[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] ----------------------------------------------------------------------- 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. ----------------------------------------------------------------------- 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