Proposed Rules. Notice
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/register/2001/08/01/01-19169A research copy — for the controlling text, always check the official state or federal source. Not legal advice.
BILLING CODE 6560-50-S ENVIRONMENTAL PROTECTION AGENCY [PF-1032; FRL-6789-2] Notice of Filing a Pesticide Petition to Establish a Tolerance for a Certain Pesticide Chemical in or on Food AGENCY: Environmental Protection Agency (EPA). ACTION: Notice. SUMMARY: This notice announces the initial filing of a pesticide petition proposing the establishment of regulations for residues of a certain pesticide chemical in or on various food commodities. DATES: Comments, identified by docket control number PF-1032, must be received on or before August 31, 2001.
ADDRESSES: Comments may be submitted by mail, electronically, or in person. Please follow the detailed instructions for each method as provided in Unit I.C. of the SUPPLEMENTARY INFORMATION . To ensure proper receipt by EPA, it is imperative that you identify docket control number PF-1032 in the subject line on the first page of your response. FOR FURTHER INFORMATION CONTACT: By mail: Cynthia Giles-Parker, Fungicide Branch, Registration Division (7505C), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460; telephone number:
(703)305-7740; e-mail address: giles-parker.cynthia@epa.gov. SUPPLEMENTARY INFORMATION: I. General Information A. Does this Action Apply to Me? You may be affected by this action if you are an agricultural producer, food manufacturer or pesticide manufacturer. Potentially affected categories and entities may include, but are not limited to: Categories NAICS codes Examples of potentially affected entities Industry 111 Crop production 112 Animal production 311 Food manufacturing 32532 Pesticide manufacturing This listing is not intended to be exhaustive, but rather provides a guide for readers regarding entities likely to be affected by this action. Other types of entities not listed in the table could also be affected. The North American Industrial Classification System (NAICS) codes have been provided to assist you and others in determining whether or not this action might apply to certain entities. If you have questions regarding the applicability of this action to a particular entity, consult the person listed under FOR FURTHER INFORMATION CONTACT . B. How Can I Get Additional Information, Including Copies of this Document and Other Related Documents? 1. *Electronically* . You may obtain electronic copies of this document, and certain other related documents that might be available electronically, from the EPA Internet Home Page at http://www.epa.gov/. To access this document, on the Home Page select “Laws and Regulations,” “Regulations and Proposed Rules,” and then look up the entry for this document under the “ **Federal Register** —Environmental Documents.” You can also go directly to the **Federal Register** listings at http://www.epa.gov/fedrgstr/. 2. *In person* . The Agency has established an official record for this action under docket control number PF-1032. The official record consists of the documents specifically referenced in this action, any public comments received during an applicable comment period, and other information related to this action, including any information claimed as confidential business information (CBI). This official record includes the documents that are physically located in the docket, as well as the documents that are referenced in those documents. The public version of the official record does not include any information claimed as CBI. The public version of the official record, which includes printed, paper versions of any electronic comments submitted during an applicable comment period, is available for inspection in the Public Information and Records Integrity Branch (PIRIB), Rm. 119, Crystal Mall #2, 1921 Jefferson Davis Highway, Arlington, VA, from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The PIRIB telephone number is
(703)305-5805. C. How and to Whom Do I Submit Comments? You may submit comments through the mail, in person, or electronically. To ensure proper receipt by EPA, it is imperative that you identify docket control number PF-1032 in the subject line on the first page of your response. 1. *By mail* . Submit your comments to: Public Information and Records Integrity Branch (PIRIB), Information Resources and Services Division (7502C), Office of Pesticide Programs (OPP), Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460. 2. *In person or by courier* . Deliver your comments to: Public Information and Records Integrity Branch (PIRIB), Information Resources and Services Division (7502C), Office of Pesticide Programs (OPP), Environmental Protection Agency, Rm. 119, Crystal Mall #2, 1921 Jefferson Davis Highway, Arlington, VA. The PIRIB is open from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The PIRIB telephone number is
(703)305-5805. 3. *Electronically* . You may submit your comments electronically by e-mail to: opp-docket@epa.gov, or you can submit a computer disk as described above. Do not submit any information electronically that you consider to be CBI. Avoid the use of special characters and any form of encryption. Electronic submissions will be accepted in Wordperfect 6.1/8.0 or ASCII file format. All comments in electronic form must be identified by docket control number PF-1032. Electronic comments may also be filed online at many Federal Depository Libraries. D. How Should I Handle CBI That I Want to Submit to the Agency? Do not submit any information electronically that you consider to be CBI. You may claim information that you submit to EPA in response to this document as CBI by marking any part or all of that information as CBI. Information so marked will not be disclosed except in accordance with procedures set forth in 40 CFR part 2. In addition to one complete version of the comment that includes any information claimed as CBI, a copy of the comment that does not contain the information claimed as CBI must be submitted for inclusion in the public version of the official record. Information not marked confidential will be included in the public version of the official record without prior notice. If you have any questions about CBI or the procedures for claiming CBI, please consult the person identified under FOR FURTHER INFORMATION CONTACT . E. What Should I Consider as I Prepare My Comments for EPA? You may find the following suggestions helpful for preparing your comments: 1. Explain your views as clearly as possible. 2. Describe any assumptions that you used. 3. Provide copies of any technical information and/or data you used that support your views. 4. If you estimate potential burden or costs, explain how you arrived at the estimate that you provide. 5. Provide specific examples to illustrate your concerns. 6. Make sure to submit your comments by the deadline in this notice. 