[Federal Register Volume 59, Number 168 (Wednesday, August 31, 1994)]
[Unknown Section]
[Page 0]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-21256]
[[Page Unknown]]
[Federal Register: August 31, 1994]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[PP 4F4320/R2061; FRL-4780-4]
RIN No. 2070-AB78
Pesticide Tolerances for Beta-(4-Chlorophenoxy)-Alpha-(1,1-
Dimethylethyl)-1H-1,2,4-Triazole-1-Ethanol
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This rule establishes increased tolerances for the combined
residues of the fungicide beta-(4-chlorophenoxy)-alpha-(1,1-
dimethylethyl)-1H-1,2,4-triazole-1-ethanol, hereafter referred to as
triadimenol, and its butanediol metabolite, 4-(4-chlorophenoxy)-2,2-
dimethyl-4-(1H-1,2,4-triazol-l-yl)-1,3-butanediol, calculated as
parent, in or on the raw agricultural commodities (RACs) wheat straw,
barley straw, and oat straw at 0.2 part per million (ppm). This rule to
establish maximum permissible levels of combined residues of the
pesticide and certain of its metabolites in or on the commodities was
requested by Miles, Inc.
EFFECTIVE DATE: This regulation becomes effective August 31, 1994.
ADDRESSES: Written objections and hearing requests, identified by the
document control number, [PP 4F4320/R2061], may be submitted to:
Hearing Clerk (1900), Environmental Protection Agency, Rm. M3708, 401 M
St., SW., Washington, DC 20460. A copy of any objections and hearing
request filed with the Hearing Clerk should be identified by the
document control number and submitted to: Public Response and Program
Resources Branch, Field Operations Division (7505C), Office of
Pesticide Programs, Environmental Protection Agency, 401 M St., SW.,
Washington DC 20450. In person, bring copy of objections and hearing
request to: Rm. 1132, CM #2, 1921 Jefferson Davis Hwy., Arlington, VA
22202. Fees accompanying objections shall be labeled ``Tolerance
Petition Fees'' and forwarded to: EPA Headquarters Accounting
Operations Branch OPP (Tolerance Fees), P.O. Box 360277M, Pittsburgh,
PA 15251.
FOR FURTHER INFORMATION CONTACT: By mail: Cynthia Giles-Parker, Product
Manager (PM) 22, Registration Division, Environmental Protection
Agency, 401 M St., SW., Washington, DC 20460. Office location and
telephone number: Rm. 229, CM #2, 1921 Jefferson Davis Hwy., Arlington,
VA 22202, (703)-305-5540.
SUPPLEMENTARY INFORMATION: EPA issued a notice, published in the
Federal Register of June 29, (59 FR 33504), which announced that Miles,
Inc., 8400 Hawthorn Rd., P.O. Box 4913, Kansas City, MO 64120-0013, had
submitted pesticide petition (PP) 4F4320 to EPA proposing to amend 40
CFR 180.450 to increase the tolerances for the fungicide beta-(4-
chlorophenoxy)-alpha-(1,1-dimethylethyl)-1H-1,2,4-triazole-1-ethanol
and its butanediol metabolite, 4-(4-chlorophenoxy)-2,2-dimethyl-4-(1H-
1,2,4-triazol-l-yl)-1,3-butanediol, calculated as parent, in or on
wheat straw, barley straw, and oat straw from 0.1 part per million
(ppm) to 0.2 ppm. These tolerances were established under section 408
of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a.
There were no comments received in response to the notice of
filing.
The data submitted in support of the petition and other relevant
materials have been evaluated. The toxicological data considered in
support of the tolerances include the following:
1. A 2-year feeding/carcinogenicity study with rats using dietary
concentrations of 0, 125, 500, and 2,000 ppm, equivalent to 0, 6.25,
25.0, and 100 milligrams/kilogram (mg/kg) body weight (bwt)/day in
males and females. Clinical chemistry findings suggest that the target
organ for toxicity may be the liver. The levels of serum glutamic
oxaloacetate transaminase (SGOT) and serum glutamic pyruvic
transaminase (SGPT) were consistently higher at 2,000 ppm in males and
females when compared to untreated controls, and some increase in these
two parameters was also observed at 500 ppm. Although there was an
accompanying small increase in liver weight at 2,000 ppm in females,
there were no accompanying increases in histopathologic changes of the
liver in either sex. There were only marginal effects seen on other
clinical chemistry parameters, and no effect of the test compound was
seen on clinically observed signs of toxicity, food consumption,
hematology, or urinalysis parameters. The systemic no-observed-effect
level (NOEL) is 125 ppm (6.25 mg/kg/day for males and females) based on
the increase in liver enzymes (SGOT and SGPT). The systemic lowest-
effect level (LEL) was 500 ppm (25 mg/kg/day for males and females).
