v=/EPA
United States Prevention, Pesticides EPA 738-R-05-004
Environmental Protection and Toxic Substances June 2005
Agency (7508C)
Report of the Food Quality Protection Act
(FQPA) Tolerance Reassessment Progress
and Risk Management Decision (TRED) for
Cyhexatin
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, B.C. 20460
OFFICE OF
PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES
CERTIFIED MAIL
Dear Registrant:
This is the Environmental Protection Agency's (hereafter referred to as EPA or the Agency)
"Report of the Food Quality Protection Act (FQPA) Tolerance Reassessment Progress and Risk
Management Decision for Cyhexatin," which was approved on June 13, 2005. This document is also
known as a Tolerance Reassessment Decision, or TRED. A Notice of Availability of this tolerance
reassessment decision and an announcement of a 30-day public comment period will be published in the
Federal Register.
Introduction
The Federal Food, Drug and Cosmetic Act (FFDCA), as amended by FQPA, requires EPA to
reassess all the tolerances for registered chemicals in effect on or before the enactment of the FQPA on
August 3, 1996. In reassessing these tolerances, the Agency must consider, among other things,
aggregate risks from non-occupational sources of pesticide exposure, whether there is increased
susceptibility to infants and children, and the cumulative effects of pesticides with a common mechanism
of toxicity. Once a safety finding has been made, the tolerances are considered reassessed. Existing
tolerances associated with cyhexatin must be reassessed in accordance with FFDCA, as amended by
FQPA.
EPA has completed its review of the public comments on the risk assessment and is issuing its
risk management decision for cyhexatin. The last U.S. product registration was canceled in 1989, so
human exposure to this pesticide is strictly through the consumption of treated imported foods.
Residential and occupational exposures as well as dietary exposure through drinking water are not
expected because there is no domestic use of cyhexatin. Therefore, aggregate acute and chronic risk
are attributable only to the food sources from dietary exposure to imported food treated with cyhexatin.
There are currently 41 tolerances for cyhexatin. However, the manufacturers had indicated that
they were supporting only the tolerances for apple (fresh, juice, sauce, and dried) and citrus (orange
juice). The estimated acute dietary risks from use of cyhexatin on these commodities exceed the
Agency's level of concern. Because of this acute dietary concern, the manufacturers have withdrawn
support for all tolerances with the one exception of the orange juice tolerance.
1
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Safety Finding
EPA has evaluated the dietary risks from the importation of oranges to be processed into orange
juice and has determined that there is reasonable certainty that no harm to any population subgroup will
result from exposure to cyhexatin treated oranges. The acute dietary exposure estimate for orange juice
is below the Agency's level of concern. The most highly exposed sub-population was children 1-2
years of age, at 35% of the aPAD. Since the manufacturers have now indicated support for only orange
juice, all existing cyhexatin tolerances will be revoked and a tolerance will be established for orange,
juice. This tolerance will be time-limited pending submission and review of the necessary generic data.
Regulatory History
Cyhexatin (Case number 0237, active ingredient number 101601) is an organotin compound
used as an insecticide/acaricide to control mites on a variety of crops. There are 41 tolerances
established, under 40 CFR 180.144, for combined residues of cyhexatin and its organotin metabolites
for use on almonds, apples, citrus, hops, macadamia nuts, stone fruits, pears, strawberries, walnuts, and
animal commodities.
Cyhexatin was first registered in the U.S. in 1972 by the Dow Chemical Company for the
control of plant-feeding mites infesting fruit crops and ornamentals. The Cyhexatin Registration Standard
was issued in 1985. The last U.S. product registration was canceled in 1989. The current registrants
for cyhexatin outside the U.S. are Cerexagri Inc., and Oxon-Italia SpA.
In the Federal Register of January 21, 1998 (63 FR 3057) (FRL-5743- 8), EPA issued a
proposed rule for cyhexatin announcing the proposed revocation of all of the cyhexatin tolerances for
canceled active ingredients and inviting public comment for consideration and for support of tolerance
retention under FFDCA standards.