7. To ensure proper receipt by EPA, be sure to identify the docket control number assigned to this action in the subject line on the first page of your response. You may also provide the name, date, and **Federal Register** citation. II. What Action is the Agency Taking? EPA has received a pesticide petition as follows proposing the establishment and/or amendment of regulations for residues of a certain pesticide chemical in or on various food commodities under section 408 of the Federal Food, Drug, and Comestic Act (FFDCA), 21 U.S.C. 346a. EPA has determined that this petition contains data or information regarding the elements set forth in section 408(d)(2); however, EPA has not fully evaluated the sufficiency of the submitted data at this time or whether the data support granting of the petition. Additional data may be needed before EPA rules on the petition. List of Subjects Environmental protection, Agricultural commodities, Feed additives, Food additives, Pesticides and pests, Reporting and recordkeeping requirements. Dated: July 13, 2001. James Jones, Director, Registration Division, Office of Pesticide Programs. Summary of Petition The petitioner summary of the pesticide petition is printed below as required by section 408(d)(3) of the FFDCA. The summary of the petition was prepared by the petitioner and represents the view of the petitioners. EPA is publishing the petition summary verbatim without editing it in any way. The petition summary announces the availability of a description of the analytical methods available to EPA for the detection and measurement of the pesticide chemical residues or an explanation of why no such method is needed. E.I. duPont de Nemours PP7E4847 EPA has received a pesticide petition (PP7E4847) from E.I. duPont de Nemours and Company (Dupont, P.O. Box 80038, Wilmington, DE 19880-0038 proposing, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180 by establishing a tolerance for residues of famoxadone in or on the raw agricultural commodity grapes at 2.0 parts per million and raisins at 4 parts per million (ppm). EPA has determined that the 4 ppm petition contains data or information regarding the elements set forth in section 408(d)(2) of the FFDCA; however, EPA has not fully evaluated the sufficiency of the submitted data at this time or whether the data supports granting of the petition. Additional data may be needed before EPA rules on the petition. A. Residue Chemistry 1. *Plant metabolism* . The plant metabolism of famoxadone is adequately understood in three distinct crops to support these tolerances: Tomatoes, potatoes and grapes. These studies showed no significant metabolites (all < 10%TRR) in the raw agricultural commodities (tubers,tomato fruit, grape berries). The only significant residue in any of the studies was the parent compound, famoxadone, occurring primarily as surface residues (grape berries and tomato fruit). No residues were detected in potato tubers. Thus, the proposed tolerance expression is for the parent compound, famoxadone (DPX-JE874) only. 2. *Analytical method* . An analytical enforcement method is available for determining famoxadone plant residues in or on grapes, raisins, potatoes, cucurbit vegetables (cucumbers, melons and squash), fruiting vegetables (tomatoes, peppers), and head lettuce using gas-liquid chromatography
(GC)with nitrogen phosphorus detection (NPD). The method is applicable to high and medium moisture, oily and non-oily crops and related matrices. The limit of quantitation is 0.02 ppm. The limit of quantitation allows monitoring of crops with famoxadone residues at or above the levels proposed in these tolerances. 3. *Magnitude of residues* — *grapes and raisins.* Results from magnitude of residue and residue decline studies conducted on grapes in major European producing and exporting regions support the grape tolerance of 2.0 ppm. The mean residue value was 0.61 ppm +/− 0.38 ppm with a range of 0.07 to 2.14 ppm. No residues were detected in juice or wine fractions upon processing or fermentation of grapes treated with exaggerated rates of famoxadone. The limit of quantitation was 0.02 ppm. Residues did concentrate by a factor of 1.9X in raisins, thus supporting a tolerance of 4.0 ppm. B. Toxicological Profile 1. *Acute toxicity* . A battery of acute toxicity tests with technical famoxadone places it in the following Toxicity Categories: Study Type Species Results Toixcity Category Oral LD <sup>50</sup> Rat > 5,000 mg/kg Category IV Dermal LD <sup>50</sup> Rabbit > 2,000 mg/kg Category III Inhalation LC <sup>50</sup> Rat > 5.3 mg/L Category IV Eye irritation Rabbit Transient redness; clear by 72 hours Category III Dermal irritation Rabbit Minimal irritation at 72 hours Category IV Dermal sensitization Guinea pig Not a sensitizer In an acute neurotoxicity test, famoxadone was not neurotoxic to rats. The NOAEL was 1,000 milligams/kilogram (mg/kg) in males, based on systemic toxicity at 2,000 mg/kg. The NOAEL in females was 2,000 mg/kg, the highest dose tested (HDT). 2. *Genotoxicity* . Famoxadone was tested in a battery of assays to evaluate genotoxicity and chromosome aberrations with the following results. Based on the weight-of-evidence, famoxadone is not considered to be genotoxic or clastogenic. Bacterial genemutation *Salmonella* and *E. Coli* Negative Mammalian gene mutation *in vitro* CHO/HGPRT Negative Mammalian chromosome aberrations *in vitro* CHO Positive without activation Negative with activation Mammalian chromosome aberrations *in vivo* Mouse micronucleus Negative Unscheduled DNA synthesis *in vitro* Primary rat hepatocytes Negative Unscheduled DNA synthesis *in vivo* Primary rat hepatocytes Negative 3. *Reproductive and developmental toxicity* . The results of a series of studies indicated that there were no reproductive, developmental or teratogenic hazards associated with famoxadone. In a 2-generation rat reproduction study, the NOAEL for both adults and offspring was 200 ppm (11.3-17.5 mg/kg/day depending on gender and generation) based on clinical signs, decreased body weights, effects on nutritional parameters, and liver toxicity in adults and decreased weight of pups. Effects on pups occurred only at a maternal effect level and may have been due to altered growth and nutrition in the dams. There were no effects on reproduction (mating, fertility, and reproductive organs) up to and including the highest concentration tested, 800 ppm (44.7-71.8 mg/kg/day). In studies conducted to evaluate developmental toxicity potential, famoxadone was neither teratogenic nor uniquely toxic to the conceptus. In a rat developmental toxicity study, the maternal NOAEL was 250 mg/kg/day based on decreased weight gain and food consumption at 500 mg/kg/day. The fetal NOAEL was 1,000 mg/kg/day, the HDT. In rabbits, NOAEL for compound-related systemic toxicity was 1,000 mg/kg/day. There were no developmental effects at any dose level. Several rabbits had weight loss, decreased food consumption, clinical signs, fecal impactions and subsequent abortion at 1,000 mg/kg/day. These effects were considered due to the physical properties of the dosing solution rather than systemic toxicity. Often fecal impaction preceded abortions. 