The chemical was not carcinogenic to rats under the testing conditions.
2. A 2-year chronic feeding/carcinogenicity study in mice using
dietary concentrations of 0, 125, 500, and 2,000 ppm (equivalent to
doses of 0, 18, 72, and 285 mg/kg/day for males and females). The
results of blood chemistry, organ weights, and gross and histological
examinations indicate that the liver is the target organ. There were
time- and dose-related increases in serum alkaline phosphatase (SAP),
SGOT, and SGPT activities in both male and female animals receiving 500
and 2,000 ppm of the test material.
In addition, increased incidence of enlarged livers, hyperplastic
nodules, and increased liver weights in both male and female animals
receiving 2,000 ppm of test material was detected at necropsy. Female
animals receiving 2,000- ppm doses exhibited a significant increase in
the incidence of liver adenomas only, a compound-related oncogenic
effect which is discussed further below. In males, there were no
differences in the incidence of these lesions in treated and control
males, and the incidences of liver adenomas were similar to those
observed in historical controls.
Based on blood chemistry findings, the systemic NOEL and the LEL
are 125 and 500 ppm, respectively (equivalent to 18 and 72 mg/kg/day
for males and females).
3. A 2-year male and female dog feeding study using doses of 0,
150, 600, and 2,400 ppm (equivalent to 0, 3.75, 15, and 60 mg/kg bwt/
day for males and females). The NOEL is 150 ppm based on changes in
enzyme levels (equivalent to 3.75 mg/kg bwt/day for males and females).
The LEL is 600 ppm. Although there were significant decreases in mean
body weights in males receiving 150 and 2,400 ppm and in females
receiving 600 and 2,400 ppm, the biological significance of these
changes could not be assessed. There were noted increases in alkaline
phosphatase N-demethylase and cytochrome P-450 in males receiving 2,400
ppm and significant increases in N-demethylase in females receiving 600
and 2,400 ppm and in cytochrome P-450 in females receiving 2,400 ppm
when compared to controls.
4. A 6-month dog feeding study using doses of 0, 10, 30, and 100
ppm (equivalent to 0, 0.25, 0.75, and 2.5 mg/kg bwt/day for males and
females). The NOEL was 2.5 mg/kg, the highest dose level tested (HDT).
5. A 3-month rat feeding study using doses of 0, 150, and 600 and
2,400 ppm (equivalent to 0, 7.5, 30 and 120 mg/kg bwt/day for males and
females) demonstrated a decrease in body weight, in hematocrit values,
and in eosinophil count and medium cell hemoglobin and demonstrated an
increase in the high-dose group and a dose-related increase in liver
weight. The NOEL is 7.5 mg/kg and the LEL is 30 mg/kg.
6. A second 90-day rat feeding study using doses of 0, 120, 600,
and 3,000 ppm demonstrated piloerection lasting 1 month (month 1),
decreases in body weight gain and feed efficiency lasting 1 week (week
1), alterations in serum lipids, and increases in liver weight
(absolute and relative) and in incidences of liver hypertrophy and
fatty changes in the high-dose group and an increase in the incidence
of prostrate atrophy of slight severity in high-dose males. The NOEL
was 600 ppm, equivalent to 39.6 mg/kg/day for males and 46.4 mg/kg/day
for females and the lowest-observed-effect level (LOEL) was the HDT,
3,000 ppm, equivalent to 208.5 mg/kg/day for males and 221.1 mg/kg/day
for females.