In response to the January 21, 1998 FR Notice four comments were received by the Agency to
support the tolerances and request the Agency not to proceed with revocation.
A comment was received by the Agency from Elf Atochem requesting that the tolerances for
cyhexatin not be revoked. Elf Atochem claimed it had pending applications for new registration. The
Agency received these applications for new product registrations in 1996 from Elf Atochem (now
Cerexagri Inc.), but they have since been withdrawn (4581-GIE, 45 81-GIG, and 4581-GIU).
A comment was received by the Agency from Oxon-Italia requesting that the tolerance for
cyhexatin on citrus not be revoked. Oxon-Italia stated it is developing residue data for submission to the
Agency. In follow-up correspondence to the Agency, Oxon-Italia, through its agent, further committed
to provide the data required to maintain the tolerances of cyhexatin on imported citrus crops. The data
have been evaluated and the results are presented in this TRED document.
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A comment was received by the Agency from the California Citrus Quality Council (CCQC)
requesting that the tolerance for cyhexatin on citrus not be revoked. CCQC cited Elf Atochem's
submission that indicated data were being developed and concerns about imports into the United States.
As noted before, the data have been evaluated and the results are presented in this TRED.
A comment was received by the Agency from the U.S. Hop Industry Plant Protection
Committee requesting that the tolerance for cyhexatin on hops not be revoked, claiming that a section 18
request was submitted for the 1998 growing season in Washington, Oregon, and Idaho. The last
Section 18 for use of cyhexatin on hops was issued in 1999 for the states of Washington and Idaho. In
the year 2000 a request for use of cyhexatin on hops was denied due to worker risks. No further
requests for the use of cyhexatin on hops have been submitted.
In summary, because of Cerexagri's and Oxon-Italia's interests in developing the data necessary
to maintain the existing tolerances EPA did not revoke the cyhexatin tolerances. This decision was
published in the Federal Register on October 26, 1998 (63 FR 57062) (FRL-6035-8).
In 1999 a tolerance petition (9E6053) was received from Cerexagri, Inc., to support tolerances
with no U.S. registrations (import tolerances) on apples and grapes.
In the fall of 2004, at the cyhexatin SMART meeting, the manufacturers Cerexagri Inc., and
Oxon-Italia, indicated their intention to support only the apple and citrus tolerances for import purposes.
The estimated acute dietary risks from use of cyhexatin on oranges to be processed into juice, and on
apples (fresh, juice, sauce, and dried), at the registered rates in Argentina, Brazil, and Chile exceed the
Agency's level of concern. However, the estimated dietary risks from use of cyhexatin only on oranges
to be processed into orange juice does not exceed the Agency's level of concern.
The cyhexatin preliminary dietary risk assessment with the supporting documents was released
to the public on November 10, 2004 (69 FR 65178) (FRL-7684-6) with a 60 day commenting period.
In addition to the comments submitted by the manufacturers, there were 29 comments submitted by
Brazilian government officials, academia, growers and businessmen in support of the continued use of
cyhexatin on citrus in Brazil. There were no comments submitted, other than by the manufacturers, for
the support of the use of cyhexatin on apples.
In light of this information both Cerexagri Inc., and Oxon-Italia have withdrawn support for all
tolerances with the one exception of the citrus tolerance. Since the manufacturers have now indicated
support for only orange juice, all existing cyhexatin tolerances will be revoked and a tolerance will be
established for orange, juice. This tolerance will be time-limited pending submission and review of
necessary generic data requirements listed in this document.
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Cumulative Risk Assessment
FQPA requires that EPA consider "available information" concerning the cumulative effects of a
particular pesticide's residues and "other substances that have a common mechanism of toxicity." The
Agency considers other substances because low-level exposures to multiple chemical substances that
cause a common toxic effect by a common mechanism could lead to the same adverse health effect, as
would a higher level of exposure to any of the other substances individually.
