[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