4. *Subchronic toxicity* . Subchronic (90-day) feeding studies were conducted with rats, mice, and dogs. In addition, the following subchronic feeding studies were conducted: A 90-day in rats to evaluate neurotoxicity and 28-day feeding studies in rats and mice to evaluate immunotoxicity. A 28-day dermal study was conducted in rats. In a 90-day feeding study in rats, the NOAEL was considered to be 200 ppm (13 and 17 mg/kg/day) based on mild hepatotoxicity and mild regenerative hemolytic anemia in both sexes and decreased body weight in females at 800 ppm (52 and 66 mg/kg/day, in males and females respectively) and higher. An effect on weight gain in female rats at 17 mg/kg/day was considered spurious since it was not duplicated in any other rat studies including those of the same or longer duration. In a subchronic neurotoxicity study in rats, there was no evidence of neurotoxicity up to and including the highest concentration tested, 800 ppm (46.9 and 59.3 mg/kg/day for males and females, respectively). The NOAEL for systemic toxicity was 200 ppm (11.7 and 14.4 mg/kg/day in males and females, respectively) based on body weight and nutritional effects at 800 ppm. In mice, the subchronic NOAEL was 350 ppm (62.4 and 79.4 mg/kg/day in males and females, respectively), based on hepatotoxicity and mild anemic effects at higher concentrations. In a 90-day feeding study in dogs, the NOAEL was 40 ppm (1.3 mg/kg/day) in males. In females, 40 ppm (1.4 mg/kg/day) was a marginal effect level for lens lesions. At 300 ppm, lens lesions were observed in males and females upon ophthalmologic exam and confirmed by histopathology. These lesions were not considered relevant to human health and to acute risk assessment, since they did not occur in a 1-year primate study. Excluding lens lesions, the NOAEL was 300 ppm (10.0 and 10.1 mg/kg/day in males and females, respectively), based upon effects on body weight and food consumption, hemolytic anemia, and hyperkalemia with associated clinical signs at 1000/600 ppm (23.8/21.2 and 23.3/20.1 mg/kg/day in males and females, respectively). The test concentration was lowered to 600 ppm after 5.3 weeks because of the signs related to hyperkalemia. Famoxadone was tested in 28-day feeding studies in rats and mice, designed to evaluate immunotoxicity. The NOAEL in rats was 200 ppm (14 and 16 mg/kg/day in males and females, respectively) based on decreased body weight, body weight gain, food consumption, food efficiency, and increased spleen weights at 800 ppm (55 and 57 mg/kg/day for male and females, respectively). There was no effect in response to sheep red blood cell
(SRBC)challenge at any concentration tested. In mice, the NOAEL was 2,000 ppm (327 and 417 mg/kg/day in males and females, respectively) based onincreased spleen weights and a minimal decrease in humoral response to SRBC. Famoxadone is not considered immunotoxic in rats and produced equivocal evidence of immunotoxicity in mice. In a 28-day repeated dose dermal study, the NOAEL for male rates was 250 mg/kg/day based on changes in liver enzymes at 500 mg/kg/day. The NOAEL for female rats was 1,000 mg/kg/day, the HDT. 5. *Chronic toxicity* . Chronic studies with famoxadone were conducted on rats, mice, dogs and monkeys to determine oncogenic potential and/or chronic toxicity of the compound. Effects generally similar to those observed in the 90-day studies were seen in the chronic studies. Famoxadone was not oncogenic. Famoxadone was not oncogenic in rats. The chronic NOAEL was 200 ppm (8.4 and 10.7 mg/kg/day in males and females, respectively) based on hepatotoxicity and anemia in both sexes and decreased body weight, body weight gain, and food efficiency in females at 400 ppm (16.8 and 23.0 mg/kg/day in males and females, respectively). In mice, the chronic NOAEL was 700 ppm (95.6 and 130 mg/kg/day for males and females, respectively) based on hepatotoxicity in males and females and amyloidosis in females at 2,000 ppm (274 and 392 mg/kg/day in males and females, respectively). Famoxadone was not oncogenic in mice. In a 1-year feeding study in dogs, the only effect observed was lens lesions at 300 ppm (8.8 and 9.3 mg/kg/day for males and females). The NOAEL for these lesions was 40 ppm (1.2 mg/kg/day in both sexes). Use of this NOAEL is considered very conservative since these lesions are not considered appropriate to human risk assessment based on the absence of this effect in a primate study. In a 1-year gavage study, the NOAEL in cynomolgus monkeys was 100 mg/kg/day in both males and female based on slight hemolytic anemia in both sexes at the 1,000 mg/kg/day dose level. There were no other effects observed at any level. 6. *Animal metabolism* . Famoxadone was rapidly eliminated in the rat, primarily by fecal excretion and to a lesser extent in the urine. Absorption and metabolism of famoxadone was limited. There was no accumulation in organs or tissues. Parent famoxadone was the major component recovered. Hydroxylated parent compound and sulfated cleavage products were also recovered to a much lesser extent. 7. *Metabolite toxicology* . There are no metabolites of toxicological significance to mammals. 8. *Endocrine disruption* . Chronic, lifespan, and multigenerational bioassays in mammals and acute and subchronic studies on aquatic organisms and wildlife did not reveal endocrine effects. Any endocrine related effects would have been detected in this definitive array of required tests. The probability of any such effect due to agricultural uses of famoxadone is negligible. C. Aggregate Exposure 1. *Dietary exposure* . Famoxadone is a new fungicide with proposed uses on the commercial crops: Fruiting vegetables (tomatoes and peppers), cucurbit vegetables (cucumbers, melons and squash), head lettuce, potatoes and imported grapes. There are no residential uses for the famoxadone-containing fungicide. i. *Food* . The chronic RfD of 0.012 mg/kg/day is based on a NOAEL of 1.2 mg/kg/day for lens lesions from a 1-year dog feeding study and an uncertainty factor of 100. This is considered highly conservative because these lesions were not produced in a chronic monkey study. The acute NOAEL of 10.0 mg/kg bw/day is based upon body weight effects occurring early in a 90-day dog study. Since body weight is not actually an acute effect, the acute NOAEL selected is highly conservative and it is likely that the actual acute NOAEL is much higher than 10.0 mg/kg/day. a. *Chronic dietary exposure assessment* . Chronic dietary exposure, resulting from all of the proposed uses of famoxadone, cucurbit vegetables, fruiting vegetables, head lettuce, potatoes, and imported grapes, is well within acceptable limits for all sectors of the population. The Chronic Module of the Dietary Exposure Evaluation Model (DEEM, Novigen Sciences, Inc., 1998 Version 6.4 (chronic) and 6.54 (acute)) was used to conduct the assessment with the anticipated reference dose
(RfD)of 0.012 mg/kg/day. The analysis employed overall-mean field-trial values and conservatively assumed that 30% of the crops on the proposed label plus imported grapes would be treated with famoxadone. For the general U.S. population, the estimated chronic dietary exposure to famoxadone is 0.000335 mg/kg/day, and utilizes 2.8% of the chronic RfD. The exposure for the potentially most highly exposed subgroup in the population, children 1-6 years, is 0.000487 mg/kg/day or 4.1% of the chronic RfD. The table below lists the results of this analysis, which indicate large margins of exposure for each population subgroup and very low probability of effects resulting from chronic exposure to famoxadone. Since the RfDs are well below 100%, the chronic dietary safety of famoxadone clearly meets the FQPA standard of reasonable certainty of no harm. **Results of Chronic Dietary Exposure Estimate** Population Group Maximum Dietary Exposure (mg/kg/day) % RfD U.S. Population 0.000335 2.8 Non-Nursing Infants ( < 1 year) 0.000111 0.9 Children (1-6 years) 0.000487 4.1 Children (7-12 years) 0.000391 3.3 Females (13+ years) 0.000430 3.6 b. *Acute dietary exposure* . The acute dietary exposure to famoxadone (99th percentile) is 0.001848 mg/kg/day, or 1.85% acute RfD for the overall U.S. population. The exposure (99th percentile) of the most highly exposed subgroup in the population, children 1-6 years, is 0.002559 mg/kg/day or 2.56% aRfD. The results of this analysis are given in the table below. All of the results are extremely reassuring, because they are based on several very conservative assumptions. Foods that were considered in exposure estimates were