[Federal Register Volume 61, Number 16 (Wednesday, January 24, 1996)]
[Proposed Rules]
[Pages 1884-1887]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-879]



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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180

[PP 0E3889, 2E4113, and 5E4538/P639; FRL-4990-6]
RIN 2070-AC18


Chlorothalonil; Pesticide Tolerances

AGENCY: Environmental Protection Agency (EPA).

ACTION: Proposed rule.

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SUMMARY: EPA proposes to establish tolerances for combined residues of 
the fungicide chlorothalonil and its metabolite in or on the raw 
agricultural commodities blueberries, filberts, and mushrooms. The 
proposed regulation to establish maximum permissible levels for 
residues of the fungicide was requested in petitions submitted by the 
Interregional Research Project No. 4 (IR-4) pursuant to the Federal 
Food, Drug and Cosmetic Act (FFDCA).

DATES: Comments, identified by the document control number [PP 0E3889, 
2E4113, and 5E4538/P639], must be received on or before February 23, 
1996.

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 22202. Comments and data 
may also be submitted electronically by sending electronic mail (e-
mail) to: [email protected] 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 the docket number [PP 
0E3889, 2E4113, and 5E4538/P639]. Electronic comments on this proposed 
rule may be filed online at many Federal Depository Libraries. 
Additional information on electronic submissions can be found below in 
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 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 a.m. to 4:30 p.m., Monday through Friday, excluding legal 
holidays.

FOR FURTHER INFORMATION CONTACT: By mail: Hoyt L. Jamerson, 
Registration Division (7505W), Office of Pesticide Programs, 
Environmental Protection Agency, 401 M St., SW., Washington, DC 20460. 
Office location and telephone number: Sixth Floor, Crystal Station #1, 
2800 Jefferson Davis Highway, Arlington, VA 22202, (703)-308-8783; e-
mail: [email protected].

SUPPLEMENTARY INFORMATION: The Interregional Research Project No. 4 
(IR-4), New Jersey Agricultural Experiment Station, P.O. Box 231, 
Rutgers University, New Brunswick, NJ 08903, has submitted pesticide 
petitions (PP) 0E3889, 2E4113, and 5E4538 to EPA on behalf of the named 
Agricultural Experiment Stations. These petitions request that the 
Administrator, pursuant to section 408(e) of the Federal Food, Drug, 
and Cosmetic Act (FFDCA), 21 U.S.C. 346a(e), amend 40 CFR 180.275 by 
establishing tolerances for combined residues of the fungicide 
chlorothalonil (tetrachloroisophthalonitrile) and its metabolite 4-
hydroxy-2,5,6-trichloroisophthalonitrile in or on certain raw 
agricultural commodities, as follows:
    1. PP 0E3889. Petition submitted on behalf of the Agricultural 
Experiment Stations of Florida, Georgia, Kentucky, Louisiana, Michigan, 
North Carolina, Oklahoma, Pennsylvania, South Carolina, Tennessee, 
Texas, and Washington proposing a tolerance for blueberries at 1.0 part 
per million (ppm).
    2. PP 2E4113. Petition submitted on behalf of the Oregon 
Agricultural Experiment Station proposing a tolerance for filberts at 
0.1 ppm. The petitioner proposed that use of chlorothalonil on filberts 
be limited to Oregon based on the geographical representation of the 
residue data submitted. Additional residue data will be required to 
expand the area of usage. Persons seeking geographically broader 
registration should contact the Agency's Registration Division at the 
address provided above.
    3. PP 5E4538. Petition submitted on behalf of the Pennsylvania 
Agricultural Experiment Station proposing a tolerance for mushrooms at 
1.0 ppm.
    The scientific data submitted in the petitions and other relevant 
material have been evaluated. The toxicological data considered in 
support of the 