EPA does not have, at this time, available data to determine whether cyhexatin has a common
mechanism of toxicity with other substances. Unlike other pesticides for which EPA has followed a
cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common
mechanism of toxicity finding as to cyhexatin and any other substances and cyhexatin does not appear to
produce a toxic metabolite produced by other substances which have tolerances in the U. S. For the
purposes of this tolerance reassessment action, therefore, EPA has not assumed that cyhexatin has a
common mechanism of toxicity with other substances. For information regarding EPA's efforts to
determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects
of such chemicals, see the policy statements released by EPA's OPP concerning common mechanism
determinations and procedures for cumulating effects from substances found to have a common
mechanism on EPA's website at: http://www.epa.gov/fedrgstr/EPA-PEST/2002/January/Day-16/.
Health Effects
Cyhexatin has moderate acute toxicity by the oral route (Category U), and is highly irritating to
the skin and eyes. Dermal toxicity studies demonstrated dermal histopathology at the lowest doses
administered (0.1 mg/kg/day).
Available data in rats indicate that the liver is the major target organ (effects include changes in
organ weight and histopathological findings, especially in the bile duct, at 1 mg/kg/day in the chronic rat
study - the lowest dose tested). Body weight loss was also seen consistently in the rat studies, and
nervous system pathology was seen in a chronic study. The main target organs in dogs appear to be
heart, kidney and liver.
In accordance with EPA's Guidelines for Carcinogen Risk Assessment, cyhexatin is classified as
"data are inadequate for an assessment of human carcinogenic potential," based on consideration of both
mouse and rat cancer studies. Liver tumors in female rats provide, at most, suggestive evidence of
carcinogenicity. Tumors were adenomas only, were seen in only one sex and at one dose level, which
may be excessive. No pre-neoplastic lesions were noted in the rat study.
In the mouse carcinogenicity study, no treatment-related tumors were seen in males or females,
however, dosing may not have been high enough in both sexes to assess the carcinogenic potential of
cyhexatin. A sub-chronic toxicity study in mice is necessary and will address uncertainty related to the
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adequacy of the dosing in the mouse cancer study. There is no concern for mutagenicity associated with
cyhexatin. For a complete discussion of the cyhexatin cancer assessment see, "CYHEXATIN: Report
of the Cancer Assessment Review Committee," dated April 7, 2005.
The cyhexatin data base for prenatal developmental toxicity consist of one rat and eight rabbit
studies. The reproductive toxicity data base consists of a two multi-generation reproduction studies and
a 1-generation reproduction study. The NOAELs (No observed adverse effect level) and LOAELs
(lowest observed adverse effect level) used in the cyhexatin risk assessment were determined based on
a weight-of-evidence evaluation of all available developmental and reproduction studies.
Cyhexatin is a developmental toxicant producing effects in some cases at doses lower than
maternally toxic doses. The specific effect was hydrocephaly with a developmental toxicity NOAEL of
0.5 mg/kg/day (based on a synthesis of results of 4 of the developmental toxicity studies in rabbits) and a
LOAEL of 0.75 mg/kg/day, the lowest dose of the 3 rabbit studies in which hydrocephaly was noted.
Studies were conducted by both oral and dermal routes of administration. Maternal toxicity was seen at
the same or higher doses. Maternal toxicity was noted as mortality, abortions, increased post-
implantation loss, and decreased body weight gain.
In the rat developmental study no developmental toxicity was noted at the dose levels tested.
Maternal toxicity was noted as decreased body weight and food consumption and increased liver
weight.
In reproduction studies in rats, pup toxicity consisting of decreased pup weight was seen at
doses that also caused decreased body weight and food consumption in parental animals. Decreased
litter size was noted at a higher dose level in one reproduction study. There was no evidence of
increased susceptibility in any of the multi-generation reproduction studies in rats.
For a complete discussion of the results of the all the cyhexatin developmental and reproduction
studies see, "Cyhexatin: Toxicology Chapter of the Tolerance Reassessment Eligibility Decision
Document (TRED)", dated April 20, 2005 or the Cyhexatin: HED Chapter of the Tolerance
Reassessment Eligibility Decision Document (TRED), dated April 21, 2005.