cucurbit vegetables, fruiting vegetables, head lettuce, imported grapes, and potatoes. Since the% aRfDs are well below 100%, the acute dietary safety of famoxadone clearly meets the FQPA standard of reasonable certainty of no harm. **Results of Acute Dietary Exposure Estimate** Population group 99TH Percentile of expsure Exposure (mg/kg/day) % RfD 99.9TH Percentile of expsure Exposure (mg/kg/day) % RfD U.S. Population 0.001848 1.85 0.006128 6.13 Non-Nursing ( < 1 year) 0.000949 0.95 0.003667 3.67 Children (1-6 years) 0.002559 2.56 0.008944 8.94 Children (7-12 years) 0.002002 2.00 0.007364 7.36 Females (13-50 years) 0.001843 1.84 0.006072 6.07 ii. *Drinking water* . Famoxadone is highly unlikely to contaminate groundwater resources due to its immobility in soil, low water solubility, high soil sorption, moderate soil half-life, and resulting low ground and surface water exposure. Both acute and chronic drinking water exposure analyses were calculated using EPA screening models (SCI-GROW for groundwater and GENEEC for surface water). Results indicate that a reasonable certainty exists that famoxadone residues will not contribute significantly to the aggregate acute and chronic human risk. The predicted concentration for famoxadone in groundwater under worst case conditions was 0.0097 parts per billion (ppb). The predicted peak concentration for famoxadone in surface water in a small non-flowing pond, directly adjacent to treated fields (aerial application at the maximum rate), was 2.49 ppb. The 56-day average concentration predicted for the same pond scenario was 0.05 ppb. The EPA uses drinking water levels of comparison (DWLOCS) as a surrogate measure to capture risk associated with exposure to pesticides in drinking water. The DWLOC is the concentration of a pesticide in drinking water that would be acceptable as an upper limit in light of total aggregate exposure to that pesticide from food, water and residential uses. A DWLOC will vary depending on the residue level in foods, the toxicity endpoint, drinking water consumption patterns, and body weights for specific subpopulations. The chronic DWLOCs are 0.41 ppm for the U.S. population and 0.12 ppm for the most exposed population subgroup, children (1-6 years). The DWLOCs are substantially higher than the GENEEC 56-day estimated environmental concentration of 0.05 ppb for famoxadone in surface water or the Sci-Grow estimate of 0.0097 ppb famoxadone in ground water. Therefore, since the estimated famoxadone concentrations are well below the chronic DWLOCs, the chronic dietary safety of famoxadone residues from drinking water clearly meets the FQPA standard of reasonable certainty of no harm. Using the appropriate inputs, the acute DWLOCs are 3.3 parts per million
(ppm)for the U.S. population, and 0.91 ppm for the most exposed population subgroup, children (1-6 years). The estimated maximum concentration of famoxadone in surface water (2.49 ppb, derived from GENEEC) or in groundwater (0.0097 ppb, derived from Sci-Grow) is much lower than the acute DWLOC. Since the estimated famoxadone concentrations in ground and surface water are well below acute DWLOCs, the acute dietary safety of famoxadone residues from drinking water clearly meets the FQPA standard of reasonable certainty of no harm. 2. *Non-dietary exposure* . Famoxadone products are not labeled for residential non-food uses, thereby eliminating the potential for residential exposure. Non-occupational, non-dietary exposure for famoxadone has not been estimated because the proposed products are limited to commercial crop production. Therefore, the potential for non-occupational exposure is insignificant. D. Cumulative Effects EPA's consideration of a common mechanism of toxicity is not necessary at this time because there is no indication that toxic effects of famoxadone should be cumulative with those of any other chemical. Famoxadone is a member of a new class of fungicides that acts by inhibition of mitochondrial respiration. Famoxadone's biochemical mode of action on fungi and toxicological profile in animals appear to be unique. Given the distinct chemical, biological and toxicological profile, famoxadone's low acute toxicity, absence of genotoxic, oncogenic, developmental or reproductive effects and low exposure potential, the expression of cumulative human health effects with any other natural or synthetic pesticide is not anticipated. E. Safety Determination 1. *U.S. population* . Dietary and occupational exposure will be the major routes of exposure to the U.S. population. Ample margins of safety have been demonstrated for both situations. For the U.S. population, the chronic dietary exposure to famoxadone from all proposed uses is 0.000335 mg/kg/day, which utilizes 2.8% of the RfD for the overall U.S. population, assuming 30% of the crops are treated. The acute dietary exposure to the U.S. population is 0.001848 mg/kg/day (99th percentile) or 1.85% of the aRFD (99th percentile). At the 99th percentile, the acute dietary exposure for the U.S. population is 0.006128 mg/kg/day or 6.13% of the aRfD. Using only PHED data levels A and B (those with a high level of confidence), the margin of exposures
(MOEs)for occupational exposure are 2,665 to 5,329 for mixer/loaders, 34,418 for aerial applicators, and 1,096 for ground applicators. For flaggers, the MOE is 13,500. Based on the completeness and reliability of the toxicity data and the conservative exposure assessments, there is a reasonable certainty that no harm will result from the aggregate exposure of residues of famoxadone including all anticipated dietary exposure and all other non-occupational exposures. 2. *Infants and children* . Chronic dietary exposure of the most highly exposed subgroup in the population, children 1-6, is 0.000487 mg/kg/day or 4.1% of the RfD. The acute dietary exposure of the most exposed subgroup, children 1-6, is 2.56% of the aRfD (99th percentile). For non-nursing infants ( < 1 year), the acute dietary exposure is 0.95% RfD (99th percentile). There are no residential uses of famoxadone and contamination of drinking water is extremely unlikely. Based on the completeness and reliability of the toxicity data, the lack of toxicological endpoints of special concern, the lack of any indication of greater sensitivity of children, and the conservative exposure assessment, there is a reasonable certainty that no harm will result to infants and children from the aggregate exposure to residues of famoxadone from all anticipated sources of dietary and non-occupational exposure. Accordingly, there is no need to apply an additional safety factor for infants and children. F. International Tolerances To date, no Codex, Canadian, or Mexican tolerances exist for famoxadone. [FR Doc.01-19169 File7-31-01;8:45 am] BILLING CODE 6560-50-S ENVIRONMENTAL PROTECTION AGENCY [OPP-00723; FRL-6787-4] Combined Chronic Toxicity/Carcinogenicity Testing of Respirable Fibrous Particle Final Test Guideline; Notice of Availability AGENCY: Environmental Protection Agency (EPA). ACTION: Notice of availability. SUMMARY: EPA has established a unified library for test guidelines issued by the Office of Prevention, Pesticides and Toxic Substances (OPPTS) for use in testing chemical substances to develop data for submission to EPA under the Toxic Substances Control Act (TSCA), the Federal Food, Drug, and Cosmetic Act (FFDCA), or the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). These test guidelines represent an Agency effort that began in 1991 to harmonize the test guidelines within OPPTS, as well as to harmonize the OPPTS test guidelines with those of the Organization for Economic Cooperation and Development (OECD). The process for developing and amending these test guidelines includes public participation and the extensive involvement of the scientific community, including peer review by the Scientific Advisory Panel