[[Page 1885]]
proposed tolerances include the following data:
    1. A 3-month feeding study in rats fed diets containing 175 
milligrams (mg)/kilogram (kg)/day with gastric and renal lesions in 
male rats.
    2. A 2-year feeding study in dogs fed diets containing 0, 60, or 
120 ppm with a NOEL of 60 ppm (1.8 mg/kg/day) based on the induction of 
kidney vacuolated epithelium and increased bilirubin levels at the 120 
ppm (3.5 mg/kg/day) dose level.
    3. A chronic feeding/carcinogenicity study with Fisher 344 rats fed 
diets containing 0, 800, 1,600, or 3,500 ppm (equivalent to 0, 40, 80, 
or 175 mg/kg/day) for 116 weeks in males or 129 weeks in females 
resulted in a statistically significant increase in the incidence of 
renal adenoma and carcinoma, with a significant dose-related trend in 
both sexes. In female rats there was also a statistically significant 
increase in papilloma and combined papilloma/carcinoma of the 
forestomach with significant dose-related trend for combined papilloma/
carcinoma.
    4. A second chronic feeding/carcinogenicity study with Fisher 344 
rats fed diets containing 0, 2, 4, 15, or 175 mg/kg/day with a NOEL of 
2 mg/kg/day based on increased kidney weight, possible increase in 
kidney tubular lesions, increase in renal tubular adenomas and 
carcinomas, increased incidence and/or severity of hyperplasia, 
hyperkeratosis and ulcers of squamous mucosa of forestomach at the 4 
mg/kg/day dose level. There were also increases in the incidence of 
renal tubular adenomas and carcinomas; increases in the incidence and 
severity of kidney tubular lesions; and hyperplasia, hyperkeratosis, 
and ulcers/erosions of squamous mucosa of the forestomach of rats fed 
diets containing 15 and 175 mg/kg/day.
    5. A 2-year carcinogenicity study in CD-1 mice fed diets containing 
0, 750, 1,500, or 3,000 ppm (equivalent to 0, 107, 214, or 428 mg/kg/
day) that resulted in statistically significant increases in squamous 
cell carcinoma of the forestomach in both sexes, with a positive dose-
related trend for combined papilloma/carcinoma in females, and 
statistically significant increases in the incidence of combined renal 
adenoma/carcinoma in dosed male mice.
    6. A 2-year feeding/carcinogenicity study in male CD-1 mice fed 
diets containing 0, 10/15, 40, 175, or 750 ppm (equivalent to 0, 1.4/
2.1, 5.7, 25, or 107 mg/kg/day), which resulted in a slight increase in 
tubular hyperplasia at 175 ppm, and hyperplasia and hyperkeratosis of 
the squamous mucosa of the forestomach at 750 ppm.
    7. A developmental toxicity study with rats given gavage doses of 
0, 25, 100, and 400 mg/kg/of body weight/day from days 6 through 15 of 
gestation with a NOEL for maternal toxicity at 100 mg/kg/day based on 
increased mortality, reduced body weight, and increased resorptions and 
post implantation losses. There were no developmental effects observed 
under the conditions of the study.
    8. 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 with a 
maternal NOEL of 10 mg/kg/day. Effects observed in rabbits in the high-
dose group (20 mg/kg/day) were decreased body weight gain and reduced 
food consumption. There were no developmental effects observed in this 
study.
    9. A two-generation reproduction study in rats fed diets containing 
0, 500, 1,500, and 3,000 ppm with a reproductive NOEL of 1,500 ppm 
(equivalent to 115 mg/kg/day) based on lower neonatal body weights by 
day 21.
    10. Mutagenicity studies were negative in the following acceptable 
assays: rat, mouse and hamster in vivo chromosomal aberration tests; 
Salmonella assays with and without activation; and mouse and rat in 
