triadimenol (Baytan) Pesticide Tolerance 8/94
40 CFR Part 180
[PP 4F4320/R2061; FRL-4780-4]
RIN No. 2070-AB78
Pesticide Tolerances for Beta-(4-Chlorophenoxy)-Alpha-(1,1-Dimethylethyl)-
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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)-
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,
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-
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.
There were no comments received in response to the notice
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
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
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
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
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
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
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
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) * * *
Commodity Parts per
Barley, straw ............................0.2
* * * * *
[FR Doc. 94-21256 Filed 8-30-94; 8:45 am]