(SAP)and the Scientific Advisory Board
(SAB)and other expert scientific organizations. With this notice, EPA is announcing the availability of the final test guideline for OPPTS 870.8355 Combined Chronic Toxicity/Carcinogenicity Testing of Respirable Fibrous Particles. FOR FURTHER INFORMATION CONTACT: Barbara Cunningham, Director, Office of Program Management and Evaluation, Office of Pollution Prevention and Toxics (7401), Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460; telephone number:
(202)554-1404; e-mail address: TSCA-Hotline@epa.gov. SUPPLEMENTARY INFORMATION: I. Does this Action Apply to Me? This action is directed to the public in general. Although this action may be of particular interest to those persons who are or may be required to conduct testing of chemical substances under TSCA, FFDCA, or FIFRA, the Agency has not attempted to describe all the specific entities that may be affected by this action. If you have any questions regarding the applicability of this action to a particular entity, consult the person under FOR FURTHER INFORMATION CONTACT . II. How Can I Get Additional Information, Including Copies of this Document or Other Related Documents? 1. *Electronically* . You may obtain electronic copies of this document, and certain other related documents that might be available electronically, from the EPA Internet Home Page at http://www.epa.gov/. To access this document, on the Home Page select “Laws and Regulations,” “Regulations and Proposed Rules,” and then look up the entry for this document under the “ **Federal Register** —Environmental Documents.” You can also go directly to the **Federal Register** listings at http://www.epa.gov/fedrgstr/. You may also obtain copies of test guidelines from the EPA Internet Home Page at http://www.epa.gov/opptsfrs/home/guidelin.htm. 2. *In person* . The Agency has established an official record for this final guideline under docket control number OPP-00723. The official record consists of the documents specifically referenced in this action, any public comments received during an applicable comment period, and other information related to this action, including any information claimed as confidential business information (CBI). This official record includes the documents that are physically located in the docket, as well as the documents that are referenced in those documents. The public version of the official record does not include any information claimed as CBI. The public version of the official record, which includes printed, paper versions of any electronic comments submitted during an applicable comment period, is available for inspection in the Public Information and Records Integrity Branch (PIRIB), Rm.119, Crystal Mall #2, 1921 Jefferson Davis Hwy., Arlington, VA, from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The PIRIB telephone number is
(703)305-5805. III. What Action is EPA Taking? EPA is announcing the availability of the final test guideline for OPPTS 870.8355 Combined Chronic Toxicity/Carcinogenicity Testing of Respirable Fibrous Particles. EPA recognizes that the current health effects test guidelines for chronic inhalation toxicity and/or carcinogenicity studies on chemicals are not specific enough for the testing of fibrous substances. These guidelines have to be modified to take into account testing issues which are unique to fibrous particles. Although a number of test systems and/or protocols have been utilized by the scientific community for evaluating the fibrogenic and carcinogenic potential of fibrous particles, there has been considerable debate about the scientific validity and utility of available test methods. Thus, there is a need for EPA to develop a standardized health effects test guideline for fibrous substances that can be used by EPA in future rulemaking, negotiated enforceable consent agreements, or voluntary action to obtain the necessary toxicologic information for risk assessment purposes. The objective of this combined chronic toxicity/carcinogenicity testing of respirable fibrous particles is to determine the effects of a fibrous substance identified to be of potential health concern in at least a rodent species following prolonged and repeated inhalation exposure. The application of this guideline should generate data which identify the majority of chronic toxic and carcinogenic effects and determine dose-response relationships. EPA recognizes concerns have been expressed about data development using animal models. While no comments were received from the animal advocacy community, it is important to note that EPA is committed to avoiding unnecessary or duplicative animal testing. As part of this commitment, the Agency plays an important role in the Federal Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) (http://iccvam.niehs.nih.gov/ home.htm) whose goals are:
(1)To encourage the reduction of the number of animals used in testing;
(2)to seek opportunities to replace test methods requiring animals with alternative test methods when acceptable alternative methods are available; and
(3)to refine existing test methods to optimize animal use when there is no substitute for animal testing. Further, where testing is needed to develop scientifically adequate data, the Agency is committed to reducing the number of animals used for testing, including, whenever possible, by incorporating *in vitro* (non-animal) test methods or other alternative approaches that have been scientifically validated and have received regulatory acceptance. EPA considers these goals and commitments to be important considerations in developing health effects data; however, they must be balanced with the essential need to conduct scientifically sound chemical hazard/risk assessments in support of the Agency's mission to protect human health and the environment studies. IV. Response to Public Comments In the notice of availability for the proposed test guideline published in the **Federal Register** of July 28, 1999 (64 FR 40871) (FRL-6078-6), EPA requested comments from the public on the proposed test guideline which was developed using the current EPA/OPPTS health effects test guideline for combined chronic toxicity and carcinogenicity (Ref. 1) as a template and based on the comments and recommendations made by a 1995 Workshop Panel on a number of scientific issues specific for fiber testing (Refs. 2 and 4). A number of comments on various issues related to the test substance and the study design were received from three U.S. fiber manufacturer associations, a European fiber industry association, a U.S. Government agency, a U.S. consultant, and a European scientist. All public comments were evaluated and a revised draft guideline with some of the public comments incorporated was prepared. At an EPA FIFRA SAP meeting on September 26, 2000, the draft guideline as well as a number of issues raised by the public commenters were reviewed and evaluated by the SAP. In addition to providing EPA with comments on the draft guideline, the SAP provided EPA an opinion on a number of issues raised by the public commenters (Ref. 3). Following are the major public comments received and EPA's responses to these comments. *Comment 1* . A number of commenters expressed that with the recent