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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)-
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) * * *

                                                                              
                                                                              
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Commodity                              Parts per   
                                        million    
---------------------------------------------------------------------------                                                                              
                                                                              
Barley, straw ............................0.2  
                                                                              
Oat, straw................................0.2  
                                                                              
Wheat, straw..............................0.2  
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[FR Doc. 94-21256 Filed 8-30-94; 8:45 am]