[Federal Register Volume 62, Number 30 (Thursday, February 13, 1997)]
[Notices]
[Pages 6780-6784]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-3646]
-----------------------------------------------------------------------
ENVIRONMENTAL PROTECTION AGENCY
[PF-708; FRL-5587-3]
ISK Biosciences Corporation; Pesticide Tolerance Petition Filing
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice of filing.
-----------------------------------------------------------------------
SUMMARY: This notice announces the filing of a pesticide petition
proposing the establishment of a regulation for residues of
chlorothalonil in or on almonds and almond hulls. The notice includes a
summary of the petition prepared by the petitioner, ISK Biosciences
Corporation.
DATES: Comments, identified by the docket number [PF-708], must be
received on or before March 17, 1997.
ADDRESSES: By mail, submit written comments to: Public Response and
Program Resources Branch, Field Operations Division (7506C), Office of
Pesticide Programs, Environmental Protection Agency, 401 M St., SW.,
Washington, DC 20460. In person, bring comments to Rm. 1132, CM #2,
1921 Jefferson Davis Highway, Arlington, VA.
Comments and data may also be submitted electronically by sending
electronic mail (e-mail) to: opp-docket@epamail.epa.gov. Comments and
data will also be accepted on disks in WordPerfect 5.1 file format or
ASCII file format. All comments and data in electronic form must be
identified by docket number [PF-708]. Electronic comments on this
notice of filing may be filed online at many Federal Depository
Libraries. Additional information on electronic submissions can be
found in Unit II. of this document.
Information submitted as comments 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. 1132 at the
address given above, from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays.
FOR FURTHER INFORMATION CONTACT: By mail: Cynthia Giles-Parker, Product
Manager (PM 22), Registration Division (7505C), Office of Pesticide
Programs, Environmental Protection Agency, 401 M St., SW., Washington,
DC 20460. Office location, telephone number, and e-mail address:
Crystal Mall #2, Room 229, 1921 Jefferson Davis Highway, Arlington, VA,
703-305-7740, e-mail: giles-parker.cynthia@epamail.epa.gov.
SUPPLEMENTARY INFORMATION: EPA has received a pesticide petition (PP
5F4558), originally published in the Federal Register on November 15,
1995 (60 FR 57419) (FRL-4971-5), from ISK Biosciences Corporation
(``ISK''), 5966 Heisley Road, P.O. Box 8000, Mentor, Ohio 44061,
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 180.275 by
establishing tolerances for residues of the fungicide chlorothalonil
and its metabolite, 4-hydroxy-2,5,6-trichloroisophthalonitrile (SDS-
3701) in or on the raw agricultural commodity (RAC) almonds (nutmeats)
at 0.05 parts per million (ppm) and almond hulls at 1.0 ppm. The
proposed analytical method is by electron capture gas chromatography.
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.
As required by section 408(d) of the FFDCA, as recently amended by
the Food Quality Protection Act (FQPA) Pub. L. 104-170, ISK included in
the petition a summary of the petition and authorization for the
summary to be published in the Federal Register in a notice of receipt
of the petition. The summary represents the views of ISK. EPA is in the
process of evaluating the petition. As required by section 408(d)(3) of
the FFDCA, EPA is including the summary as a part of this notice of
filing. EPA has made minor edits to the summary for the purpose of
clarity.
I. Petition Summary
A. Residue Chemistry Data
1. Plant/animal metabolism. The nature of the residue of
chlorothalonil in plants and animals, including ruminants, is well
understood. Chlorothalonil is not systemic in plants. Any
chlorothalonil residue found on almond nutmeats occurs as a surface
residue from transfer of the residue during harvesting and shelling
operations. Chlorothalonil is rapidly metabolized in the ruminant and
is not transferred to meat and milk from the dietary consumption by
animals. Furthermore, chlorothalonil is not stable in meat or milk.
2. Analytical method. An adequate analytical method (gas
chromatography) is available for enforcement purposes. The method is
listed in the Pesticide Analytical Manual, Vol. II (PAM II).