development of short-term *in vitro* and *in vivo* assay systems for predicting the biopersistence and toxicity of fibers, it is frequently possible to make informed statements about the likely hazard and risk posed by a fiber. Therefore, EPA should make use of these new developments and consider a tiered testing approach; the circumstances under which long-term rodent inhalation studies of a fiber are required should be specified in the guideline. *Response* . In the 1995 Workshop, the panel had identified a number of *in vitro* and *in vivo* short-term screening tests that could be used to develop a minimum data set for making decisions about the potential health hazards of fibers and for prioritizing the need for further testing in a chronic inhalation study. EPA is aware of the recent development of short-term *in vitro* and *in vivo* assay systems for predicting the biopersistence and toxicity of fibers and has initiated a plan to develop a tiered testing approach for identifying potential hazardous fibers for long-term inhalation studies. In response to this comment, the following statement indicating the use of short-term tests to identify potential hazardous fibers for long-term inhalation studies has been added in the “Purpose” paragraph of the guideline: “The fibrous substances to be tested under this guideline will be selected based on data from appropriate short-term screening tests indicative of potential health hazard and risk concern.” *Comment 2* . A commenter indicated that there are no verified reports showing evidence of serious adverse health effects caused by organic fibers in either occupational or consumer settings and suggested that EPA should expressly exclude organic fibers from the guideline. *Response* . As indicated in the response to comment 1, a fibrous substance will be tested for chronic toxicity/carcinogenicity under this guideline only if it is identified to be of potential human health concern. The SAP believed that the guideline will have application to testing of some organic fibers. Since the guideline was derived primarily from experience with inorganic fibers and there are differences between organic and inorganic fibers, the following statement has been added to the test guideline as recommended by the SAP: “While the guideline will have application to testing of organic fibers, additional considerations may be necessary for study of organic fibers.” *Comment 3* . A couple of commenters expressed that it would be very inefficient for the industry to have to conduct more than one study in order to satisfy regulatory guidelines in both Europe and the United States and suggested that EPA should work closely with the Organization for Economic Cooperation and Development
(OECD)to develop a harmonized testing guideline for the chronic toxicity and carcinogenicity of fibers. *Response* . The EPA fiber testing guideline was developed based largely on the recommendations made by a panel of international experts. There are fundamental differences in the purpose and objective of long-term toxicity tests in Europe and the United States. In Europe, the primary purpose of the tests is to collect data for hazard identification while the United States requires the data for both hazard identification and dose-response assessment. Nonetheless, in the development of the EPA fiber testing guideline, attempts have been made to harmonize with available OECD guidelines to the extent possible. *Comment 4* . This comment deals with the definition and criteria of test materials suitable for rat inhalation studies. The guideline specifies that for rat inhalation studies, the fiber samples used should be rat-respirable. A rat-respirable fiber is defined as a fiber with an aspect ratio of at least 3:1 and an aerodynamic diameter of less than 3 μ m. A comment suggested that the definition of a “rat-respirable fiber” should be modified to be “a fiber with a geometric mean diameter
(GMD)≤ 0.8 μ m” since actual measurement of the aerodynamic diameter of fibrous materials by traditional sampling techniques is not always reliable. *Response* . The definition of fibers is adopted from the recommendation of a Workshop Panel and is widely accepted in the field. The Workshop Panel recommended that respirability should be defined on the basis of experimental data, rather than calculated data. For many types of fibers, what reaches the rat lung has been well characterized; an upper limit of 3 μ m aerodynamic diameter is deemed effective in capturing rat-respirable fibers. The guideline defines a “rat-respirable fiber” using the aerodynamic diameter rather than the geometric diameter because the aerodynamic diameter (and not the geometric diameter) is the major determinant for the respirability of fibrous particles. The SAP also concluded that a definition of “rat-respirable fiber” as having an aerodynamic diameter of 3 μ m would be preferable to a definition of GMD of ≤ 0.8 μ m. *Comment 5* . In the definition section of the guideline, the “concentration” of fibrous particles was expressed as the absolute number of fibers/cc. A comment suggested that “Aerosol concentration should also be expressed as the total number of WHO f/cc.” A WHO (World Health Organization) fiber is a fiber with a diameter < 3 μ m and a length > 5 μ m. *Response* . On this issue, the SAP concluded that the definition of concentration of fibrous particles should start with the absolute number of fibers/cc. However, it emphasized that exposure concentrations should also be expressed as WHO fibers/cc as well as fibers greater than 20 μ m/cc and smaller size categories. Accordingly, the following statement has been added into this final test guideline: “Exposure concentrations should also be expressed by fiber length, e.g., WHO fibers (greater than 5 μ m in length)/cc, fibers with length greater than 10, 15 and 20 μ m/cc. *Comment 6* . There are a couple of comments on the selection of animal species for fiber testings. A commenter expressed that the rat inhalation model is not sensitive enough to reliably predict the cancer risk of fibers for human. The basis of the argument is that to cause similar risks from asbestos by chronic inhalation experiments with rats, the fiber concentration per milliliter
(mL)measured with the same method as in the workplace atmosphere has to be about 100 times higher. Another commenter felt that although the hamster is capable of maximizing the number of mesotheliomas that may be induced by a fiber, the cost of such information outweighs its usefulness, and that the use of the model is controversial because hamsters are unusually sensitive to the development of mesothelioma. *Response* . The rat bioassay model has proven to be a fairly good predictor of carcinogenic potential of fibers in humans. Both the Workshop Panel and the SAP concluded that for identifying the carcinogenic potential of fibers via the inhalation route, the rat is clearly the species of choice because of its susceptibility to fiber-induced pulmonary fibrosis, lung neoplasms and mesothelioma. While the rat model is quite effective at identifying the carcinogenic potential of fibers, as the commenter pointed out, it is of less value as a measure of carcinogenic potency. EPA uses testing not only for qualitative determination of carcinogenic potential, but also for quantitative risk assessment, and has historically required the use of two species. Although only the rat model has a sufficient database to be recommended for inhalation exposure studies with fibers, both the Workshop Panel and the SAP