[Federal Register Volume 62, Number 63 (Wednesday, April 2, 1997)]
[Notices]
[Pages 15700-15704]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-8388]


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ENVIRONMENTAL PROTECTION AGENCY
[PF-726; FRL-5594-9]


ISK Biosciences Corporation; Pesticide Tolerance Petition Filing

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice of filing.

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SUMMARY: This notice announces the initial filing of a pesticide 
petition proposing the establishment of time-limited tolerances for 
residues of the fungicide, chlorothalonil and its metabolite, 4-
hydroxy-2,5,6-trichloroisophthalonitrile in or on non-bell peppers. 
This notice includes a summary of the petition that was prepared by the 
petitioner, ISK Biosciences Corporation.

DATES: Comments, identified by the docket control number [PF-726], must 
be received on or before, May 2, 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 be sending 
electronic mail (e-mail) to: <a href="/cdn-cgi/l/email-protection#036c73732e676c60686677436673626e626a6f2d6673622d646c75"><span class="__cf_email__" data-cfemail="711e01015c151e121a1405311401101c10181d5f1401105f161e07">[email protected]</span></a>. Electronic 
comments must be submitted as an ASCII file avoiding the use of special 
characters and any form of encryption. 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 
control number [PF-726]. Electronic comments on this notice 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 a comment concerning this document may be 
claimed confidential by marking any part or all of that information as 
``Confidential Business Information'' (CBI). CBI should not be 
submitted through e-mail. Information marked as CBI will not be 
disclosed except in accordance with procedures set forth in 40 CFR part 
2. A copy of the comment

[[Page 15701]]

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 (7505W), Office of Pesticide 
Programs, Environmental Protection Agency, 401 M St., SW., Washington, 
DC 20460. Office location, telephone number, and e-mail address: Rm. 
229, CM #2, 1921 Jefferson Davis Highway, Arlington, VA, (703) 305-
6226; e-mail: <a href="/cdn-cgi/l/email-protection#55323c3930262534273e30277b362c3b213d3c341530253438343c397b3025347b323a23"><span class="__cf_email__" data-cfemail="dcbbb5b0b9afacbdaeb7b9aef2bfa5b2a8b4b5bd9cb9acbdb1bdb5b0f2b9acbdf2bbb3aa">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION: EPA has received a pesticide petition (PP 
6F4676) from ISK Biosciences Corporation, 5966 Heisley Road, P.O. Box 
8000, Mentor, Ohio 44061-8000 proposing pursuant to section 408(d) of 
the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. section 346a(d), to 
amend 40 CFR 180.275 by establishing a time-limited tolerance for a 
period of 2 years for residues of the fungicide chlorothalonil and its 
metabolite, 4-hydroxy-2,5,6-trichloroisophthalonitrile in or on the raw 
agricultural commodity non-bell peppers at 5.0 parts per million (ppm). 
ISK Biosciences Corporation has committed to providing additional 
residue data during this 2-year period from trials conducted in Mexico 
in support of a permanent tolerance. 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); 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, ISK Biosciences Corporation 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 Biosciences 
Corporation. EPA is in the process of evaluating the petition. As 
required by section 408(d)(3), 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. ISK Biosciences' 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 non-bell peppers occurs as a surface 
residue. 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 non-bell peppers support a tolerance of 5.0 ppm for combined 
residues of chlorothalonil and its metabolite, 4-hydroxy-2,5,6-
trichloroisophthalonitrile in or on the raw agricultural commodity.

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 LD<INF>50 >10,000 milligrams/
kilograms (mg/kg), an acute dermal toxicity study in the rabbit with an 
LD<INF>50 >20,000 mg/kg, a 4-hour inhalation study with finely ground 
technical chlorothalonil resulting in a LC<INF>50 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. 
The overall conclusion is 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 transformation assays. All were negative with the following 
two exceptions:
    Chlorothalonil was positive in an in vitro chromosomal aberration 
assay in CHO cells without metabolic activation but was negative with 
metabolic activation.
    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 
Bacillus subtilis, but was positive in Salmonella typhimurium. In an in 
vivo DNA binding study in rats with <SUP>14C-chlorothalonil, there was 
no covalent binding of the radiolabel to the DNA of the kidney, 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/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 two-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 subchronic toxicity study (90 days) 
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 no effect level for renal 
histopathology was 10

[[Page 15702]]