3. Magnitude of the residues. Residue data from studies conducted
with almonds support a tolerance of 0.05 ppm for combined residues of
chlorothalonil and its metabolite, 4-hydroxy-2,5,6-
trichloroisophthalonitrile in/on almond nutmeats and 1.0 ppm in/on
almond hulls. Residues of chlorothalonil on plants are surface
residues. Nutmeats are not systemically exposed to chlorothalonil since
chlorothalonil is not a systemic fungicide in plants. Chlorothalonil
residues are not directly translocated to the nutmeats, but residues
from the hulls that contaminate the almond shells during harvest may be
transferred to the nutmeats during the shelling process.
B. Toxicological Profile
The following studies on file with the Agency support this
petition.
1. Acute toxicity. Acute toxicity studies include an acute oral rat
study on technical chlorothalonil with an LD50 >10,000 milligram/
kilogram (mg/kg), an acute dermal toxicity study in the rabbit with an
LD50 >20,000 mg/kg, a 4-hour inhalation study with finely ground
technical chlorothalonil resulting in a LC50 of 0.092 mg/L (actual
airborne concentration), a primary eye irritation study with
irreversible eye effects in the rabbit at 21 days, a primary dermal
irritation study showing technical chlorothalonil is not a dermal
irritant, and a dermal sensitization study showing technical
chlorothalonil is not a skin sensitizer.
2. Genotoxicity. The mutagenic potential of chlorothalonil has been
evaluated in a large number of studies covering a variety of endpoints.
ISK concludes that chlorothalonil is not mutagenic.
Mutagenicity studies with chlorothalonil include gene mutation
assays in bacterial and mammalian cells; in vitro and in vivo
chromosomal aberration assays; DNA repair assays in bacterial systems;
and cell
[[Page 6781]]
transformation assays. All were negative with the following two
exceptions:
i. Chlorothalonil was positive in an in vitro chromosomal
aberration assay in CHO cells without metabolic activation but was
negative with metabolic activation.
ii. In vivo chromosomal aberration studies in rats and mice were
negative and one study in the Chinese hamster was equivocal. The
results of this study could not be confirmed in a subsequent study at
higher doses. The conclusion was that chlorothalonil does not cause
chromosome aberrations in bone marrow cells of the Chinese hamster. It
can be concluded that chlorothalonil does not have clastogenic
potential in intact mammalian systems.
In bacterial DNA repair tests chlorothalonil was negative in
Bascillus subtilis, but was positive in Salmonella typhimurium. In an
in vivo DNA binding study in rats, with 14C-chlorothalonil, there
was no covalent binding of the radiolabel to the DNA of the kidney,
which is the target organ for chlorothalonil toxicity in rodents.
3. Developmental and reproductive toxicity. A developmental
toxicity study with rats given gavage doses of 0, 25, 100, and 400 mg/
kg body weight (bwt)/day from days 6 through 15 of gestation resulted
in a no observed effect level (NOEL) for maternal toxicity of 100 mg/
kg/day based on increased mortality, reduced body weight, and a slight
increase in early resorptions at the highest dose. There were no
developmental effects observed at any dose in this study.
A developmental toxicity study in rabbits given gavage doses of 0,
5, 10, or 20 mg/kg/day on days 7 through 19 of gestation resulted in a
maternal NOEL of 10 mg/kg/day. Effects observed in the dams in the
high-dose group were decreased body weight gain and reduced food
consumption. There were no developmental effects observed in this
study.
A 2-generation reproduction study in rats fed diets containing 0,
500, 1,500 and 3,000 ppm resulted in a reproductive NOEL of 1,500 ppm
(equivalent to 115 mg/kg/day) based on lower neonatal body weights by
day 21. There were no effects seen on any other reproductive parameter
at any dose level in this study.
4. Subchronic toxicity. i. A 90-day subchronic toxicity study was
conducted in rats at doses of 0, 1.5, 3.0, 10, and 40 mg/kg bwt.
