# Protection of Stratospheric Ozone: Listing of Substitutes for Ozone-Depleting Substances-n-Propyl Bromide > Briefs, arguments, decisions, and more. URL: https://www.frixlaw.com/law-library/documents/fr%3A03-13254 ## Record - **Collection:** Federal Register - **Document type:** Proposed Rule - **Published:** June 3, 2003 - **Citation:** 68 FR 33284 ## Text ENVIRONMENTAL PROTECTION AGENCY 40 CFR Part 82 [FRL-7504-3] RIN 2060-AK28 Protection of Stratospheric Ozone: Listing of Substitutes for Ozone-Depleting Substances—n-Propyl Bromide AGENCY: Environmental Protection Agency. ACTION: Notice of proposed rulemaking. SUMMARY: This action proposes to list n-propyl bromide (nPB) as an acceptable substitute for ozone-depleting substances (ODSs), subject to use conditions, in the solvent cleaning sector and aerosol solvents and adhesive end uses under the U.S. Environmental Protection Agency's (EPA or “we”) Significant New Alternatives Policy (SNAP) program. The SNAP program implements section 612 of the amended Clean Air Act of 1990 (CAA), which requires EPA to evaluate substitutes for ODSs in order to reduce overall risk to human health and the environment. While we find that nPB has a short atmospheric lifetime and low ozone depletion potential when emitted from locations in the continental U.S., the Agency cautions that significant use of nPB closer to the equator poses significant risks to the stratospheric ozone layer. Further, if workplace exposure to nPB is poorly controlled, it may increase health risks to workers. In the interim, until the Occupational Safety and Health Administration (OSHA) develops a mandatory workplace exposure limit under Section 6 of the Occupational Safety and Health Act, the Agency recommends that users of nPB adhere to an acceptable exposure limit of 25 parts per million (ppm) over an eight-hour time-weighted average. In today's action, EPA proposes that the use of nPB is acceptable subject to a use condition, in a limited number of specific applications where emissions can be tightly controlled for both environmental and exposure concerns. The proposal only allows the use of nPB as a solvent in metals, precision, and electronics cleaning, and in aerosol solvent and adhesive end-uses. EPA is proposing to list nPB as an acceptable substitute for chlorofluorocarbon (CFC)-113, hydrochlorofluorocarbon (HCFC)-141b, and methyl chloroform when used in aerosol solvent and adhesive end uses, subject to the condition that nPB used in these end uses not contain more than 0.05% isopropyl bromide by weight before adding stabilizers or other chemicals. We are also proposing to list nPB as an acceptable substitute for CFC-113 and methyl chloroform in general metals cleaning, electronics cleaning, and precision cleaning, subject to the condition that nPB used in these end uses not contain more than 0.05% isopropyl bromide by weight before adding stabilizers or other chemicals. DATES: Comments must be received in writing by August 4, 2003. ADDRESSES: Comments may be submitted by mail to: Air and Radiation Docket, Environmental Protection Agency, Mailcode 6102T, 1200 Pennsylvania Ave., NW., Washington, DC 20460, Attention Docket ID No. OAR-2002-0064. Comments may also be submitted electronically, by facsimile, or through hand delivery/courier. Follow the detailed instructions as provided at the beginning of the “supplementary information” section. FOR FURTHER INFORMATION CONTACT: For further information about this proposed rule, contact Margaret Sheppard by telephone at (202) 564-9163, or by e-mail at sheppard.margaret@epa.gov. Notices and rulemakings under the SNAP program are available on EPA's Stratospheric Ozone World Wide Web site at http://www.epa.gov/ozone/snap/regs. SUPPLEMENTARY INFORMATION: Table of Contents I. General Information A. Regulated entities B. How can I get copies of related information? C. How and to whom do I submit comments? D. How should I submit CBI to the agency? E. Acronyms and abbreviations used in the preamble II. How does the Significant New Alternatives Policy (SNAP) program work? A. What are the statutory requirements and authority for the SNAP program? B. How do the regulations for the SNAP program work? C. Where can I get additional information about the SNAP program? III. Is EPA listing n-propyl bromide as an acceptable substitute for ozone-depleting substances? A. What is EPA proposing today? B. What is n-propyl bromide? C. What industrial sectors are included in our proposed decision? IV. What did EPA consider in preparing today's proposal? A. Toxicity 1. What Acceptable Exposure Limit is EPA recommending for n-propyl bromide, and why? a. Summary of toxicity studies b. Derivation of an AEL for nPB c. Overview of the Center for Evaluation of Risk to Human Reproduction (CERHR) Expert Panel Report d. AELs suggested by other reviewers and outside parties e. Feasibility of meeting the AEL for nPB in each sector 2. Are there other entities that may set workplace standards for nPB? 3. Is the general population exposed to too much nPB? 4. What limit is EPA setting on isopropyl bromide contamination of n-propyl bromide as a condition of acceptability, and why? B. Ozone depletion potential C. Global warming potential D. Flammability E. Other environmental concerns F. Comparison of nPB to other solvents V. What other factors did EPA consider that are unique to nPB? A. Continued review of nPB by other federal and international programs B. Potential market for n-propyl bromide C. Estimated economic impacts on businesses VI. How is EPA responding to comments on the advance notice of proposed rulemaking and December 18, 2000 notice of data availability? VII. What should I include in my comments on EPA's proposal? VIII. What is the federal government doing to help businesses use nPB safely? IX. How can I use nPB as safely as possible? X. Statutory and Executive Order Reviews XI. References I. General Information A. Regulated Entities Today's proposal would regulate the use of n-propyl bromide as a solvent used in industrial equipment for metals cleaning, electronics cleaning, or precision cleaning, and as an aerosol solvent and a carrier solvent in adhesives. Businesses that currently might be using nPB, or might want to use it in the future, include: • Businesses that clean metal parts, such as automotive manufacturers, machine shops, machinery manufacturers, and electroplaters. • Businesses that manufacture electronics or computer equipment. • Businesses that require a high level of cleanliness in removing oil, grease, or wax, such as for aerospace applications or for manufacture of optical equipment. • Foam fabricators that glue pieces of polyurethane foam together or foam cushion manufacturers that glue fabric around a cushion. • Furniture manufacturers that use adhesive to attach wood parts to floors, tables and counter tops. Regulated entities may include: Table 1.—Potentially Regulated Entities, by North American Industrial Classification System (NAICS) Code or Subsector Category NAICS code or subsector Description of regulated entities Industry 331 Primary metal manufacturing Industry 332 Fabricated metal product manufacturing Industry 333 Machinery manufacturing Industry 334 Computer and electronic product manufacturing Industry 336 Transportation equipment manufacturing Industry 337 Furniture and related product manufacturing Industry 326150 Urethane and other foam product (except polystyrene) manufacturing This table is not intended to be exhaustive, but rather a guide regarding entities likely to be regulated by this action. If you have any questions about whether this action applies to a particular entity, consult the person listed in the preceding section, FOR FURTHER INFORMATION CONTACT. B. How Can I Get Copies of Related Information? 