vivo cytogenetics assays. A weak positive response was elicited with 
chlorothalonil in an in vivo Chinese hamster bone marrow cytogenetics 
assay, which did not show a dose-response.
    11. A general metabolism study in rats shows that oral absorption 
of aqueous suspensions of chlorothalonil is low. At a dose levels equal 
to or less than 50 mg/kg/day the majority of chlorothalonil was 
excreted in the feces as chlorothalonil within 24 hours. At a dose 
level of 200 mg/kg/day the rate of chlorothalonil excretion and levels 
in the blood are prolonged. Major detoxification occurs in the liver, 
by conjugation with glutathione. Although these conjugates are excreted 
directly into the bile, some may be transported to the kidneys where 
they are converted to thiol metabolites, the excretion of which is rate 
limited, and thus may lead to nephrotoxicity (and possible tumor 
formation) when overloading occurs.
    The Office of Pesticide Programs' Toxicology Branch Peer Review 
Committee met on May 28, 1987, to evaluate the weight-of-evidence on 
chlorothalonil, with particular reference to its carcinogenic 
potential. The weight-of-evidence relating to the carcinogenicity of 
chlorothalonil at that time included the following:
    i. A 2-year carcinogenicity study in Osborne-Mendel rats fed diets 
containing 0, 253, or 506 mg/kg/day, which resulted in a statistically 
significant increase in combined renal adenoma/carcinoma in both sexes, 
with a significant dose-related trend in female rats.
    ii. The chronic feeding/carcinogenicity study with Fisher 344 rats 
(item 3, above).
    iii. The 2-year carcinogenicity study in CD-1 mice (item 5, above).
    The Committee classified chlorothalonil as a B2 carcinogen 
(probable human carcinogen) in accordance with EPA's guidelines for 
carcinogenic risk assessment (51 FR 33992, September 24, 1986). This 
decision was based on increased incidences of malignant and/or combined 
malignant/benign tumors (in both sexes) in two species (rat and mouse).
    The Scientific Advisory Panel met on September 23, 1987 to consider 
the Agency's Toxicology Branch Peer Review Committee decision regarding 
the carcinogenicity of chlorothalonil. The Panel did not comment 
specifically on the Agency's evaluation and classification of 
chlorothalonil, although it did agree that the renal tumors in the CD-1 
male mouse were biologically significant at concentrations below the 
maximum-tolerated dose.
    The Toxicology Branch Peer Review Committee met again on May 9, 
1988, to consider for the second time the classification of 
carcinogenicity for chlorothalonil. At that time, the Committee 
considered all submitted data, including interim reports (after 1 year) 
for the following studies:
    iv. A 2-year dietary feeding study in Fisher 344 rats fed diets 
containing (0, 2, 4, 15, or 175 mg/kg/day) with interim findings of 
hyperplasia and karyomegaly of the renal cortex in males at 4, 15, and 
175 mg/kg/day, and in females at 175 mg/kg/day; and squamous epithelial 
hyperplasia and hyperkeratosis of the gastric mucosa in both sexes at 
15 and 75 mg/kg/day. See item 4 (above) for results of full 2-year 
study.
    v. A 2-year carcinogenicity study in Charles River CD-1 male mice 
fed diets containing 0, 10, 40, 175, or 750 ppm (equivalent to 0, 107, 
214, or 428 mg/kg/day) with a slight increase in renal tubular 
hyperplasia at 175 ppm, and hyperplasia and hyperkeratosis of the 
squamous mucosa of the forestomach at 750 ppm. See item 6 (above) for 
results of full 2-year study.
    The Committee concluded that the evidence satisfies the criteria 
contained in the EPA Guidelines for sufficient 