Treatment related hyperplasia and hyperkeratosis of the forestomach was
observed at the two highest dose levels. Although the initial
histopathological evaluation did not demonstrate any nephrotoxicity, a
subsequent evaluation observed a treatment-related increase in
hyperplasia of the proximal tubule epithelium at 40 mg/kg bwt in the
male rats but not in the females. The NOEL for renal histopathology was
10 mg/kg bwt in males and 40 mg/kg bwt in females.
ii. A 90-day oral toxicity study was conducted in dogs with dose
levels of technical chlorothalonil of 15, 150, and 750 mg/kg bwt/day.
The two highest dosages resulted in lower body weight gain in male
dogs. The NOEL was 15 mg/kg/day. There were no macroscopic or
microscopic tissue alterations related to chlorothalonil and there were
no signs of renal toxicity.
iii. Two 21-day dermal toxicity studies have been conducted with
technical chlorothalonil. In the initial study, doses of 50, 2.5, and
0.1 mg/kg bwt/day were administered to rabbits. The NOEL for systemic
effects was greater than 50 mg/kg bwt/day and the NOEL for dermal
irritation was 0.1 mg/kg bwt/day.
A subsequent 21-day dermal study was conducted in male rats to
specifically evaluate the potential for nephrotoxicity in this
laboratory species following dermal dosing. In this study the doses
were 60, 100, 250, and 600 mg/kg bwt/day. The NOEL for nephrotoxicity
was greater than 600 mg/kg bwt/day.
5. Estrogenic effects. Based upon all of the chronic toxicity,
teratogenicity, mutagenicity, and reproductive studies conducted with
chlorothalonil and its metabolites, ISK concludes that there were no
results which indicate any potential to cause estrogenic effects or
endocrine disruption. These effects would have manifested themselves in
these studies as reproductive or teratogenic effects or by producing
histopathological changes in estrogen sensitive tissues such as the
uterus, mammary glands, or the testes. Thus, ISK concludes based upon
the in vivo studies, that chlorothalonil does not cause estrogenic
effects.
6. Chronic toxicity. i. A 12-month chronic oral toxicity study in
Beagle dogs was conducted with technical chlorothalonil at dose levels
of 15, 150, and 500 mg/kg/day. The NOEL was 150 mg/kg/day based on
lower blood albumin levels at the highest dose. There was no
nephrotoxicity observed at any dose in this study. This study replaced
an old outdated study that was not conducted under current guidelines
and did not use the current technical material.
ii. A chronic feeding/carcinogenicity study with Fischer 344 rats
fed diets containing 0, 800, 1,600 or 3,500 ppm (equivalent to 0, 40,
80 or 175 mg/kg bwt/day) for 116 weeks in males or 129 weeks in
females, resulted in a statistically higher incidence of combined renal
adenomas and carcinomas. At the high dose, which was above the MTD,
there was also a statistically significant higher incidence of tumors
of the forestomach in female rats.
iii. In a second chronic feeding/carcinogenicity study with Fischer
344 rats, designed to define the NOEL for tumors and the preneoplastic
hyperplasia, animals were fed diets containing 0, 2, 4, 15 or 175 mg/
kg/day. The NOEL in this study, based on renal tubular hyperplasia, was
a nominal dose of 2 mg/kg bwt/day. Because of the potential for
chlorothalonil to bind to diet the 2 mg/kg bwt/day dose, expressed as
unbound chlorothalonil, is 1.8 mg/kg bwt/day. The NOEL for hyperplasia
and hyperkeratosis of the forestomach was 4 mg/kg bwt/day or a dose of
3.8 mg/kg bwt/day based on unbound chlorothalonil.
iv. A 2-year carcinogenicity study, conducted in CD-1 mice at
dietary levels of 0, 750, and 1,500 or 3,000 ppm (equivalent to 0, 107,
214 or 428 mg/kg/day), resulted in a statistically higher incidence of
squamous cell carcinomas of the forestomach in both sexes and a
statistically higher incidence of combined renal adenomas/carcinomas in
only the male mice receiving the low dose. There were no renal tumors
in any female mouse in this study.
v. A 2-year carcinogenicity study, in male CD-1 mice for the
purpose of establishing the NOEL for renal and forestomach effects, was
conducted at dietary levels of 0, 10/15, 40, 175, or 750 ppm
(equivalent to 0, 1.4/2.1, 5.7, 25 or 107 mg/kg/day). The NOEL for
renal effects was 40 ppm and the NOEL for forestomach effects was 15
ppm. This study did not duplicate the results from the previous study
where a statistically higher incidence of renal tumors, when compared
to controls, was observed at 750 ppm.