1. Docket EPA has established an official public docket for this action under Docket ID No. OAR-2002-0064 (continuation of Docket A-2001-07). The official public docket consists of the documents specifically referenced in this action, any public comments received, and other information related to this action. Hard copies of documents from prior to the public comment period are found under Docket ID No. A-2001-07. Although a part of the official docket, the public docket does not include Confidential Business Information (CBI) or other information whose disclosure is restricted by statute. The official public docket is the collection of materials that is available for public viewing at the Air and Radiation Docket in the EPA Docket Center, (EPA/DC) EPA West, Room B102, 1301 Constitution Ave., NW., Washington, DC. The EPA Docket Center Public Reading Room is open from 8:30 a.m. to 4:30 p.m., Monday through Friday, excluding legal holidays. The telephone number for the Reading Room is (202) 566-1742, and the telephone number for the Air and Radiation Docket is (202) 566-1742. 2. Electronic Access An electronic version of the public docket is available through EPA's electronic public docket and comment system, EPA Dockets. You may use EPA Dockets at http://www.epa.gov/edocket/ to submit or view public comments, access the index listing of the contents of the official public docket, and to access those documents in the public docket that are available electronically. Once in the system, select “search,” then key in the appropriate docket identification number. Certain types of information will not be placed in the EPA Dockets.Information claimed as CBI and other information whose disclosure is restricted by statute, which is not included in the official public docket, will not be available for public viewing in EPA's electronic public docket. EPA's policy is that copyrighted material will not be placed in EPA's electronic public docket but will be available only in printed, paper form in the official public docket. Although not all docket materials may be available electronically, you may still access any of the publicly available docket materials through the docket facility identified in section I.B.1. above. For public commenters, it is important to note that EPA's policy is that public comments, whether submitted electronically or in paper, will be made available for public viewing in EPA's electronic public docket as EPA receives them and without change, unless the comment contains copyrighted material, CBI, or other information whose disclosure is restricted by statute. When EPA identifies a comment containing copyrighted material, EPA will provide a reference to that material in the version of the comment that is placed in EPA's electronic public docket. The entire printed comment, including the copyrighted material, will be available in the public docket. Public comments submitted on computer disks that are mailed or delivered to the docket will be transferred to EPA's electronic public docket. Public comments that are mailed or delivered to the Docket will be scanned and placed in EPA's electronic public docket. Where practical, physical objects will be photographed, and the photograph will be placed in EPA's electronic public docket along with a brief description written by the docket staff. C. How and to Whom Do I Submit Comments? You may submit comments electronically, by mail, by facsimile, or through hand delivery/courier. To ensure proper receipt by EPA, identify the appropriate docket identification number in the subject line on the first page of your comment. Please ensure that your comments are submitted within the specified comment period. Comments received after the close of the comment period will be marked “late.” EPA is not required to consider these late comments. If you wish to submit CBI or information that is otherwise protected by statute, please follow the instructions in section I.D. Do not use EPA Dockets or e-mail to submit CBI or information protected by statute. 1. Electronically. If you submit an electronic comment as prescribed below, EPA recommends that you include your name, mailing address, and an e-mail address or other contact information in the body of your comment. Also include this contact information on the outside of any disk or CD ROM you submit, and in any cover letter accompanying the disk or CD ROM. This ensures that you can be identified as the submitter of the comment and allows EPA to contact you in case EPA cannot read your comment due to technical difficulties or needs further information on the substance of your comment. EPA's policy is that EPA will not edit your comment, and any identifying or contact information provided in the body of a comment will be included as part of the comment that is placed in the official public docket, and made available in EPA's electronic public docket. If EPA cannot read your comment due to technical difficulties and cannot contact you for clarification, EPA may not be able to consider your comment. Your use of EPA's electronic public docket to submit comments to EPA electronically is EPA's preferred method for receiving comments. Go directly to EPA Dockets at http://www.epa.gov/edocket, and follow the online instructions for submitting comments. To access EPA's electronic public docket from the EPA Internet Home Page, select “Information Sources,” “Dockets,” and “EPA Dockets.” Once in the system, select “search,” and then key in Docket ID No. OAR-2002-0064. The system is an “anonymous access” system, which means EPA will not know your identity, e-mail address, or other contact information unless you provide it in the body of your comment. Comments may be sent by electronic mail (e-mail) to A-And-R- Docket@epa.gov, Attention Docket ID No. OAR-2002-0064. In contrast to EPA's electronic public docket, EPA's e-mail system is not an “anonymous access” system. If you send an e-mail comment directly to the Docket without going through EPA's electronic public docket, EPA's e-mail system automatically captures your e-mail address. E-mail addresses that are automatically captured by EPA's e-mail system are included as part of the comment that is placed in the official public docket, and made available in EPA's electronic public docket. You may submit comments on a disk or CD ROM that you mail to the mailing address identified in section I.B.1. These electronic submissions will be accepted in WordPerfect or ASCII file format. Avoid the use of special characters and any form of encryption. 2. By Mail. Send two copies of your comments to: Air and Radiation Docket, Environmental Protection Agency, Mailcode: 6102T, 1200 Pennsylvania Ave., NW., Washington DC, 20460, Attention: Docket ID No. OAR-2002-0064. 3. By Hand Delivery or Courier. Deliver your comments to: EPA Docket Center, (EPA/DC) EPA West, Room B102, 1301 Constitution Ave., NW., Washington, DC, Attention Docket ID No. OAR-2002-0064. Such deliveries are only accepted during the Docket's normal hours of operation as identified in section I.B.1. 4. By Facsimile. Fax your comments to: 202-566-1741, Attention: Docket ID No. OAR-2002-0064. D. How Should I Submit CBI to the Agency? Do not submit information that you consider to be CBI electronically through EPA's electronic public docket or by e-mail. Send or deliver information identified as CBI only to the following address: Margaret Sheppard, U.S. EPA, 4th floor, 501 3rd Street NW., Washington DC 20001, via delivery service. You may claim information that you submit to EPA as CBI by marking any part or all of that information as CBI (if you submit CBI on disk or CD ROM, mark the outside of the disk or CD ROM as CBI and then identify electronically within the disk or CD ROM the specific information that is 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 docket and EPA's electronic public docket. If you submit the copy that does not contain CBI on disk or CD ROM, mark the outside of the disk or CD ROM clearly that it does not contain CBI. Information not marked as CBI will be included in the public docket and EPA's electronic public docket without prior notice. If you have any questions about CBI or the procedures for claiming CBI, please consult the person identified in the FOR FURTHER INFORMATION CONTACT section. E. Acronyms and Abbreviations Used in the Preamble Below is a list of acronyms and abbreviations used in this document. 