[[Page 1886]]
evidence of carcinogenicity and reaffirmed its classification of 
chlorothalonil as a Group B2 (probable human carcinogen).
    As currently manufactured, chlorothalonil is contaminated with 
hexachlorobenzene (HCB) at levels that may accumulate in plants due to 
repeated applications of chlorothalonil. HCB is classified as a group 
B2, probable human carcinogen, by the Cancer Assessment Group. Animal 
feeding studies with HCB show an increased incidence of malignant 
tumors in two species: haemangioendothelioma in hamsters and 
hepatocellular carcinoma in rats, as well as confirmed reports of 
hepatomas in both of these species.
    Dietary risk assessments for chlorothalonil and HCB indicate that 
there is minimal risk from established tolerances and the proposed 
tolerances for blueberries, filberts, and mushrooms. Dietary risk 
assessments were conducted using Reference Doses (RfD) and the 
applicable cancer potency factors to assess chronic exposure and risk 
from chlorothalonil and HCB residues, and the Margin of Exposure (MOE) 
to asses acute toxicity from chlorothalonil residues.
    The Reference Dose (RfD) for chlorothalonil is established at 0.018 
mg/kg of body weight (bwt)/day, based on a NOEL of 1.8 mg/kg/day from 
the 2-year feeding study in dogs and an uncertainty factor of 100. 
Available information on anticipated residues and/or percent of crop 
treated was incorporated into the analysis to estimate the Anticipated 
Residue Contribution (ARC) from existing uses. Tolerance-level residues 
and 100-percent crop treated were assumed to estimate dietary exposure 
from the proposed uses for blueberries, filberts, and mushrooms. The 
ARC is generally considered a more realistic estimate than an estimate 
based on tolerance-level residues and 100-percent crop treated. The ARC 
from existing uses and the proposed uses utilizes less than 1 percent 
of the RfD for the U.S. population and all population subgroups.
    The RfD for HCB is established at 0.0008 mg/kg/day based on a NOEL 
of 0.08 mg/kg of body weight/day and an uncertainty factor of 100. The 
NOEL was taken from a 130-week feeding study in rats that showed 
hepatic centrilobular basophilic chromogenesis. Since there are no 
published tolerances for HCB, the ARC was calculated by multiplying the 
anticipated residues for chlorothalonil by 0.05 percent, an adjustment 
based on comparisons of residue data for the two compounds from 
controlled field trials. The ARC for HCB from existing uses of 
chlorothalonil and the proposed uses on blueberry, filberts, and 
mushrooms utilizes less than 1 percent of the RfD for the U.S. 
population and less than 2 percent of the RfD for children, aged 1 to 6 
(the population subgroup at greatest risk).
    The upper-bound carcinogenic risks were calculated using the ARC 
estimates for dietary exposure from existing uses; tolerance level 
residues from the proposed uses on blueberries, filberts, and 
mushrooms; and Q*s of 0.00766 (mg/kg/day)-1 for 
chlorothalonil and 1.02 (mg/kg/day)-1 for HCB. The upper-bound 
carcinogenic risk from existing uses and the proposed uses of 
chlorothalonil is estimated at 7.7 X 10-7 with the proposed uses 
contributing 2.4 X 10-7 to the cancer risk assessment. The upper-
bound carcinogenic risk for HCB is estimated at 1.9 X 10-7 for 
existing uses and the proposed uses, with the proposed uses 
contributing 1.8 X 10-8 to the cancer risk assessment.
    The MOE is a measure of how closely the high-end acute dietary 
exposure comes to the NOEL from the toxicity endpoint of concern. For 
chlorothalonil, the MOE was calculated as ratio of the lowest-observed-
effect level (LOEL) of 175 mg/kg/day from the subchronic study in rats. 
A NOEL was not established since an effect (renal and gastric lesions) 
was observed at the single dose tested. An uncertainty factor of 300 
was used to calculate the MOE since there was no available NOEL from 
the study. The acute dietary margin of exposure from chlorothalonil is 
calculated to be greater than 300 for the general population and all 
population subgroups. Chlorothalonil poses minimal acute dietary risk.
    The nature of the residue in blueberries, filberts, and mushrooms 
is adequately understood. The parent compound and its metabolite (4-
hydroxy-2,5,6-trichloroisophthalonitrile) are of regulatory concern. An 
adequate analytical method (gas chromatography) is available for 
enforcement purposes. The method is listed in the Pesticide Analytical 
Manual, Vol. II (PAM II). There are currently no actions pending 
against the registration of this chemical.
    There is no reasonable expectation that secondary residues will 
occur in milk, eggs, or meat of livestock and poultry since there are 
no livestock feed items associated with blueberries, filberts, or 
mushrooms.
    Based on the information and data considered, the Agency has 
determined that the tolerances established by amending 40 CFR part 180 
would protect the public health. Therefore, it is proposed that the 
tolerances be established as set forth below.
    Any person who has registered or submitted an application for 
registration of a pesticide, under the Federal Insecticide, Fungicide, 
and Rodenticide Act (FIFRA) as amended, which contains any of the 
ingredients listed herein, may request within 30 days after publication 
of this document in the Federal Register that this rulemaking proposal 
be referred to an Advisory Committee in accordance with section 408(e) 
of the FFDCA.
    A record has been established for this rulemaking under docket 
number [PP 0E3889, 2E4113, 5E4538/P639] (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 a.m. to 4:30 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-D[email protected]
    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.
    Under Executive Order 12866 (58 FR 51735, Oct. 4, 1993), the Agency 
must determine whether the regulatory action is ``significant'' and 
therefore subject to all the requirements of the Executive Order (i.e., 
Regulatory Impact Analysis, review by the Office of Management and 
Budget (OMB)). Under section 3(f), the order defines ``significant'' as 
those actions likely to lead to a rule (1) having an annual effect on 
the economy of $100 million or more, or adversely and materially 
affecting a sector of the economy, productivity, competition, 