With respect to the Food Quality Protection Act, the special FQPA factor was reduced to Ix
for acute dietary exposure scenarios because of the robust developmental and reproductive data base
indicating no residual uncertainties for pre- or post-natal toxicity. The Agency has determined that
dietary exposure estimates are conservative and unlikely to underestimate the potential risk for infants
and children.
However, for cyhexatin there are data gaps for a developmental neurotoxicity study and a rat
oral subchronic study. An assessment of the appropriate data base uncertainty factor (DB^) for the
DNT requirement, for the aRfD, both for females 13-49 and for the general population was conducted.
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The dose analysis for determining the DB^ for the DNT requirement was based on the 13 -week
neurotoxicity study in the rat and on a rat reproduction study and on the distribution of NOAELs and
LOAELs and dose levels in these studies. Based on these comparisons, a Ix DB^ safety factor for
aRfD for females 13-49 was selected. Similarly, based on the dose analysis, the acute dietary RfD for
general population required a 3x DB^ safety factor.
Table 1 . Studies Used in Dose Analysis Procedure
Study
Rat- 13-week
neurotoxicity study
Rat - 2-Generation
reproduction study
Doses (mg/kg/day)
0, 0.5, 2, 11
0, 0.1, 0.5, 6
NOAEL
2.0 mg/kg/day
0.5 mg/kg/day
LOAEL
1 1 mg/kg/day
6 mg/kg/day (both for
offspring and adults)
The Dose Analysis procedure is based, in this instance, on the NOAELs of 0.5 mg/kg/day in the
rat 2-generation study and the NOAEL of 0.5 mg/kg/day (below the higher NOAEL of 2 mg/kg/day) in
the 13 -week neurotoxicity study in the rat.
For endpoint selection, the aRfD for females 13-49 is based on the NOAEL of 0.5 mg/kg/day in
a rabbit developmental study. This aRfD has the same value as the NOAELs (0.5 mg/kg/day) from the
two above studies, so no data base uncertainty factors are needed.
For the aRfD for the general population, the selected NOAEL of 2 from the 13 -week
neurotoxicity needs to be divided by a 3x DB^, resulting in a value of 0.6 mg/kg/day, which is
comparable to the 0.5 mg/kg/day NOAELs from the above 2 studies.
For the chronic RfD, an assessment of the appropriate DB^ safety factor for the DNT
requirement was also conducted. The cRfD is based on the NOAEL of 0.25 mg/kg/day from the 1-
year dog study. The cRfD of 0.25 mg/kg/day based on the 1-year dog study is already less than 0.5
mg/kg/day in the rat 13-week neurotoxicity study and the rat reproduction study and, therefore, no
is needed.
A summary of the lexicological dose and endpoints for cyhexatin that were used in the dietary
risk assessment is shown below in Table 2.
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Table 2. Toxicological Dose and Endpoints used in the Dietary Risk Assessment
Exposure
Scenario
Acute Dietary
(Females 13-49
years of age)
Acute Dietary b
(general population)
Chronic Dietary
(All populations)
Dose Used in Risk
Assessment, UF
NOAEL = 0.5
mg/kg/day
UF = 100
Acute RfD = 0.005
mg/kg/day
NOAEL =1.99
mg/kg/day
UF = 300
Acute RfD = 0.0067
mg/kg/day
NOAEL= 0.25
mg/kg/day
UF = 100
Chronic RfD =
0.0025 mg/kg/day
Special FQPA SFa and
Level of Concern for
Risk Assessment
FQPA SF = 1
aPAD = acute RfD
FQPA SF
= 0.005 mg/kg/day
FQPA SF = 1
aPAD = acute RfD
FQPA SF
= 0.0067 mg/kg/day
FQPA SF = 1
cPAD = chronic RfD
FQPA SF
= 0.0025 mg/kg/day
Study and Toxicological Effects
Rabbit Developmental Studies
LOAEL = 0.75 mg/kg/day based on
hydrocephalus.
(based on synthesis of results from 4
rabbit developmental studies)
1 3-week neurotoxicity study
LOAEL =10.94 mg/kg/day based on
decreased body weight and food
consumption, clinical signs, and
functional observational battery
findings.