1,1,1 —the ozone-depleting chemical 1,1,1-trichloroethane, CAS Reg. No. 71-55-6; also called TCA, methyl chloroform, or MCF 1-BP —the chemical 1-bromopropane, C 3 H 7 Br, CAS Reg. No. 106-94-5; also called n-propyl bromide or nPB 2-BP —the chemical 2-bromopropane, C 3 H 7 Br, CAS Reg. No. 75-26-3; also called isopropyl bromide or iPB 2-D —two-dimensional 3-D —three dimensional ACGIH —American Congress of Governmental Industrial Hygienists AEL —acceptable exposure limit AFEAS —Alternative Flurocarbon Environmental Acceptability Study AIC —Akaike Information Criterion AIHA —American Industrial Hygienists Association ANPRM —Advance Notice of Proposed Rulemaking ASTM —American Society for Testing and Materials BMD —benchmark dose BMDL —benchmark dose lowerbound, the lower 95%-confidence level bound on the dose/exposure associated with the benchmark response BMR —benchmark response BSOC —Brominated Solvents Consortium CAA —Clean Air Act CAS Reg. No. —Chemical Abstracts Service Registry Identification Number CBI —Confidential Business Information CERHR —Center for the Evaluation of Risks to Human Reproduction CFC-113 —the ozone-depleting chemical trifluorotrichloroethane, C 2 Cl 3 F 3 , CAS Reg. No. 76-13-1 CFCs —chlorofluorocarbons CFR —Code of Federal Regulations CNS —Central nervous system EPA —the United States Environmental Protection Agency FR — Federal Register GLP —Good Laboratory Practice GWP —global warming potential HCFC-123 —the ozone-depleting chemical 1,2-dichloro-1,1,2-trifluoroethane, CAS Reg. No. 306-83-2 HCFC-141b —the ozone-depleting chemical 1,1,1-trichloro-2-fluoroethane, CAS Reg. No. 1717-00-6 HCFC-225ca/cb —the commercial mixture of the two ozone-depleting chemicals 3,3-dichloro-1,1,1,2,2-pentafluoro-propane, CAS Reg. No. 422-56-0 and 3,3-dichloro-1,1,2,2,3-pentafluoropropane, CAS Reg. No. 507-55-1 HCFCs —hydrochlorofluorocarbons HEC —human equivalent concentration HESIS —Hazard Evaluation System and Information Service of the California Department of Health Services HFC-245fa —the chemical 1,1,3,3,3-pentafluoropropane, CAS Reg. No. 460-73-1 HFC-365mfc —the chemical 1,1,3,3,3-pentafluorobutane, CAS Reg. No. 405-58-6 HFC-4310mee —the chemical 1,1,1,2,3,4,4,5,5,5-decafluoropentane, CAS Reg. No. 138495-42-8 HFCs —hydrofluorocarbons HFEs —hydrofluoroethers HHE —health hazard evaluation HSIA —Halogenated Solvents Industry Alliance IARC —International Agency for Research on Cancer ICF —ICF Consulting ICR —Information Collection Request iPB —isopropyl bromide, C 3 H 7 Br, CAS Reg. No. 75-26-3, an isomer of n-propyl bromide; also called 2-bromopropane or 2-BP IPCC —International Panel on Climate Change IRTA —Institute for Research and Technical Assistance LOAEL —Lowest Observed Adverse Effect Level MF —modifying factor MSDS —Material Safety Data Sheet NAICS —North American Industrial Classification System NESHAP —National Emission Standards for Hazardous Air Pollutants NIEHS —National Institute of Environmental Health Services NIOSH —National Institute for Occupational Safety and Health NOAEL —No Observed Adverse Effect Level NOEL —No Observed Effect Level nPB —n-propyl bromide, C 3 H 7 Br, CAS Reg. No. 106-94-5; also called 1-bromopropane or 1-BP NPRM —Notice of Proposed Rulemaking NTP —National Toxicology Program NTTAA —National Technology Transfer and Advancement Act ODP —ozone depletion potential ODS —ozone-depleting substance OMB —U.S. Office of Management and Budget OSHA —U.S. Occupational Safety and Health Administration PCBTF —parachlorobenzotrifluoride, CAS Reg. No. 98-56-6 PEL —Permissible Exposure Limit PERC —perchloroethylene, also called tetrachloroethylene; C 2 Cl 4 , CAS Reg. No. 127-18-4 POD —point of departure ppm —parts per million RCRA —Resource Conservation and Recovery Act RFA —Regulatory Flexibility Act RfC —reference concentration RfD —reference dose SBREFA —Small Business Regulatory Enforcement Fairness Act SNAP —Significant New Alternatives Policy STEL —short term exposure limit TCA —the ozone-depleting chemical 1,1,1-trichloroethane, CAS Reg. No. 71-55-6; also called 1,1,1, methyl chloroform, or MCF TCE —trichloroethylene, C 2 Cl 3 H, CAS Reg. No. 79-01-6 TEAP —Technical and Economic Assessment Panel of the United Nations Environmental Programme TSCA —Toxic Substances Control Act TWA —time-weighted average UF —uncertainty factor UMRA —Unfunded Mandates Reform Act UNEP —United Nations Environmental Programme VMSs —volatile methyl siloxanes VOC —volatile organic compound II. How Does the Significant New Alternatives Policy (SNAP) Program Work? A. What Are the Statutory Requirements and Authority for the SNAP Program? Section 612 of the Clean Air Act (CAA) authorizes EPA to develop a program for evaluating alternatives to ozone-depleting substances, referred to as the Significant New Alternatives Policy (SNAP) program. The major provisions of section 612 are: • Rulemaking —Section 612(c) requires EPA to promulgate rules making it unlawful to replace any class I (chlorofluorocarbon, halon, carbon tetrachloride, methyl chloroform, and hydrobromofluorocarbon) or class II (hydrochlorofluorocarbon) substance with any substitute that the Administrator determines may present adverse effects to human health or the environment where the Administrator has identified an alternative that (1) reduces the overall risk to human health and the environment, and (2) is currently or potentially available. • Listing of Unacceptable/Acceptable Substitutes— Section 612(c) also requires EPA to publish a list of the substitutes unacceptable for specific uses. We must publish a corresponding list of acceptable alternatives for specific uses. • Petition Process— Section 612(d) grants the right to any person to petition EPA to add a substitute to or delete a substitute from the lists published in accordance with section 612(c). EPA has 90 days to grant or deny a petition. Where the Agency grants the petition, we must publish the revised lists within an additional six months. • 90-day Notification— Section 612(e) requires EPA to require any person who produces a chemical substitute for a class I substance to notify the Agency not less than 90 days before new or existing chemicals are introduced into interstate commerce for significant new uses as substitutes for a class I substance. The producer must also provide the Agency with the producer's health and safety studies on such substitutes. • Outreach— Section 612(b)(1) states that the Administrator shall seek to maximize the use of federal research facilities and resources to assist users of class I and II substances in identifying and developing alternatives to the use of such substances in key commercial applications. • Clearinghouse— Section 612(b)(4) requires the Agency to set up a public clearinghouse of alternative chemicals, product substitutes, and alternative manufacturing processes that are available for products and manufacturing processes which use class I and II substances. B. How Do the Regulations for the SNAP Program Work? On March 18, 1994, EPA published the original rulemaking (59 FR 13044) that described the process for administering the SNAP program and issued our first acceptability lists for substitutes in the major industrial use sectors. These sectors include: Refrigeration and air conditioning; foam blowing; solvents cleaning; fire suppression and explosion protection; sterilants; aerosols; adhesives, coatings and inks; and tobacco expansion. These sectors comprise the principal industrial sectors that historically consumed large volumes of ozone-depleting substances. Anyone who produces a substitute for an ODS must provide the Agency with health and safety studies on the substitute at least 90 days before introducing it into interstate commerce for significant new use as an alternative. This requirement applies to chemical manufacturers, but may include importers, formulators or end-users when they are responsible for introducing a substitute into commerce. The Agency has identified four possible decision categories for substitutes: acceptable; acceptable subject to use conditions; acceptable subject to narrowed use limits; and unacceptable. Use conditions and narrowed use limits are both considered “use restrictions” and are explained below. Substitutes that are deemed acceptable with no use restrictions (no use conditions or narrowed use limits) can be used for all applications within the relevant sector end-use. Substitutes that are acceptable subject to use restrictions may be used only in accordance with those restrictions. It is illegal to replace an ODS