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 no observed adverse effect level (NOAEL) 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, 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, it can be concluded 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 NOAEL 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 no effect level 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 level 
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, EPA's 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 Biosciences Corporation 
has provided a significant amount of mechanistic data indicating that 
the tumors result from a threshold mechanism. A potency factor, Q1*, of 
0.00766 (mg/kg/day)<SUP>-1 has been used by the Agency when conducting 
mathematical modeling to estimate carcinogenic risk to man. ISK 
Biosciences Corporation 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.
    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.<SUP>1 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 thiol metabolites are found and there 
are no toxic effects seen in kidneys of dogs dosed with high levels of 
chlorothalonil.
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    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.
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    7. Reference Dose (RfD). The no effect level for chlorothalonil in 
the rat is 1.8 mg/kg bwt based on the nephrotoxicity observed in the 
chronic rat study. The no effect level in the dog was 15 mg/kg bwt in 
the 90-day study and 150 mg/kg bwt based on the one-year study. No 
effect levels for maternal toxicity from developmental studies are 10 
mg/kg bwt in rabbits and 100 mg/kg bwt in the rat. The no effect level 
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 bromodeoxyuridine 
(BRDU) 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 is 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 no effect level would produce a RfD 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 
Heath Organization's International Program for Chemical Safety, these

[[Page 15703]]

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, based on the most 
recent 90-day study in the dog.
    Therefore, under the most conservative scenario (using the 
toxicological data in the rat), the RfD 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 in 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. ISK Biosciences Corporation has 
conducted a dietary exposure analysis for chlorothalonil and its 
metabolite, 4-hydroxy-2,5,6-trichloroisophthalonitrile (SDS-3701) in or 
on non-bell peppers utilizing EPA's Dietary Risk Evaluation System 
(DRES) based on the 1977-78 Food Consumption Survey. The results 
demonstrate that the dietary exposure from anticipated residues of 0.5 
ppm contributed from non-bell peppers is 0.00000218 mg/kg bwt/day for 
the U.S. population or 0.0121% of the RfD.
    The Agency had calculated that the exposure of the general 
population from existing published tolerances for chlorothalonil is 
0.000134 mg/kg bwt/day or 0.744 percent of the RfD.
    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 mg/l and limit 
of quantitation of 0.12 mg/l). The absence of chlorothalonil detections 
in the National Survey 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 ppb. Assuming that everyone in the U.S. 
consumed untreated surface water, the exposure to chlorothalonil of the 
general population would be less than 5.8 x 10<SUP>-7 mg/kg bwt/day. 
This would be a worst 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 be expected to add to the 
carcinogenic risk associated with chlorothalonil.
    i. Golf course uses. Chlorothalonil products are commonly applied 
to golf course tees 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, also 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 Biosciences 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 Biosciences 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. ISK Biosciences Corporation has conducted a 
risk assessment for chlorothalonil in or on non-bell peppers using the 
1977-78 Food Consumption Survey and a potency factor, Q1*, of 0.00766 
(mg/kg/day)<SUP>-1 and has determined that oncogenic dietary risks 
associated with

[[Page 15704]]

potential exposure using an anticipated residue of 0.5 ppm, would 1.7 x 
10<SUP>-8.
    The Agency has used a linearized model to estimate the carcinogenic 
risk associated with chlorothalonil, whereas ISK Biosciences believes 
that a threshold based model is appropriate. 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 
DRES analyses, and incorporating corrections needed in exposure values 
for mushrooms and several other lesser corrections, ISK Biosciences 
Corporation 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.
    Because the worst case assumption for human exposure from drinking 
water indicate 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 two-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 4 
of lactation. It was only after day 4 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; 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 divided by 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 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

    There is currently no maximum residue level set for chlorothalonil 
on non-bell peppers by the Codex Alimentarius Commission.

II. Public Record

    A record has been established for this notice under docket control 
number [PF-726] (including comments and data submitted electronically 
as described below). A public version of the 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 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:
    <a href="/cdn-cgi/l/email-protection#573827277a3338343c3223173227363a363e3b7932273679303821"><span class="__cf_email__" data-cfemail="462936366b2229252d2332062336272b272f2a6823362768212930">[email protected]</span></a>
    Electronic comments must be submitted as an ASCII file avoiding the 
use of special characters and any form of encryption.
    The official record for this rulemaking, 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 rulemaking record which will also include all comments 
submitted directly in writing. The official rulemaking 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: March 24, 1997.
Stephen L. Johnson,
Director, Registration Division, Office of Pesticide Programs.
[FR Doc. 97-8388 Filed 4-1-97; 8:45 am]
BILLING CODE 6560-50-F


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