One- Year Dog Study
LOAEL = 0.5 mg/kg/day based on
increased kidney weight
a FQPA SF = Special FQPA safety factor, NOAEL = no observed adverse effect level, PAD = population adjusted
dose (a = acute, c = chronic) RfD = reference dose.
UF = uncertainty factor, lOx for interspecies extrapolation, lOx for intraspecies variability, and 3x for lack of a
developmental neurotoxicity study and a rat oral subchronic study (for Acute Dietary, general population, and
subpopulations other than females 13-49).
bAn acute reference dose for the general population was based on the 13 week neurotoxicity study because an acute
neurotoxicity study was not available.
Acute and Chronic Dietary (food onM Exposure and Risk Assessment
An acute and chronic dietary risk assessment was conducted using the Dietary Exposure
Evaluation Model software with the Food Commodity Intake Database (DEEM-FCID™, Version
2.03), which uses food consumption data from the USDA's Continuing Surveys of Food Intakes by
Individuals (CSFH) from 1994-1996 and 1998.
Residues used in both the acute and chronic dietary exposure analyses were the highest average
field trial (HAFT) residues. For apples, field trials were conducted in France and Italy and for oranges
field trials were conducted in Brazil. Since these studies were conducted at lower than maximum labeled
application rates, the residues were adjusted to the maximum application rate for apples by using a
factor of 5x, and adjusted to account for the missing metabolite, monocyclohexylstannoic acid by using a
factor of 1.3x. Processing factors from the available processing studies were also adjusted for the
missing metabolite. The processing studies were included with the submission of the residue field trials
on apples and oranges. All apple and orange juice samples from the processing studies had non-
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detectable residues. An average of the reported processing factors was used (0.3x). A distribution of
the available field trial data was" not used because of residue chemistry data deficiencies.
A relatively conservative acute dietary exposure assessment was conducted for all supported
cyhexatin food uses (imported apples and orange juice). Because of residue chemistry database
deficiencies, high end field trial residues were used, modified by processing factors from cyhexatin
processing studies. The acute dietary exposure assessment was refined using percent imports and
percent of crop treated in the exporting countries. This assessment concludes that for all supported
commodities, the acute dietary exposure estimate is above the Agency's level of concern for children 1 -
2 years of age at 223 % of the aPAD at the 99.9th percentile; for all infants < 1 year of age at 187% of
the aPAD, and for children 3-5 years of age at 151% of the aPAD. Apple juice and apple sauces
were the risk drivers.
An additional acute dietary exposure analysis was performed for orange juice alone. The acute
dietary exposure estimates for this analysis were below the Agency's level of concern. The most highly
exposed sub-population was children 1-2 years of age, at 35% of the aPAD.
Similarly, a relatively conservative chronic dietary exposure assessment was conducted for all
supported cyhexatin food uses (imported apples and orange juice). The same residues were used as in
the acute dietary exposure assessment because of residue chemistry database deficiencies. Dietary risk
estimates are provided for the general U.S. population and various population subgroups. This
assessment concludes that for all supported commodities, the chronic dietary exposure estimates are
below the Agency's level of concern for all population subgroups. The chronic dietary exposure
estimate for the highest exposed population subgroup, children 1-2 years of age, is 6% of the cPAD.
Table 3. Summary of Dietary Exposure and Risk for Cyhexatin based on uses on apples and oranges (for orange
juice).
Population Subgroup a
General U.S. Population
All Infants (< 1 yr)
Children 1-2 yrs
Children 3-5 yrs
Children 6-12 yrs
Youth 13-1 9 yrs
Adults 20-49 yrs
Females 13-49 yrs
Acute Dietary (99.9thPercentile)b
aPAD,
mg/kg
0.007
0.007
0.007
0.007
0.007
0.007
0.007
0.005
Exposure,
mg/kg/day
0.004132
0.013101
0.015600
0.010587
0.005361
0.002537
0.001752
0.002035
% aPAD
59
187
223
151
77
36
25
41
Chronic Dietary
cPAD,
mg/kg/day
0.0025
Exposure,
mg/kg/day
0.000020
0.000087
0.000139
0.000085
0.000031
0.000014
0.000009
0.000010
% cPAD
1
4
6
3
1
1
<1
<1
a The values for the population with the highest risk for each type of risk assessment are bolded.
b The 99.9th percentile is used because field trial residues, % imports, and % crop treated were used as the residue
inputs.