with a substitute listed as unacceptable. After reviewing a substitute, the Agency may make a determination that a substitute is acceptable only if certain conditions of use are met to minimize risks to human health and the environment. We describe such substitutes as “acceptable subject to use conditions.” If you use these substitutes without meeting the associated use conditions, you use these substitutes in an unacceptable manner and you could be subject to enforcement for violation of section 612 of the Clean Air Act. For some substitutes, the Agency may permit a narrowed range of use within a sector (that is, we may limit the use of a substitute to certain end-uses or specific applications within an industry sector), to allow alternatives to be used in specific uses that would otherwise be deemed unacceptable. We describe these substitutes as “acceptable subject to narrowed use limits.” If you use a substitute that is acceptable subject to narrowed use limits, but use it in applications and end-uses which are not specified as acceptable in the narrowed use limit, you are using these substitutes in an unacceptable manner and you could be subject to enforcement for violation of section 612 of the Clean Air Act. The Agency publishes its SNAP program decisions in the Federal Register . For those substitutes that are deemed acceptable subject to use restrictions (use conditions and/or narrowed use limits), or for substitutes deemed unacceptable, we first publish these decisions as proposals to allow the public opportunity to comment, and we publish final decisions as final rulemakings. In contrast, we publish substitutes that are deemed acceptable with no restrictions in “notices of acceptability,” rather than as proposed and final rules. As described in the rule implementing the SNAP program (59 FR 13044), we do not believe that rulemaking procedures are necessary to list alternatives that are acceptable without restrictions because such listings neither impose any sanction nor prevent anyone from using a substitute. Many SNAP listings include “comments” or “further information.” These statements provide additional information on substitutes that we determine are either unacceptable, acceptable subject to narrowed use limits, or acceptable subject to use conditions. Since this additional information is not part of the regulatory decision, you are not required to follow these statements to use a substitute unless they specifically reference regulatory requirements. The further information does not necessarily include all other legal obligations pertaining to the use of the substitute. However, we encourage users of substitutes to apply all statements in the “Further Information” column in their application of these substitutes, regardless of any regulatory requirements. In many instances, the information simply refers to sound operating practices that have already been identified in existing industry and/or building-code standards. Thus, many of the comments, if adopted, would not require the affected industry to make significant changes in existing operating practices. C. Where Can I Get Additional Information About the SNAP Program? For copies of the comprehensive SNAP lists of substitutes or additional information on SNAP, look at EPA's Ozone Depletion World Wide Web site at http://www.epa.gov/ozone/snap/lists/index.html. For more information on the Agency's process for administering the SNAP program or criteria for evaluation of substitutes, refer to the SNAP final rulemaking published in the Federal Register on March 18, 1994 (59 FR 13044), codified at Code of Federal Regulations at 40 CFR part 82, subpart G. You can find a complete chronology of SNAP decisions and the appropriate Federal Register citations at http://www.epa.gov/ozone/snap/chron.html. III. Is EPA Listing n-Propyl Bromide as an Acceptable Substitute for Ozone-Depleting Substances? A. What Is EPA Proposing Today? EPA is proposing today to list n-propyl bromide (nPB) acceptable, subject to use conditions, for use as a substitute for CFC-113 and methyl chloroform 1 in metals, precision and electronics cleaning, and acceptable, subject to use conditions, for use as a substitute for CFC-113, methyl chloroform and HCFC-141b in adhesives and aerosol solvent end uses. The use conditions for each end use provide that nPB not contain more than 0.05% isopropyl bromide (iPB) 2 by weight before adding stabilizers or other chemicals. By this, we mean the chemical n-propyl bromide that is produced by the manufacturer or reclaimed by a recycler before other substances are added, such as stabilizers, other solvents, or adhesive solids. End users would need to keep documentation for two years from the date on the documentation to show that the nPB-based product that they are using contains no more than 0.05% iPB in the nPB. EPA's decision is based upon comparing environmental and health risks associated with the use of nPB in specific applications in the United States, compared to other available alternatives. Based on our review, the impact of using nPB in the U.S. does not warrant listing the chemical as an unacceptable substitute under the SNAP program. 1 Methyl chloroform is also referred to as 1,1,1-trichloroethane, TCA, or 1,1,1. 2 iPB is also referred to as 2-bromopropane, 2-propyl bromide, or 2-BP. Its CAS registration number is 75-26-3. We recommend, but do not require, that users in all industrial sectors adhere to EPA's recommended guideline for worker exposure of 25 parts per million (ppm) over an eight-hour time-weighted average. While we believe it is possible to achieve the recommended exposure limit of 25 ppm in the kinds of applications listed above, we are concerned about potentially high emissions and exposure levels of nPB in adhesive applications in particular. Consequently, EPA intends to work with the National Institute for Occupational Safety and Health (NIOSH) to develop information for employers and workers at facilities that use, or could use, nPB. NIOSH and state occupational safety and health agencies will provide technical assistance to help ensure a safe workplace environment if owners or workers request it. EPA strongly recommends that users follow responsible use practices suggested by the manufacturer when using nPB. You can also reduce risk in the workplace by monitoring workers' levels of exposure to nPB. These practices will reduce the risk of toxic effects to workers, as well as reducing the impact of emissions on the environment. B. What Is n-Propyl Bromide? n-propyl bromide (nPB), also called 1-bromopropane, is a non-flammable organic solvent with a strong odor. Its chemical formula is C 3 H 7 Br. Its identification number in Chemical Abstracts Service's registry (CAS Reg. No.) is 106-94-5. nPB is used to remove wax, oil, and grease from electronics, metal, and other materials. It also is used as a carrier solvent in adhesives. Some brand names of products using nPB are: Abzol®, EnSolv®, and Solvon® cleaners, and Whisper Spray and Fire Retardant Soft Seam 6460 adhesives. C. What Industrial Sectors Are Included in Our Proposed Decision? EPA has received petitions under CAA Section 612(d) to add nPB to the list of acceptable alternatives for CFC-113, methyl chloroform, and HCFC-141b in the solvent cleaning sector for general metals, precision, and electronics cleaning, as well as in aerosol solvent and adhesive applications. 