In 1987, the Office of Pesticide Programs' Toxicology Branch Peer
Review Committee classified chlorothalonil as a B2 (probable human
carcinogen) based on evidence of carcinogenicity in the forestomach and
kidneys of rats and mice. The Agency currently regulates chlorothalonil
as a B2 carcinogen although ISK has provided a significant amount of
mechanistic data indicating that the tumors result from a threshold
mechanism. A potency factor, Q1* (Q1
[[Page 6782]]
star), of 0.00766 (mg/kg/day)1 has been used by the Agency when
conducting mathematical modeling to estimate carcinogenic risk to man.
ISK believes that because the nephrotoxicity seen in the rat is due to
a threshold mechanism, any risk associated with chlorothalonil can be
managed using the margin of safety (exposure) approach.
---------------------------------------------------------------------------
1``Mechanistic Interpretation of the Oncogenicity of
Chlorothalonil in Rodents and an Assessment of Human Relevance,'' by
Drs. C. F. Wilkinson and J. C. Killeen, Regulatory Toxicology and
Pharmacology 24: 69-84 (1996), Article No. 006.
---------------------------------------------------------------------------
Numerous metabolism and toxicology studies indicate that
chlorothalonil is non-genotoxic and produces a species-specific renal
toxicity in the rat that eventually may lead to tumor formation through
an epigenetic mechanism. Studies comparing metabolism and toxicological
effects in dogs with those in rats demonstrate that the renal effects
observed in the rat are due to the exposure of the kidney of the rat to
significant levels of nephrotoxic thiol metabolites of chlorothalonil.
In the dog, no thio metabolites are found and there are no toxic
effects seen in kidneys of dogs dosed with high levels of
chlorothalonil.
7. Reference dose (RfD). The NOEL for chlorothalonil in the rat is
1.8 mg/kg bwt based on the nephrotoxicity observed in the chronic rat
study. The NOEL in the dog was 15 mg/kg bwt in the 90-day study and 150
mg/kg bwt based on the 1-year study. NOEL for maternal toxicity from
developmental studies are 10 mg/kg bwt in rabbits and 100 mg/kg bwt in
the rat. The NOEL for pup growth in the reproduction study was 1,500
mg/kg bwt, which would be most conservatively estimated as equating to
approximately 75 mg/kg bwt. Data indicate that the nephrotoxicity in
the rat is produced through a mechanism for which there is a clear
threshold. In a study which measured cell turnover in the rat kidney
with proliferating cell nuclear antigen (PCNA) immunohistochemical
staining, a NOEL was established at 1.5 mg/kg bwt. Other chronic
studies have established the NOEL for hyperplasia in the kidney to be
1.8 mg/kg bwt. If all the available toxicity data in laboratory animals
are considered without regards to its applicability to humans, the
lowest NOEL for any adverse effect would be 1.5 mg/kg bwt/day. Because
the mechanism of toxicity which is related to the tumor formation in
the kidney has been shown to have a threshold, the use of the normal
100-fold safety factor in conjunction with the 1.5 mg/kg NOEL would
produce a reference dose which would provide more than adequate safety
for all of the possible effects seen in any laboratory animal.
In two recent reviews of chlorothalonil by the Joint Meeting of
Pesticide Residue Experts (1990 and 1992) and the review by the World
Health Organization's International Program for Chemical Safety, these
esteemed groups concluded that the rat was not the appropriate species
to use in consideration of the risk assessment for man. They concluded
that the dog was the more appropriate species for determination of
subchronic and chronic effects. If the toxicological data for the dog
were used, the NOEL would be at least 15 mg/kg bwt, which is based on
the most recent 90-day study of the dog.