expressed that the hamster could be used if mesothelioma was the endpoint of interest because the hamster is more sensitive than the rat for this endpoint. However, the panels commented that the use of the hamster should not be a mandatory requirement because the hamster does not seem to develop lung tumors and lifetime hamster studies are fraught with technical problems. Hence, regarding animal species selection, the final test guideline recommends the rat to be the first species used and since the hamster is more sensitive than the rat with respect of fiber-induced mesothelioma, the hamster should be considered as a second species when results of the rat study show pleural toxicity or neoplasms and dose response data are needed for risk assessment purposes. *Comment 7* . A number of commenters expressed opinions that: “The use of both sexes of rats does not appear warranted, either in expense or the use of additional animals; male and female rats do not appear to differ in their response to the pathogenic effects of fibers.” *Response* . It is true that presently, there is no evidence of a sex difference in response to inhaled fibers, in contrast to non-fibrous particles where female rats appear to be more sensitive (thus a single sex is adequate). As a commenter of the previous comment (comment 6) pointed out, the rat appears to be less sensitive than the human (with regard to tumorigenesis of asbestos), and this provides another reason for using both sexes since the use of both sexes would increase the total number of animals (typically from 50 to 100) and thus the sensitivity of the chronic bioassay. On this issue, the Workshop Panel concluded that testing in both sexes should be encouraged. Most of the SAP members also felt that both sexes of rats should be required for the chronic toxicity and carcinogenicity testing of fibers. Therefore, the final guideline maintains that “Equal numbers of animals of each sex should be used at each dose level.” *Comment 8* . There are a few comments on the characterization of the exposure aerosol. For instance, one commenter suggested that: “The system used to generate fibrous aerosols must not cause significant breakage and contamination of the test substance.” Another commenter suggested to change the sizes of fibers required to be enriched in the exposure aerosol fibers to maximize the sensitivity of animal inhalation exposure studies: “An exposure aerosol should be enriched with the following fiber size fractions: rat respirable fibers with an aspect ratio of at least 3:1 and an aerodynamic diameter less than 2.4 μ m, and include an appropriate number of fibers with lengths of at least 15 μ m.” *Response* . The final test guideline has adopted the suggestion from the commenter that “The system used to generate fibrous aerosols must not cause significant breakage and contamination of the test substance.” Further, it specifies that: “During the development of the generating system, fiber/particle size analysis should be performed to establish the stability of aerosol concentrations with respect to fiber size.” With regard to the fibers to be enriched in the exposure aerosol to maximize the sensitivity of animal inhalation exposure studies, the guideline first specifies that the aerosol should be characterized in terms of fiber and non-fiber/particle size and number; the number of fiber should be expressed by fiber length, e.g., WHO fibers (greater than 5 μ m in length), fibers greater than 10, 15 and 20 μ m in length. It is realized that different fiber types may have different size characteristics and it may not always be feasible to generate long, thin fibers (e.g., longer that 20 μ m, thinner than 1 μ m) as was specified in the draft guideline. Therefore, the final test guideline no longer specifies the fiber size requirement and simply states that: “The test material should consist of rat-respirable fibers which should be enriched with the most potent fraction of long, thin fibers or fibers with high aspect ratios. ..... If enriching the test aerosol with long, thin fibers is not feasible, the reasons should be clearly stated and justified, and the enrichment should be for the longest fibers or fibers with the highest aspect ratios available.” *Comment 9* . This comment relates to the selection of the highest fiber concentration level, known as the Maximal Aerosol Concentration or MAC, to be tested in a chronic inhalation exposure study. A commenter expressed concern that while the use of an insufficient number of long fibers would produce false negative results, using too large a mass exposure would cause pulmonary overload and produce false positive results. Therefore, it would be more useful operationally if the word “appropriate” is defined in the guideline: “An appropriate lung burden of critical fibers (long and thin) should be achieved” (for setting the MAC). Another commenter felt that the definition of MAC should be expanded to include the following statement: “The MAC is the highest concentration of test substance that will not cause a significant impairment (retardation) of particle clearance based on assessment of clearance in a 90-day subchronic inhalation study.” *Response* . The final guideline has specified that the MAC, the highest fiber concentration to be tested in a chronic study, should be set at a level at which some degree of impaired clearance and toxicity (as determined by parameters observed during lung burden analysis and bronchoalveolar lavage fluid
(BALF)analysis in a 90-day subchronic inhalation study) are observed. The SAP concluded that there is no universal level of long fibers that would serve as an appropriate lung burden for all types of fibers. Important differences in the biopersistence and other key physicochemical properties account for the difficulty in setting a single appropriate burden. Present information is insufficient to set levels for what constitutes “significant impairment” of particle clearance. Both the Workshop Panel and the SAP concluded that a weight-of-evidence approach, based on all data of the 90-day subchronic inhalation studies, should be used for establishing whether a given exposure meets or exceeds the MAC. *Comment 10* . On fiber concentration level selection, a commenter suggested that “The lower exposures should be defined as some fractions of the highest exposure.” Another commenter expressed that: “A single exposure level would suffice if it is anticipated that the MAC will not show carcinogenic activity.” *Response* . The guideline does not attempt to provide specific fractions/numbers to define the lower exposure levels. The lower levels should be appropriately spaced to produce a gradation of toxic effects. A rationale for the concentrations selected must be provided. The objective of a combined chronic toxicity/carcinogenicity study is to determine the effects of a fibrous substance identified to be of potential health concern. If a fibrous material is not anticipated to have any health hazard concern, a chronic inhalation study need not be performed. When a fibrous substance is to be tested, for dose-response analysis, at least three concentrations levels should be used. *Comment 11* . A commenter expressed that “recovery” animals for satellite dose groups in lung burden analysis and BALF analysis can provide important information on the interpretation of the test results and suggested to remove a minimal of 5 animals from each dose group at 3, 6, 12, and 18 months of exposure and then hold until 24 months at which they will be evaluated for the kinetics