3 Today's proposal does not list nPB as a substitute for HCFC-141b for the solvent cleaning sector, but does list nPB as an acceptable substitute for HCFC-141b, subject to use conditions, for aerosol solvents. This is because EPA previously listed HCFC-141b as unacceptable for use in non-aerosol solvent cleaning applications because of the availability of safer alternatives (59 FR 13090; March 18, 1994), and listed HCFC-141b as acceptable for use in aerosol solvents. No one may legally use HCFC-141b for non-aerosol solvent cleaning and, therefore, no one would substitute for its use. 3 EPA also received petitions for using nPB in the foam blowing and fire suppression sectors. Because the information in these petitions about the use of nPB is incomplete, EPA was unable to consider them. Therefore, today's action does not address nPB's use in the foam blowing and fire suppression sectors. The proposal for aerosol solvents only applies to a limited number of aerosol solvent applications because of the Nonessential Products Ban promulgated under Section 610 of the Act which prohibits the sale, distribution, or offer for sale or distribution in interstate commence of many products containing CFCs and HCFCs. All aerosol products, pressurized dispensers and foam products containing or manufactured with CFCs and HCFCs—except those specifically exempted by the regulations at 40 CFR part 82, subpart C, and those that are listed as essential medical devices by the Food and Drug Administration at 21 CFR 2.125(e)—are banned from sale and distribution in the United States. Users of aerosol solvents can purchase them only for those applications that are exempted from the Non-Essential Products Ban. The SNAP program applies to the use of substitutes for ODSs, and thus, applies only to those applications where ODSs may be used. Therefore, today's proposed listing only applies to those specific aerosol solvent applications where ODSs are allowed to be sold. This list of permissible uses is subject to change. Of the allowable applications for aerosol solvents, it is most likely that nPB would be used as a solvent in: • Lubricants, coatings, or cleaning fluids for electrical or electronic equipment; • Lubricants, coatings, or cleaning fluids for aircraft maintenance; or • Spinnerrette lubricants and cleaning sprays used in the production of synthetic fibers. In addition, no one has specifically stated that they use, or intend to use, nPB in coatings or inks. Thus, our proposed ruling only addresses nPB use in the adhesives end use, in the adhesives, coatings, and inks sector. We would require a separate SNAP submission and additional information on nPB use and exposure data in coatings and inks to consider its acceptability in those applications. EPA notes that the SNAP program currently does not cover some uses of solvents, such as manual cleaning, carriers for flame retardants, dry cleaning, or paint stripping. Ozone-depleting solvents were never used in significant quantities in these applications, compared to applications that are covered by the SNAP program, such as vapor degreasing or cold batch cleaning. For further discussion, see the original SNAP rule (March 18, 1994; 59 FR 13089-13090 and 59 FR 13117-13120). We summarize our proposed actions by sector and end use in Table 2 below. Table 2.—Summary of Proposed Actions by Sector and End Use For this industrial sector... in this end use... we propose to list nPB as follows... as a substitute for these ozone depleting substances: CFC-113 methyl chloroform HCFC-141b Solvents Cleaning Metals Cleaning Acceptable, subject to use conditions 1 X X Electronics Cleaning Acceptable, subject to use conditions 1 X X Precision Cleaning Acceptable, subject to use conditions 1 X X Aerosols Aerosol Solvents Acceptable, subject to use conditions 1 X X X Adhesives, Coatings, and Inks Adhesives Acceptable, subject to use conditions 1 X X X 1 In order to use nPB, the nPB would have to contain no more than 0.05% iPB by weight before adding stabilizers or other chemicals. At the end of today's action, you will find language that we are proposing to add as Appendix L to subpart G of 40 CFR part 82 to summarize our proposed listing decisions. Information contained in the “Further Information” column of those tables provides additional information on nPB. Although EPA expects nPB users to conform to all information shown in Appendix L, the “further information” is not part of the regulatory decision, and, therefore, is not mandatory. Also, there may be other legal obligations pertaining to the manufacture, use, handling, disposal of nPB that are not included in the comments listed in Appendix L. IV. What Did EPA Consider for Today's Acceptability Decision? To assess the acceptability of any substitute, including nPB, EPA reviews the environmental and health risks potentially posed by the substitute, including ozone depletion potential, global warming potential, flammability, and toxicity. Today's action on nPB follows the publication of an Advanced Notice of Proposed Rulemaking (ANPRM) published in the Federal Register on February 18, 1999, at 64 FR 8043. The ANPRM provided the public an opportunity to review the information available to the Agency at that time, and requested additional information and comment to assist in the development of regulatory options. In particular, the ANPRM asked for information on those key parameters where information was limited—that is, the toxicity, ozone depletion potential, and market potential of nPB. The Agency also issued a notice on December 18, 2000 which provided the public with an update on the information EPA had received regarding nPB's ODP and toxicity, and provided a summary of anticipated next steps in developing regulations under SNAP for nPB (65 FR 78977). Based on all information now available, EPA is proposing to find nPB acceptable subject to use conditions. The Agency is concerned that excessive exposure to nPB can pose risks of adverse health effects and is recommending a workplace exposure guideline that we believe will protect workers who are exposed to this chemical. EPA is basing this recommendation on several factors, including a review of the toxicological literature and a subsequent risk evaluation conducted according to EPA guidelines (adjusted to represent workplace exposure), and consideration of risk management principles. EPA finds that it is possible to reduce workplace exposure to nPB to acceptable levels with commonly available control equipment or ventilation equipment. Thus, the Agency has concluded that it is appropriate to list nPB as acceptable because there is evidence that it can be used in a way that does not present greater risk than other substitutes. Based on these data, the Agency is proposing to list nPB as acceptable, subject to a use condition, for the non-aerosol solvents cleaning sector, aerosol solvents end use, and adhesives end use because we believe it is feasible to meet the recommended AEL of 25 ppm in the solvents cleaning sector, the aerosol solvents end use, and the adhesives end use. However, EPA expects users to defer to any permissible exposure limit ultimately established by OSHA. We note that section 6 of the Occupational Safety and Health Act requires OSHA to make specific legal findings to support a standard. Specifically, under the case law OSHA can set a standard only where there is “substantial evidence” that the particular standard will provide “significant” risk reduction of a “material” adverse health effect to workers. Because OSHA operates under a different statute, employs different methodology, and will presumably have additional data at some point in the future, OSHA's derivation of a permissible exposure limit (PEL) may result in a different number than the AEL we set using EPA's own methodology and the data available today. Today's proposed decision to find nPB acceptable under the SNAP program is based in part on its relatively low ozone depletion potential when emitted within the continental United States. However, the ODP of nPB varies with latitude; therefore, this decision should not guide decisions of other countries. For example, nPB emitted closer to the equator has a significantly higher ozone depleting potential than nPB emitted from the middle and northern latitudes, which include the continental United States (for a further discussion, see section IV.B. below on Ozone Depletion Potential). EPA recommends that any decisions on the use of nPB outside the U.S. should be based on latitude-specific ODPs and volumes of the chemical projected to be used in those regions. A. Toxicity A primary concern regarding nPB use in the United States is its potential adverse health effects to exposed workers. Since EPA recommended a preliminary exposure guideline in 1999, additional studies have been conducted on the toxicity of nPB and its isomer, iPB. EPA has reviewed available toxicity data in order to develop a contamination limit for iPB and an Acceptable Exposure Limit (AEL) 4 for occupational exposure to nPB that are protective of human health. EPA has also reviewed workplace exposure measurements from several facilities where nPB has been used. 4 An AEL is the SNAP program's generic term for an eight-hour time-weighted average occupational exposure limit. 