Therefore, under the most conservative scenario (using the
toxicological data in the rat), the reference dose would be 1.8 mg/kg
bwt/day divided by a 100-fold safety factor or 0.018 mg/kg bwt/day with
a threshold model being used for carcinogenic risk assessment. In the
scenario that uses the toxicological data of the dog, the reference
dose would be 15 mg/kg bwt/day divided by a safety factor of 100 or
0.15 mg/kg bwt/day.
C. Aggregate Exposure
The following is a description of the likelihood of exposure to
chlorothalonil from various routes.
1. Dietary exposure.-- i. Food. The Agency's Dietary Exposure
Analysis dated April 1, 1996, of ISK's petition (PP 5F4558), which
requested tolerances for chlorothalonil and its metabolite, 4-hydroxy-
2,5,6-trichloroisophthalonitrile (SDS-3701) in/on almond nutmeats and
almond hulls, determined the dietary exposure from the proposed new
anticipated residue contributed from almonds to be 0.000001 mg/kg bwt/
day to the U.S. population and also to children ages 1 to 6.
The Agency had calculated that the exposure of the general
population from existing published tolerances for chlorothalonil is
0.000133 mg/kg bwt/day and 0.00021 mg/kg bwt/day for infants and
children ages 1 to 6. Unfortunately, the Agency's calculation of the
total exposure contained a significant error. The Agency grossly
overestimated the exposure from the use of chlorothalonil on mushrooms
by using an anticipated residue of 2.54 ppm which constitutes an
illegal residue. The tolerance is 1.0 ppm. There were also other
overestimates of less magnitude in the April 1996 EPA document. ISK
believes that the correct exposure, based on the current registered
uses for chlorothalonil, is 0.0000642 mg/kg bwt/day for the general
population and 0.000105 mg/kg bwt/day for infants and children 1 to 6
years of age.
ii. Drinking water. Chlorothalonil was included for monitoring in
the National Survey of Pesticides in Drinking Water Wells conducted by
EPA. No chlorothalonil residues were detected in any of the 1,300
community water systems and domestic wells (using methodology for
chlorothalonil having a limit of detection (LOD) of 0.06 g/l
and limit of quantitation of 0.12 g/l). The absence of
chlorothalonil detections in the National Survey of Pesticides in
Drinking Water Wells provides adequate information to conclude that
chlorothalonil is not a contaminant in drinking water wells and that
the population is not exposed to chlorothalonil in these water sources.
These findings are consistent with the known physical/chemical
properties of chlorothalonil including low water solubility (0.9 ppm)
and high affinity for organic matter including soil. It has also been
demonstrated that chlorothalonil does not leach into groundwater from
applications made to growing crops.
Aerobic aquatic metabolism studies with chlorothalonil establish a
half-life in natural aquatic habitats of less than 10 hours, depending
on environmental conditions. Considering the short half-life of
chlorothalonil in natural water/sediment systems and that surface water
is filtered and treated prior to consumption, chlorothalonil is not
likely to be present in drinking water obtained from natural surface
water systems.
An exposure estimate, based on surface water concentration recently
cited by EPA, would conclude that the average concentration in surface
water would be less than 0.002 ppm. Assuming that everyone in the
United States consumed untreated surface water, the exposure to
chlorothalonil of the general population would be less than 5.8 x
10-7 mg/kg bwt/day. This would be a worse case scenario, which
would greatly overestimate exposure.