[[Page 1887]]
jobs, the environment, public health or safety, or State, local or 
tribal governments or communities (also known as ``economically 
significant''); (2) creating serious inconsistency or otherwise 
interfering with an action taken or planned by another agency; (3) 
materially altering the budgetary impacts of entitlement, grants, user 
fees, or loan programs; or (4) raising novel legal or policy issues 
arising out of legal mandates, the President's priorities, or the 
principles set forth in this Executive Order.
    Pursuant to the terms of this Executive Order, EPA has determined 
that this rule is not ``significant'' and is therefore not subject to 
OMB review.
    Pursuant to the requirements of the Regulatory Flexibility Act 
(Pub. L. 96-354, 94 Stat. 1164, 5 U.S.C. 601-612), the Administrator 
has determined that regulations establishing new tolerances or raising 
tolerance levels or establishing exemptions from tolerance requirements 
do not have a significant economic impact on a substantial number of 
small entities. A certification statement to this effect was published 
in the Federal Register of May 4, 1981 (46 FR 24950).

List of Subjects in 40 CFR Part 180

    Environmental protection, Administrative practice and procedure, 
Agricultural commodities, Pesticides and pests, Reporting and 
recordkeeping requirements.

    Dated: December 15, 1995.

Peter Caulkins,
Acting Director, Registration Division, Office of Pesticide Programs.

    Therefore, it is proposed that 40 CFR part 180 be amended as 
follows:

PART 180--[AMENDED]

    1. The authority citation for part 180 continues to read as 
follows:

    Authority: 21 U.S.C. 346a and 371.

    2. In Sec. 180.275, by amending paragraph (a) in the table therein 
by adding entries for blueberries and mushrooms and by amending 
paragraph (b) in the table therein by adding an entry for filberts, to 
read as follows:


Sec. 180.275   Chlorothalonil; tolerances for residues.

    (a) *  *  *

------------------------------------------------------------------------
                                                              Parts per 
                         Commodity                             million  
------------------------------------------------------------------------
                                                                        
                  *        *        *        *        *                 
Blueberries................................................          1.0
                                                                        
                  *        *        *        *        *                 
Mushrooms..................................................          1.0
                                                                        
                  *        *        *        *        *                 
------------------------------------------------------------------------

    (b) *  *  *

------------------------------------------------------------------------
                                                              Parts per 
                         Commodity                             million  
------------------------------------------------------------------------
                                                                        
Filberts...................................................          0.1
                                                                        
                  *        *        *        *        *                 
------------------------------------------------------------------------


[FR Doc. 96-879 Filed 1-23-96; 8:45 am]
BILLING CODE 6560-50-F