1. What Acceptable Exposure Limit Is EPA Recommending for n-Propyl Bromide, and Why? Today, EPA is recommending an AEL for nPB of 25 ppm as an eight-hour time-weighted average. Based upon currently available data, EPA believes that workers can be exposed to an average nPB concentration of 25 ppm without appreciable risk of adverse health effects. In addition, like many halogenated solvents, nPB has the potential to be absorbed through the skin, so we recommend avoiding skin exposure to nPB by wearing protective clothing and flexible laminated gloves. The discussion below describes the derivation of the recommended AEL of 25 ppm for workplace exposure. a. Summary of toxicity studies. EPA reviewed all the studies listed in docket numbers A-2001-07 and A-91-42 and the studies cited as references in Section XI at the end of this preamble. The epidemiological data on nPB are limited. An anecdotal report by Sclar described neurotoxic effects seen in one patient who used an nPB-based solvent (Sclar, 1999). Another recently published paper describes three women exhibiting signs of peripheral and central nervous system toxicity, such as stumbling, numbness, urinary incontinence, diarrhea, nausea, difficulty in concentrating, dizziness, and headaches which was attributed to nPB exposure (Ichihara, 2002a). Because detailed exposure data are not available in either of these papers, it is difficult to use this information in a risk assessment. Vibration sense deficits, decreased nerve conduction, and reduced scores on neurological functional tests were reported in female workers in China exposed to nPB between <1 ppm and 49 ppm (Ichihara et al. , 2002b). The study authors concluded that their findings suggest that exposure to nPB at levels below or around 50 ppm may affect peripheral and central nervous system function. However, because only an abstract of the study was available to EPA, it was not possible to determine if the exposures and effects were well-characterized or if the sample was large enough to draw reliable conclusions. As discussed below in section IV.A.1.e, “Feasibility of meeting the AEL for nPB in each industrial sector,” NIOSH has performed a number of health hazard evaluations with measured workplace exposures to nPB. However, only one of these studies attempted to assess health effects (NIOSH, 2002). In this study, NIOSH conducted a voluntary medical survey and performed a complete blood count on those workers who chose to participate (43 out of 70 workers participated). The medical survey included questions on whether workers had headaches at least once per week, and whether workers had difficulty having children. No exposure-response relationship could be identified from these data. The survey was not designed to fully characterize effects on the reproductive system, nor did the study employ a control group (a group of workers who were not exposed to nPB), further limiting the utility of this data for risk assessment. The acute toxicity of nPB has been studied in Sprague-Dawley rats for inhalation (Elf Atochem, 1997), oral (Elf Atochem, 1993), and dermal (Elf Atochem, 1995b) routes of exposure. The 4-hour LC50 (lethal concentration for 50% of the test animals) for inhalation of nPB was 35,000 mg/m3 (Elf Atochem, 1997), with death resulting from pulmonary edema. The LD50 (lethal dose for 50% of the test animals) for gavage dosing of nPB was greater than 2,000 mg/kg (Elf Atochem, 1993). Animals receiving 2,000 mg/kg nPB dermally (with occlusion of the exposure area) showed no cutaneous reactions and no evidence of toxicity (Elf Atochem, 1995b). A skin sensitization test in Guinea pigs was also negative (Elf Atochem, 1995c). Key chronic and subchronic toxicological studies on nPB include a 28-day inhalation study (ClinTrials, 1997a), a 90-day inhalation study (ClinTrials, 1997b), a two-generation reproductive toxicity study (WIL, 2001), and various papers and abstracts published in peer-reviewed scientific journals (Ichihara, 1998, 1999, 2000a, 2000b; Kim, 1999; Wang, 1999; Yu, 2001; Ichihara 2002a, 2002b). The results of these studies consistently show that sensitive health endpoints 5 ( i.e. , the biological effects occurring at the lowest levels of nPB exposure) include effects on the liver (centrilobular vacuolation—cellular changes in the central area of the liver) and on the male reproductive system (decreases in absolute and relative seminal vesicle weights, and reduced sperm count, motility and maturation, and effects on sperm shape). 5 An endpoint is an observable or measurable biological event or chemical concentration ( e.g. , metabolite concentration in a target tissue) used as an index of an effect of a chemical exposure. The ClinTrials 90-day inhalation study showed liver effects at exposures of 400 ppm and above, which is consistent with the effects seen by Kim et al. (1999). Effects of nPB on the central and peripheral nervous system have also been reported, including peripheral nerve degeneration and axonal swelling in the spinal cord at 1000 ppm (Yu, 2001), degeneration of the myelin of peripheral nerves at 800 ppm (Ichihara, 1999), and significantly decreased hind limb grip strength (a measure of motor nerve function) at 400 ppm (Ichihara, 2000b). Concerns over potential reproductive toxicity associated with nPB were initially raised because exposure to iPB, a structural analog of nPB, was associated with significant reproductive effects in both male and female workers (Kim, 1996; Park, 1997; Ichihara, 1997). In animal studies, iPB has been shown to induce estrous cycle alterations, decreases in accessory sex gland weights ( e.g , seminal vesicle, prostate), reductions in sperm counts and sperm motility, and changes in sperm morphology (Yu, 1997; Ichihara, 1997; Kamijima, 1997). Results presented by Ichihara and colleagues indicated that nPB exerts some level of reproductive toxicity in rats (Ichihara et al. , 1998, 1999; Wang, 1999). More recently, two studies have reported effects of nPB on the female reproductive system in rats. In the first study, female rats were dosed at 0, 200, 400, and 800 ppm for eight hours a day for 7 weeks. Tests of vaginal smears showed a significant increase in the number of irregular estrous cycles with extended diestrus 6 in the 400 and 800 ppm dose groups, and dose dependent reduction of the number of normal antral follicles in the 400 ppm group (Yamada, 2003). In the second study, female rats were exposed to 1000 ppm nPB for 7 days per week for three weeks. The ratio of the number of estrous cycles of 6 days or longer to the total number of estrous cycles was calculated for the 1000 ppm exposure group and the control group. This ratio was two times higher in the exposed animals than controls, however, this difference was not statistically significant (Sekiguchi, 2002). 