2. Non-dietary exposure. Potential non-dietary exposures to
chlorothalonil may result from the following uses of chlorothalonil. In
each case, the exposure would be from the dermal route and only for an
intermittent duration. The two 21-day dermal studies that have been
conducted in the rabbit and rat indicate that there is no
nephrotoxicity associated with the dermal exposure to chlorothalonil at
dose levels up to 600 mg/kg/day. Therefore, the exposures from the uses
of chlorothalonil listed below would not
[[Page 6783]]
be expected to add to the carcinogenic risk associated with
chlorothalonil.
i. Golf course uses. Chlorothalonil products are commonly applied
to golf course trees and greens to control a broad complex of turf
diseases. Application to golf course fairways is much less common. Golf
is not a game played by infants or small children, therefore no
exposure to infants and children would be anticipated.
ii. Residential owner uses. Applications of chlorothalonil products
to home lawns are rare. Thus, there is very little exposure to
chlorothalonil related to use on residential turf. Applications to
roses and other ornamentals in home gardens is also a minor use of
chlorothalonil.
iii. Paint. Chlorothalonil is used in paints and stains for control
of mildew and molds on exterior surfaces of buildings. Chlorothalonil
is also occasionally used for interior paints, but this use represents
only a small proportion of the chlorothalonil used in paints. About 2%
of the chlorothalonil used in paint is used in interior paint; however,
only 0.2% or less of interior paints in the United States contain
chlorothalonil. In paints chlorothalonil is tightly bound within the
paint matrices; thus, effective control of mildew may last for several
years and the potential for exposure is very limited.
iv. Grouts. Chlorothalonil is used in cement tile grouts and for
control of mildew and molds. Chlorothalonil is bound within the grout
matrices and very little is available for exposure. This is a minor use
of chlorothalonil and non-occupational dermal exposure of humans to
chlorothalonil from this source is extremely low.
v. Wood treatment. Chlorothalonil is not currently used for
pressure-treating wood. It is used for control of sapstain as a surface
treatment on rough-cut, newly-sawn lumber to protect it from molds and
mildews while drying. Being a surface residue, it is removed during the
finishing operations prior to sale of the wood. Chlorothalonil does not
occur in structural wood used for residential or occupational
scenarios.
D. Cumulative Effects
ISK has considered the potential for cumulative effects of
chlorothalonil and other substances that have a common mechanism of
toxicity. Chlorothalonil is a halogenated benzonitrile which readily
undergoes displacement of the 2, 4 and 6 chlorines by glutathione and
other thiol containing amino acids and proteins. In the rat, the thiol
metabolites are sufficiently absorbed to produce a nephrotoxic effect.
In dogs where this absorption does not occur, nephrotoxicity does not
occur. ISK does not have any information to indicate that toxic effects
observed in rats occur through a mechanism which is common to any other
agricultural chemical. Thus, consideration of common mechanisms of
toxicity is not appropriate at this time.
Chlorothalonil should not be confused with chlorinated hydrocarbon
pesticides which have significantly different chemical and biological
properties.
E. Safety Determination
1. U.S. population. In EPA's Dietary Exposure Analysis, dated April
1, 1996, for chlorothalonil and its metabolite in/on almond nutmeats
and almond hulls, the Agency determined that the oncogenic dietary
risks associated with potential exposure from anticipated residue of
0.05 ppm from almonds is minimal. The risk assessment concluded that
chlorothalonil does not pose a significant chronic or acute dietary
risk for uses that are currently published or for uses recommended by
EPA for registration. Unfortunately, the Agency's calculation of the
total exposure for existing published uses contained a significant
error. The Agency grossly overestimated the exposure from the use of
chlorothalonil on mushrooms by using an anticipated residue of 2.54 ppm
which constitutes an illegal residue. The tolerance is 1.0 ppm.
The Agency has used a linearized model to estimate the carcinogenic
risk associated with chlorothalonil, whereas ISK believes that a
threshold based model is appropriate. If the linearized multistage
model is used with the corrected exposure estimates for food presented
earlier, the carcinogenic risk would be estimated at 4.9 x 107
for the general population and 8.0 x 107 for infants and
children. Using the overestimated exposure estimates of EPA, with a
threshold based model and using the conservative RfD of 0.018 mg/kg
bwt/day, the margin of safety for the general population would exceed
10,000 and the margin of safety for infants and children would exceed
7,000. Using corrected exposure estimates would obviously yield larger
margins of exposure. Using a conservative RfD of 0.018 mg/kg/day, as
the Agency has done in recent Dietary Risk Evaluation System (DRES)
analyses, and incorporating corrections needed in exposure values for
mushrooms and several other lesser corrections, ISK calculated the
overall dietary exposure to anticipated residues of chlorothalonil,
from all registered uses and pending uses of chlorothalonil, to be
0.36% of the RfD for the general U.S. population and 0.59% of the RfD
for children ages 1 to 6 years old, which is the group with the highest
exposure.