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Table 4 Summary of Dietary Exposure and Risk for Cyhexatin based on current tolerance for citrus only.
Population Subgroup a
General U.S. Population
All Infants (< 1 yr)
Children 1-2 yrs
Children 3-5 yrs
Children 6-12 yrs
Youth 13-1 9 yrs
Adults 20-49 yrs
Females 13-49 yrs
Acute Dietary (99. 9th Percentile)b
aPAD, mg/kg
0.007
0.0005
Exposure, mg/kg/day °
0.000877
0.000907
0.002434
0.001809
0.001199
0.000862
0.000604
0.000645
% aPAD
13
13
35
26
17
12
9
13
a The values for the population with the highest risk for each type of risk assessment are bolded.
b The 99.9th percentile is used because anticipated residues, % crop treated, and % imports were used as the residue
inputs.
Aggregate Risk and Risk Characterization
In accordance with the FQPA, EPA must consider pesticide exposures and risks from three
major sources: food, drinking water, and residential exposures. In an aggregate assessment, exposures
from relevant sources are added together and compared to quantitative estimates of hazard (e.g., a
NOAEL or PAD). When aggregating exposures and risks from various sources, EPA considers both
the route and duration of exposure.
An aggregate risk assessment is not required for cyhexatin. Dietary exposure from imported
food is the only pathway being assessed. There are no U.S. registrations, and therefore no residential or
drinking water exposure is anticipated.
Tolerance Reassessment Summary
Tolerances for the combined residues of cyhexatin and its organotin metabolites (calculated as
cyhexatin) are established under 40 CFR §180.144. There are currently no registered uses of cyhexatin
in the United States. Since the manufacturers have indicated support for only orange juice all existing
cyhexatin tolerances will be revoked and a tolerance will be established for orange, juice. This tolerance
will be time-limited pending submission and review of necessary generic data requirements listed in this
TRED document. A summary of cyhexatin tolerance reassessment is presented in Table 5.
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Table 5. Tolerance Reassessment Summary for Cyhexatin.
Commodity
Almond
Almond, hulls
Apple
Cattle, fat
Cattle, kidney
Cattle, liver
Cattle, meat byproducts, except kidney
and liver
Cattle, meat
Citrus pulp, dried
Citrus, fruits
Goat, fat
Goat, kidney
Goat, liver
Goat, meat byproducts, except kidney
and liver
Goat, meat
Hog, fat
Hog, kidney
Hog, liver
Hog, meat byproducts, except kidney
and liver
Hog, meat
Hop
Hop, dried
Horse, fat
Horse, kidney
Horse, liver
Horse, meat byproducts, except kidney
and liver
Horse, meat
Current Tolerance
Listed in 40 CFR
§ 180.1 44 (ppm)
0.5
60
2
0.2
0.5
0.5
0.2
0.2
8
2
0.2
0.5
0.5
0.2
0.2
0.2
0.5
0.5
0.2
0.2
30
90
0.2
0.5
0.5
0.2
0.2
Reassessed
Tolerance (ppm)
Revoke
Revoke
Revoke
Revoke
Revoke
Revoke
Revoke
Revoke
Revoke
Revoke
Revoke
Revoke
Revoke
Revoke
Revoke
Revoke
Revoke
Revoke
Revoke
Revoke
Revoke
Revoke
Revoke
Revoke
Revoke
Revoke
Comments
[Correct Commodity Definition}
No registered or proposed uses
No registered or proposed uses
No registered or proposed uses
Tolerances are not needed for use
of cyhexatin on citrus in Brazil
Commodity not expected to be
imported into the U. S.
Commodity not expected to be
imported into the U. S.