7. A 3-month dog feeding study using doses of 0, 150, 600, and
2,400 ppm (equivalent to 0, 3.75, 15, and 60 mg/kg bwt/day for males
and females). Weight gain in all male groups and in the highest dose
female group was significantly less than the control. Alkaline
phosphatase in males and females showed a dose-related negative trend.
There were no gross pathological changes. Effects at 15 mg/kg included
an increase in serum cholesterol level in males. Although the NOEL
appeared to be less than 3.75 mg/kg, based on reduced body weight and
decreased alkaline phosphatase in males, the Agency has concluded that
effects below 15 mg/kg in the 2-year dog study were not biologically
significant and the longer-term study supersedes the 90-day dog study.
Therefore, the NOEL remains at 3.75 mg/kg.
8. A rat developmental study using dose levels of 0, 30, 60, and
120 mg/kg/day was determined to be core supplementary because the NOEL
for developmental toxicity (supernumerary ribs) was not definitively
established. The NOEL and LOEL for maternal toxicity for this study are
30 and 60 mg/kg/day, respectively, based on decreases in maternal body
weight, body weight gain, and food consumption at 60 and 120 mg/kg/day.
Increased embryolethality (embryotoxicity) was only observed at the
highest dose level tested (120 mg/kg/day).
9. A repeat rat developmental study with a maternal NOEL of 5 mg/
kg/day and a LOEL of 15 mg/kg/day due to decreased body weight gains,
and with a developmental NOEL of 25 mg/kg/day and a LOEL of 60 mg/kg/
day due to increased incidence of extra ribs.
10. A supplementary rabbit developmental study with a NOEL for
maternal toxicity of 8 mg/kg and a maternal LEL of 40 mg/kg based on
decreased body weight gains and food consumption. The developmental
NOEL and LEL were 40 and 200 mg/kg, respectively.
11. A repeat rabbit developmental study with a maternal NOEL of 25
mg/kg/day and a LOEL of 125 mg/kg/day due to decreases in body weight
gains and food consumption, and with a developmental NOEL of 125 mg/kg/
day (HDT).
12. A reverse mutation assay (Ames), a dominant lethal test in
mice, DNA damage/repair, unscheduled DNA synthesis, in vitro and in
vivo (rat) cytogenic assays, and a forward mutation in mice, all of
which were negative for mutagenic effects.
13. A rat multi-generation reproduction study using doses of 0, 20,
100, and 500 ppm (equivalent to 0, 1, 5, and 25 mg/kg bwt/day for males
and females) indicated that the NOEL and LOEL for both parental and pup
toxicity are 100 and 500 ppm, respectively, based on significant body
weight and organ weight changes. The NOEL for reproductive toxicity is
500 ppm, the highest dose level tested. The Agency has concluded that
the available data provide limited evidence of the carcinogenicity of
triadimenol in mice and has classified the pesticide as a Category C
carcinogen (possible human carcinogen with limited evidence of
carcinogenicity in animals) in accordance with Agency guidelines,
published in the Federal Register in 1986 (51 FR 33992; September 24,
1986). This evaluation was confirmed by the Agency's Scientific
Advisory Panel on December 15, 1987. Based on a review of the Health
Effects Division Peer Review Committee for Carcinogenicity of the
Office of Pesticide Programs, the Agency has determined that a
quantitative risk assessment is not appropriate for the following
reasons:
1. The tumors observed were benign and observed in one sex
(females) and were present only at the highest dose tested.
2. The chemical was not carcinogenic when administered in the diet
to rats at dose levels ranging from 125 to 2,000 ppm.
3. The chemical was negative in the genotoxic assay battery.
Based on this evidence, EPA concludes that triadimenol poses at
most a negligible cancer risk to humans and that for purposes of risk
characterization the Reference Dose (RfD) approach should be used for
quantification of human risk. There are no processed commodities
derived from the RACs, wheat straw, barley straw and oat straw,
consequently no corresponding food or feed additive regulations are
required.