6 Diestrus is a period of sexual inactivity during the estrous cycle. In 1999, the Brominated Solvents Consortium (BSOC), a group of several nPB manufacturers, initiated a two-generation study (WIL, 2001) designed to investigate thoroughly the reproductive toxicity of nPB, as well as to provide additional information on other toxic endpoints of concern, including liver effects, and effects on the central nervous system (CNS). In this study, groups of 25 male and female rats were exposed to nPB via whole-body inhalation. The F0, or first generation, animals were exposed to target air concentrations of 0, 100, 250, 500, or 750 parts per million (ppm) of nPB for 6 hours/day, 7 days/week for at least 70 days prior to mating. The F1, or second generation, animals were exposed to 0, 100, 250, or 500 ppm nPB (infertility in the F0 750 ppm group precluded having an F1 750 ppm group). Exposure of male animals in both generations continued throughout mating to the day prior to study termination. Exposure for female animals in both generations continued throughout mating and gestation through gestation day 20. After birth of the pups, the females' exposure continued on lactation day 5 through the day prior to study termination. In this study, fertility was compromised significantly at 500 ppm, and no live offspring were produced at 750 ppm. There was strong evidence of dose-response in both the parent (F0) and offspring (F1) generations for a constellation of reproductive effects in both males and females, including decreases in sperm motility and changes in sperm morphology, reduced numbers of implantation sites and changes in estrous cycles, and reduced litter size. There were slight decreases (only some of which were statistically significant) at 250 ppm, and even 100 ppm for some reproductive endpoints. Statistically significant effects were observed at 250 ppm for reduced prostate weight in F0 males and increased estrous cycle length F1 females. Sperm motility in the 250 ppm group of F1 males was slightly reduced (84.8%) compared to the control group (88.9%). The difference was statistically significant (p<0.05). The study authors noted, however, that the sperm motility percentage for F1 males was slightly higher than the mean value in the WIL Research Laboratories historical control data (83.2%). Therefore, the authors did not attribute the reduction in sperm motility to exposure to nPB at 250 ppm. Male reproductive effects were consistent with those identified in the Japanese studies previously cited (Ichihara et al. , 1998, 1999, 2000a; Wang, 1999). Liver effects similar to those reported in the ClinTrials (1997b) 90-day inhalation study were observed in males and females in both generations. Increases in liver weights occurred in both sexes following exposure to 500 ppm; corresponding increases in the incidence of minimal to mild hepatocellular vacuolation were observed at 250 ppm in males and 500 ppm in females. The adverse effects on the central and peripheral nervous system reported by Yu (2001) and Ichihara (1999, 2000b) occurred at higher doses than those associated with reproductive and liver effects in the two-generation study. Carcinogenicity/Mutagenicity. Limited in vitro screening assays testing for mutagenicity and potential carcinogenicity have been conducted on nPB. Two studies have been performed investigating the potential mutagenicity of nPB in bacterial strains. Barber et al. (1981) exposed five S. typhimurium strains (TA98, TA100, TA1535, TA1537 and TA1538) to five different vapor concentrations of nPB ranging from 1.1 to 20.3 μmol/plate (135-2497 μg/plate). Exposures were performed in a closed incubation system in the presence and absence of liver S9 fraction (from Arochlor-induced rats). Increases in revertants were observed in only strains TA100 and TA1535 in both the absence and presence of S9; increases were not reported in the other strains. Elf Atochem (1994) exposed the same bacterial strains to nPB concentrations of 100 to 100,000 μg/plate in both the absence and presence of liver S9 (from male Sprague-Dawley rats induced with Arochlor 1254). This protocol also used a closed system (closed stainless-steel vessels). The highest concentration was slightly cytotoxic; however, this assay did test up to the limit dose (5,000 μg/plate) recommended for bacterial reversion assays. Appropriate positive and negative controls were used to determine spontaneous background revertant frequency. No increases in revertants were reported in any strain or condition. Given these conflicting studies, the current data regarding mutagenicity of nPB in bacterial strains are equivocal. Unpublished studies of in vivo micronucleus formation (Elf Atochem 1995a) indicate that nPB is not clastogenic, and a published dominant lethal assay with NPB was negative (Saito-Suzuki et al. 1982). In a cell death bioassay using cultured human liver cells (HepG2 hepatoma), the cytotoxicity of nPB was evaluated at concentrations ≤500 ppm (SLR 2001a). Results of the bioassay indicated that nPB was cytotoxic (measured as decreased cell viability) at the highest concentration tested (500 ppm). There were no positive responses reported at any concentration for tests that evaluated enzyme function, DNA damage, or DNA damage and repair when tested at concentrations up to 500 ppm. A closely related compound, ethyl bromide, is weakly carcinogenic in rodents (Haseman and Lockhart 1994), and iPB has been shown to induce reverse mutations in bacteria (Maeng and Yu 1997). Results from these screening assays for short-term genotoxicity do not suggest significant concerns regarding nPB's potential carcinogenicity, although more data are needed. The National Institute of Environmental Health Sciences' National Toxicology Program (NTP) is planning to conduct carcinogenicity studies in both sexes of rats and mice, which will allow for more definitive conclusions. To date, the NTP has not initiated new experimental studies on nPB, and the data will not be available for several years. b. Derivation of an AEL for nPB. Benchmark Dose Modeling Background. EPA considered two methods to derive a recommended acceptable exposure level for workplace exposure: (1) The use of the no-observed-adverse-effect level (NOAEL) to define the starting point of departure (POD) for the computation of a reference value, and (2) the use of benchmark dose-response (BMD) modeling to define the POD. Both methods are essentially a two-step process, the first step defining a POD, and then the second extrapolating from the POD to a lower, environmentally relevant exposure level. EPA's in-depth analysis uses the BMD modeling approach, for reasons explained below; however, under either approach, one arrives at a similar value. The traditional approach to derive safe exposure limits for numerous chemicals regulated in a variety of programs, including the SNAP program, has been to first determine the NOAEL (or LOAEL if a NOAEL cannot be identified), use the NOAEL as the POD, and then apply uncertainty factors based on EPA's guidelines to determine an appropriate reference value. Using the NOAEL to determine a reference value has long been recognized as having limitations in that it: (1) Is limited to one of the doses in the study; (2) does not account for variability in the estimate of the dose-response, which is due to the characteristics of the study design; (3) does not account for the slope of the dose-response curve; and (4) cannot be applied when there is no NOAEL, except through the application of an additional uncertainty factor (Crump, 1984; Kimmel and Gaylor, 1988). A newer analytic approach is to use benchmark dose modeling to define a point of departure for deriving a reference value or slope factor that is more independent of study design. For risk assessment of nPB, EPA followed the BMD guidelines to develop an AEL. The EPA Risk Assessment Forum has written guidelines for the use of the BMD approach in the assessment of non-cancer health risk (USEPA, 1995b), and the EPA Benchmark Dose Workgroup is in the process of drafting technical guidance for the application of the BMD approach in cancer and non-cancer dose-response assessments. Use of BMD methods involve fitting mathematical models to dose-response data and using the results to select a BMD that is associated with a predetermined benchmark response (BMR) at the low end of the observed range in the studies used, such as a 10% increase in the incidence of a particular lesion or a 10% decrease in body weight gain. The BMD derived from mathematical modeling is the central estimate of the dose/exposure associated with the BMR. The point of departure derived from BMD modeling, however, is the Benchmark Dose Lowerbound (BMDL), or the lower 95% bound on the dose/exposure associated with the BMR. Using the lower bound accounts for the uncertainty inherent in a given study ( e.g. , small sample size), and assures (with 95% statistical confidence) that the desired BMR is not exceeded. The advantage of the benchmark dose approach is that it considers response data across all exposure groups. For example, a benchmark dose can be calculated even in studies where a NOAEL could not be identified, i.e. , in studies where responses even in the lowest exposure group tested were considered adverse. Unlike the NOAEL/LOAEL, the benchmark dose does not have to be one of the exposure levels (dose groups) chosen in the experimental design. In a hypothetical experiment where