Because the worse case assumption for human exposure from drinking
water indicates that exposure would be only 1% of the dietary exposure,
the risk assessment is not significantly altered by considering the
exposure from drinking water.
2. Infants and children. There is a complete data base for
chlorothalonil which includes pre- and post-natal developmental
toxicity data as well as mechanistic data related to the rodent
specific nephrotoxicity observed in subchronic and chronic studies. The
toxicological effects of chlorothalonil in rodents are well understood.
Chlorothalonil has a low level of toxicity in dogs.
In a 2-generation reproduction study in rats, all reproductive
parameters investigated showed no treatment-related effects except pup
weight gain. Specifically, the weights of pups exposed to
chlorothalonil were comparable to controls at parturition through day
four of lactation. It was only after day four of lactation, when the
pups begin to consume the test diet, that body weight gain lags behind
controls. This only occurred at the highest dose tested, which is 3,000
ppm. The dose of chlorothalonil the pups would receive would be far in
excess of the estimated adult dose of 150 mg/kg bwt/day (3,000 ppm
-20). The doses for the pups could have easily exceeded 500 mg/kg
bwt/day. Dose levels of 375 mg/kg bwt and above have been shown to
significantly affect body weight in the rat. Therefore, the reduction
of body weight gain observed in the reproduction study is considered to
be comparable to the effects that have been observed in older rats. The
NOEL for this effect was 1,500 ppm.
In developmental toxicity studies conducted in the rat and the
rabbit, chlorothalonil did not cause any developmental effects even at
dose levels that produced significant maternal toxicity. In the rabbit
a dose level of 20 mg/kg bwt caused maternal toxicity, but there were
no developmental effects and in the rat, a dose level of 400 mg/kg bwt
caused maternal toxicity without developmental toxicity.
The extensive data base that is available for chlorothalonil is
devoid of any indication that chlorothalonil would represent any
unusual or disproportionate hazard to infants or children. Therefore,
there is no need to impose an additional 10x safety factor
[[Page 6784]]
for infants or children. The standard uncertainty factor of 100x should
be used for all segments of the human population when calculating risks
associated with chlorothalonil.
F. International Tolerances
A maximum residue level has not been set for chlorothalonil on
almonds by the Codex Alimentarius Commission.
II. Public Record
EPA invites interested persons to submit comments on this notice of
filing. Comments must bear a notation indicating the docket number [PF-
708].
A record has been established for this notice of filing under
docket number [PF-708] 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 public record is located in Room 1132 of the Public
Response and Program Resources Branch, Field Operations Division
(7506C), Office of Pesticide Programs, Environmental Protection Agency,
Crystal Mall #2, 1921 Jefferson Davis Highway, Arlington, VA.
Electronic comments can be sent directly to EPA at:
opp-docket@epamail.epa.gov
Electronic comments must be submitted as ASCII file avoiding the
use of special characters and any form of encryption.
The official record for this notice of filing, as well as the
public version, as described above will be kept in paper form.
Accordingly, EPA will transfer all comments received electronically
into printed paper form as they are received and will place the paper
copies in the official record which will also include all comments
submitted directly in writing. The official record is the paper record
maintained at the address in ``ADDRESSES'' at the beginning of this
document.
List of Subjects
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.
Dated: February 7, 1997.
Donald R. Stubb,
Acting Director, Registration Division, Office of Pesticide Programs.
[FR Doc. 97-3646 Filed 2-12-97; 8:45 am]
BILLING CODE 6560-50-F