The standard risk assessment approach of using the Reference Dose
(RfD) based on systemic toxicity was applied to triadimenol. The
provisional acceptable daily intake (PADI) based on the 2-year dog
feeding studies (NOEL of 3.75 mg/kg bwt/day), and using a hundredfold
uncertainty factor, is calculated to be 0.038 mg/kg bwt/day. The
theoretical maximum residue contribution (TMRC) from established
tolerances is 0.000448 mg/kg/day and utilizes 1.2 percent of the PADI
for the U.S. population. For nonnursing infants and children, the TMRC
represents 2.8 and 2.6 percent of the PADI, respectively. These
tolerances will not change the TMRC or the dietary exposure analysis
because the already established meat and milk tolerances will cover any
dietary exposure from the increased tolerances in wheat straw, barley
straw, and oat straw.
The nature of the residue is adequately understood. The residues of
concern consist of the parent compound, beta-(4-chlorophenoxy)-alpha-
(1,1-dimethylethyl)-1H-1,2,4-triazole-1-ethanol and its butanediol
metabolite, 4-(4-chlorophenoxy)-2,2-dimethyl-4-(1H-1,2,4,-triazol-l-
yl)-1,3-butanediol, calculated as parent. Adequate analytical methods
are available for enforcement purposes. Methods are available in the
``Pesticide Analytical Manual,'' Vol. II (PAM II), for enforcement of
the tolerances on livestock commodities. The method for plants has been
submitted to the Food and Drug Administration for publication in PAM
II. Because of the long lead time from establishing this tolerance to
publication of the enforcement methodology in the PAM II, the
analytical methodology is being made available in the interim to anyone
interested in pesticide enforcement when requested from: Calvin Furlow,
Public Information Branch, Field Operations Division (7505C), Office of
Pesticide Programs, Environmental Protection Agency, 401 M St., SW.,
Washington, DC 20460. Office location and telephone number: Rm. 246, CM
#2, 1921 Jefferson Davis Hwy., Arlington, VA 22202, (703)-557-4432.
The pesticide is considered useful for the purposes for which the
tolerances are sought. Based on the information and data considered,
the Agency concludes that the establishment of the tolerances will
protect the public health. Therefore, the tolerances are established as
set forth below.
Any person adversely affected by this regulation may, within 30
days after publication of this document in the Federal Register, file
written objections and/or request a hearing with the Hearing Clerk, at
the address given above (40 CFR 178.20). A copy of the objections and/
or hearing requests filed with the Hearing Clerk should be submitted to
the OPP docket for this rulemaking. The objections submitted must
specify the provisions of the regulation deemed objectionable and the
grounds for the objections (40 CFR 178.25). Each objection must be
accompanied by the fees provided by 40 CFR 180.33(i). If a hearing is
requested, the objections must include a statement of the factual
issue(s) on which a hearing is requested, and the requestor's
contentions on each such issue, and a summary of the evidence relied
upon by the objection (40 CFR 178.27). A request for a hearing will be
granted if the Administrator determines that the material submitted
shows the following: there is a genuine and substantial issue of fact;
there is a reasonable possibility that available evidence identified by
the requestor would, if established, resolve on or more of such issues
in favor of the requestor, taking into account uncontested claims or
facts to the contrary; and resolution of the factual issue(s) in the
manner sought by the requestor would be adequate to justify the action
requested (40 CFR 178.32).
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, Recording and
recordkeeping requirements.
Dated: August 21, 1994.
Daniel M. Barolo,
Director, Office of Pesticide Programs.
40 CFR PART 180--[AMENDED]
Therefore, 40 CFR part 180 is amended as follows:
1. In part 180:
a. The authority citation for part 180 continues to read as
follows:
Authority: 21 U.S.C. 346a and 371.
2. Section 180.450(a) is amended in the table therein by revising
the entries for wheat straw, barley straw, and oat straw to read as
follows:
Sec. 180.450 Beta-(4-Chlorophenoxy)-alpha-(1,1-dimethylethyl)-1H-
1,2,4-triazole-1-ethanol; tolerances for residues.
(a) * * *
------------------------------------------------------------------------
Parts per
Commodity million
------------------------------------------------------------------------
*****
Barley, straw.............................................. 0.2
*****
Oat, straw................................................. 0.2
*****
Wheat, straw............................................... 0.2
------------------------------------------------------------------------
* * * * *
[FR Doc. 94-21256 Filed 8-30-94; 8:45 am]
BILLING CODE 6560-50-F