA generally has no concerns for estimated exposures below 100%
of the RfD, since the RfD represents the level at or below which daily
aggregate exposure will not pose an appreciable risk to human health.
Thus, Bi-oxide Crop Sciences LLC believes it can be concluded that there
is reasonable certainty that no harm will result from aggregate exposure
to sodium chlorite residues.

    2. Infants and children. In assessing the potential for additional
sensitivity of infants and children to residues of sodium chlorite, the
data from developmental toxicity studies in both the rat and rabbit and
a two generation reproduction study in rats have been considered. The
developmental toxicity studies evaluate potential adverse effects on the
developing animal resulting from pesticide exposure to the mother during
prenatal development. The reproduction study evaluates effects from
exposure to the pesticide on the reproductive capability of mating
animals through two generations, as well as any observed systemic
toxicity. Since none of the studies indicate the offspring to be more
sensitive and all effects were secondary to severe for maternal
toxicity, Bi-oxide Crop Sciences LLC believes that infants and children
are protected and that an additional uncertainty factor for infants and
children is not warranted.

F. International Tolerances

    No CODEX maximum residue levels (MRL's) have been established for
residues of chlorine dioxide or chlorite on any crops at this time.