Tolerances are not needed for use
of cyhexatin on citrus in Brazil
No registered or proposed uses
Tolerances are not needed for use
of cyhexatin on citrus in Brazil
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Table 5. Tolerance Reassessment Summary for Cyhexatin.
Commodity
Milk, fat (=N in whole milk)
Nectarine
Nut, macadamia
Peach
Pear
Plum, prune, dried
Plum, fresh prune
Sheep, fat
Sheep, kidney
Sheep, liver
Sheep, meat byproducts, except kidney
and liver
Sheep, meat
Strawberry
Walnut
Current Tolerance
Listed in 40 CFR
§ 180.1 44 (ppm)
0.05
4
0.5
4
2
4
1
0.2
0.5
0.5
0.2
0.2
3
0.5
Reassessed
Tolerance (ppm)
Revoke
Revoke
Revoke
Revoke
Revoke
Revoke
Revoke
Revoke
Revoke
Revoke
Revoke
Revoke
Revoke
Revoke
Comments
[Correct Commodity Definition}
No registered or proposed uses.
No registered or proposed uses.
No registered or proposed uses.
No registered or proposed uses.
No registered or proposed uses
No registered or proposed uses
Tolerances are not needed for use
of cyhexatin on citrus in Brazil
No registered or proposed uses.
No registered or proposed uses.
Cyhexatin Tolerances Proposed to be Published in 40 CFR §180.144
Apple, wet pomace
Citrus, oil
Orange, juice
6
44
do not publish
do not publish
0.1
6H5463; commodity will not be
imported
6H5463; commodity will not be
imported
Orange juice is the only citrus
commodity to be imported
Additional Generic Data Requirements
The toxicology data gaps for cyhexatin are:
1) Subchronic mouse - this study will be used to reevaluate the dose levels in the mouse
carcinogenicity study.
2) Acute Neurotoxicity.
3) A Developmental Neurotoxicity study is not required at this time. This study will be required
if the use is to be expanded beyond the orange juice tolerance.
The residue chemistry data gaps for cyhexatin are:
1) Analytical method for all residues of concern. The current analytical method detects
cyhexatin, per se, and dicyclohexyloxostannane (DCTO). The method does not include
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monocyclohexylstannoic acid (MCTA). The analytical method needs to be rewritten to include
MCTA, and validation data must be provided.
2) Multiresidue method data.
3) Processing studies reflecting analysis for all residues of concern. The processing studies do
not include analysis for monocyclohexylstannoic acid (MCTA). The samples must be
reanalyzed for MCTA, and storage stability data must be provided.
4) Livestock feeding studies may be required if the use is to be expanded.
This document summarizes the Agency's decision on the tolerance reassessment for cyhexatin.
Please contact Tom Myers of my staff with any questions regarding this decision. He may be reached
by phone at (703) 308-8589 or by e-mail at myers.tom@epa.gov.
Sincerely,
Debra Edwards, Ph.D.
Director Special Review and Reregistration Division
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Technical Support Documents
for the Cyhexatin TRED
1. Susan V. Hummel (USEPA/OPPTS/OPP/HED). Cyhexatin: HED Chapter of the Tolerance
Reassessment Eligibility Decision Document (TRED). PC Code: 101601. Reregistration Case
No. 0237. April 21, 2005.
2. Susan V. Hummel (USEPA/OPPTS/OPP/HED). Cyhexatin: Residue Chemistry Summary for
the Tolerance Reassessment Eligibility Decision Document (TRED) and a Proposal for the
Establishment of Import Tolerances for Citrus Juice and Concentrate, and Apples. April 15,
2005.
3. Jessica Kidwell, (USEPA/OPPTS/OPP/HED). Cyhexatin: Report of the Cancer Assessment
Review Committee, PC Code: 101601, April 7, 2005.
4. Thurston G. Morton (USEPA/OPPTS/OPP/HED). Cyhexatin Revised Acute and Chronic
Dietary Exposure Assessment for the Tolerance Reassessment Eligibility Decision. May 5, 2005.
5. William Dykstra (USEPA/OPPTS/OPP/HED). Cyhexatin: Toxicology Chapter of the Tolerance
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