of fiber buildup/removal from the lungs and progression/regression of lesions. *Response* . The final guideline has adopted the suggestions of this comment which is endorsed by the SAP. *Comment 12* . A couple of commenters expressed that BALF analysis data are useful in the 90-day studies and are not of any value in the lifetime studies. *Response* . Most members of the SAP felt that BALF analysis at interim time points (3, 6, 12, 18 and 24 months) are very useful for an overall evaluation of the fiber toxicity and proper interpretation of the study results. However, it was also felt that a decision to include all time points should be left to the individual study design, and some of the interim time points (e.g., 3, 6 and 18 months) could be omitted. On the basis of this, the final guideline requires BALF analysis be conducted only at the 12 and 24 month sacrifices and makes other time points optional. *Comment 13* . On clinical pathology (hematology and serum chemistry) and ophthalmology evaluation, there were comments that these determinations provide little toxicological value in the assessment of fiber hazard/risk and should be omitted. *Response* . The final guideline has adopted the suggestions of these comments which are endorsed by the SAP. However, evaluation of these parameters is required when clinical changes are seen in subchronic studies. *Comment 14* . On histopathology, a commenter suggested that: “The histology slides from the scheduled sacrifices should also be stained with Masson-Goldner's trichrome stain that identifies collagen (fibrosis),” and that: “The scheduled sacrifices should be recorded according to the Wagner scoring method.” *Response* . In response to this comment, the following statement has been added into the final test guideline: “The histology slides from the scheduled sacrifices should, in addition to standard hematoxylin and eosin, be stained with a method that identifies collagen (fibrosis).” The SAP commented that there are many stains for collagen and no single stain should be specified. The Wagner scoring system has proved useful for providing a consistent and systemic reference for parenchymal disease. It also can be of value when attempting to compare the pathogenic effects of one fiber to another. However, use of the Wagner scoring system to evaluate progression of fibrosis has the disadvantage of being purely qualitative. The SAP suggested to take a consistent approach to record and grade the findings of airway disease and to use “image analysis” to assess severity of lesions. The recommendations of the SAP were incorporated into the final guideline. V. How Was this Test Guideline Developed? On May 8-10, 1995, a Workshop on chronic inhalation toxicity and carcinogenicity testing of respirable fibrous particles was held in Chapel Hill, North Carolina. The Workshop was sponsored by the Office of Pollution Prevention and Toxics, Environmental Protection Agency, in collaboration with the National Institute of Environmental Health Sciences (NIEHS), the National Institute for Occupational Safety and Health (NIOSH), and the Occupational Safety and Health Administration (OSHA). The goal of the Workshop was to obtain input from the scientific community on a number of issues related to fiber testing. The Workshop Panel, which was composed of 19 international expert scientists in inhalation toxicology, reviewed, evaluated, and commented on the scientific issues of the Workshop. After extensive discussion and debate of the Workshop issues, the Workshop Panel provided a number of recommendations specific for the design and conduct of chronic inhalation studies of fibers (Refs. 2 and 4). Using the current EPA/OPPTS health effects test guideline for combined chronic toxicity and carcinogenicity (Ref. 1) as a template and based on the comments and recommendations made by the Workshop Panel on a number of scientific issues specific for fiber testing, EPA/OPPT developed a proposed guideline for combined chronic toxicity and carcinogenicity testing of fibrous particles. In July 1999, the proposed guideline was announced in the **Federal Register** for public comments (64 FR 40871, July 28, 1999). A number of comments on various issues related to the test substance and study design were received. All public comments were evaluated and a revised draft guideline with some of the public comments incorporated was prepared. On September 26, 2000, the EPA FIFRA SAP held a meeting to review the EPA draft guideline, advise on a number of issues raised by the public commenters on the study protocol, and provide EPA with an opinion about the scientific validity of the test guideline. The final test guideline for OPPTS 870.8355 Combined Chronic Toxicity/ Carcinogenicity Testing of Respirable Fibrous Particles has incorporated many of the comments and recommendations made by the SAP (Ref. 3). VI. Are there Any Applicable Voluntary Consensus Standards that EPA Should Consider? This notice of availability does not involve a proposed regulatory action that would require the Agency to consider voluntary consensus standards pursuant to section 12(d) of the National Technology Transfer and Advancement Act of 1995 (NTTAA), Public Law 104-113, section 12(d) (15 U.S.C. 272 note). Section 12(d) directs EPA to use voluntary consensus standards in its regulatory activities unless to do so would be inconsistent with applicable law or otherwise impractical. Voluntary consensus standards are technical standards (e.g., materials specifications, test methods, sampling procedures, and business practices) that are developed or adopted by voluntary consensus standards bodies. The NTTAA requires EPA to provide an explanation to Congress, through Office of Management and Budget (OMB), when the Agency decides not to use available and applicable voluntary consensus standards when the NTTAA directs the Agency to do so. In the notice of availability for the proposed test guideline published in the **Federal Register** of July 28, 1999 (64 FR 40871), EPA specifically sought comment on the availability of any applicable voluntary consensus standards that should be considered during the development of the final test guideline or any future regulatory action that EPA may take under TSCA. No response to this request was received. VII. References The following references are cited in this document by the number indicated: 1. United States Environmental Protection Agency. Health Effects Test Guidelines: Combined Chronic Toxicity/Oncogenicity. 40 CFR 798.3320. pp. 165-172. 2. United States Environmental Protection Agency. Office of Pollution Prevention and Toxics. Workshop on Chronic Inhalation Toxicity and Carcinogenicity Testing of Respirable Fibrous Partcles. EPA-748-R-96-001, January 1996. 3. United States Environmental Protection Agency. FIFRA Scientific Advisory Panel Meeting on Test Guidelines for Chronic Inhalation Toxicity and Carcinogenicity of Fibrous Partcles, September 26, 2000. SAP Report No. 2000-0X, 01/05/2001. 4. Vu, V., Barrett, J.C., Roycroft, J., Schuman, L., Dankovic, D., Baron, P., Martonen, T., Pepelko, W. and Lai, D. Workshop Report: Chronic Inhalation Toxicity and Carcinogenicity Testing of Respirable Fibrous Particles. Regulatory Toxicology and Pharmacology 24:202-212 (1996). List of Subjects Environmental protection, Chemical testing, Test guideline. Dated: July 17, 2001. Stephen L. Johnson, Assistant Administrator for Prevention, Pesticides and Toxic Substances. [FR Doc. 01-18890 Filed 7-31-01; 8:45 am]
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