groups of rats are exposed to a chemical at 0 ppm, 100 ppm, 500 ppm and 1,000 ppm, the NOAEL or LOAEL must be either 100 ppm, 500 ppm, or 1,000 ppm simply because those were the only levels tested in the experiment. However, the benchmark dose derived from the data in the same experiment could be 200 ppm, 750 ppm, or even 997 ppm depending on the shape of the dose response curve described by the data. EPA uses the BMD approach whenever possible because it provides a more quantitative alternative to identification of a point of departure than the traditional NOAEL/LOAEL approach (US EPA 1995b). Dosimetric adjustments and application of uncertainty factors. Under either approach—NOAEL/LOAEL or BMD modeling—an adjustment to the point of departure for the calculation of a reference value may be necessary to calculate a “human equivalent concentration” (HEC) if there are differences between the exposure regime used in the toxicity studies and a typical workweek of 8 hours per day and 5 days per week. Once a POD and the corresponding HEC is identified, uncertainty factors (UFs) are applied to account for extrapolation uncertainties that could underestimate the chemical's toxicity potential for exposed humans (in this case, workers using nPB). According to standard risk assessment methods as delineated in Agency guidance (US EPA, 1994), UFs of up to 10 may be applied for each of the following conditions: (1) Data from animal studies are used to estimate effects on humans; (2) Data on healthy people or animals are adjusted to account for variations in sensitivity among members of the human population ( e.g. , interindividual variability); (3) Data from subchronic studies are used to provide estimates for chronic exposure; (4) Studies that only provide a lowest observed adverse effect level (LOAEL) rather than a no observed adverse effect level (NOAEL) or benchmark dose; or (5) An incomplete data base of toxicity information exists for the chemical (US EPA, 1995b). Finally, a modifying factor (MF), which is an additional uncertainty factor that is greater than zero and less than or equal to 10, may be used. The magnitude of the MF depends upon the professional assessment of scientific uncertainties of the study and data base not explicitly treated above, e.g. , the completeness of the overall data base and the number of species tested. The default value for the MF is 1. It is important to note that EPA does not have specific guidelines for occupational studies. As such, EPA is applying its general risk assessment principles and adapting its methodologies, as appropriate to consider risk in an occupational setting. For example, as mentioned above, EPA is adjusting its exposure scenario to derive a human equivalent concentration (HEC) that is representative of workplace exposure, rather than continuous lifetime exposure. Selection of Endpoints for Benchmark Dose Modeling. Based on EPA guidance, endpoints were selected for BMD analysis and for potential use as a point of departure using the following principles: • Toxicological significance of the endpoint • Relevance to humans • Quality of study and dose-response data • Reproducibility of effects across multiple studies. EPA selected reduced sperm motility and increased liver vacuolation for BMD analysis because they met the above criteria, and because these effects were seen consistently throughout the toxicological database at low exposures. EPA guidance states that endpoints selected as appropriate for risk assessment should be modeled if their LOAEL is up to 10-fold above the lowest LOAEL. This ensures that no endpoints with the potential to have the lowest BMDL are excluded from the analysis. The selection of the most appropriate BMDs to use for determining the point of departure must be made by the risk assessor using scientific judgement and principles of risk assessment, as well as the results of the modeling process. Toxicological Evaluation for AEL Derivation. Benchmark dose modeling was conducted following EPA guidelines. EPA modeled six data sets for liver vacuolation and reduced sperm motility based on results from two studies to identify the lowest BMDL as a point of departure (POD). 7 EPA selected these endpoints for BMD analysis because they were consistently found to be the most sensitive effect across the many studies that were conducted on the compound. Further, these particular studies provided robust data on these endpoints so that BMD analysis could be conducted. Based on this analysis, sperm motility in the F1 males from the WIL (2001) study was selected as the POD as it would be protective for all effects of nPB. SLR conducted a BMD analysis using data sets for numerous endpoints from 5 studies, including the WIL (2000) and ClinTrials (1997b) studies used by EPA (SLR International Corp., 2001b). 8 SLR also identified sperm motility in F1 males from the WIL (2001) study as the lowest BMDL. The SLR BMD analysis is discussed further in section IV.A.1.d. The methods used in development of the AEL based on sperm motility are described below. It is important to note that the animals in the 2-generation study were dosed every day for six hours. As such, the dosing scenario used for the testing procedure does not exactly mirror the human exposure scenario in the workplace of 8 hours per day 5 days per week. However, it is still appropriate to consider the data because they address the most sensitive health endpoints, and because the BMDL is adjusted by deriving a HEC to account for workplace exposures. A more complete discussion of EPA's adjustment of the BMDL is contained in ICF, 2002a. 7 Data sets that were modeled from the WIL study include sperm motility and liver vacuolation in the F0 and F1 generations. Data sets modeled from ClinTrials (1997b) were liver vacuolation in both males and females. 8 SLR International Corp. (2001b) conducted BMD modeling on the following studies: ClinTrials (1997a), ClinTrials (1997b), Ichihara, et al. (2000a and b), and WIL (2001). Reproductive endpoints modeled included sperm count, retained sperm in seminiferous tubules, sperm deformities, sperm motility, epididymal sperm count, fertility index, litter viability, and plasma glucose levels. Other toxicological endpoints modeled included forelimb strength, hind limb strength, motor conduction velocity, distal latency time, plasma creatinine phosphokinase levels, brain cell vacuolation, liver vacuolation in males, and analysis in various parameters associated with effects on blood formation. EPA did not use neurotoxic effects as endpoints for deriving an AEL value since we did not consider this to be one of the most sensitive endpoints. No neurotoxic effects were reported in the 2-generation reproductive toxicity assay (WIL, 2001), and no adverse effects were observed in the functional observational battery analysis, either in an abbreviated form in the 28-day study at exposure concentrations of 400 and 1,000 ppm (ClinTrials, 1997a), nor in the 90-day study at concentrations of 400 and 600 ppm (ClinTrials, 1997b). Although the NIOSH voluntary medical survey performed in 1999 attempted to assess symptoms of neurotoxic effects, no exposure-response trend for headache or other neurological effects could be identified from the data. The vacuolation of the white brain matter that was observed in the 28-day study at all exposure concentrations was not observed in the 90-day study, indicating that this effect may be a transient response and not adverse. Further, the vacuolation was not dose-dependent and did not correlate with other gross CNS effects observed at 1,600 ppm in the 28-day study. In the 2-generation study, clinical signs were monitored and CNS effects were not observed at any exposure concentration (0, 100, 250, 500, and 750 ppm) in the F0 or F1 animals, nor were histopathologic lesions observed in the brain, spinal cord or peripheral (sciatic) nerve of rats in the 750-ppm group of the F0 generation in the 2-generation study or in the F1 population. EPA's Benchmark Dose Software (BMDS) was used for model fitting and BMD and BMDL estimation. To derive a BMD and BMDL for reduced sperm motility in the F0 and F1 males from WIL (2001), the data were modeled as continuous effects. Following EPA's Benchmark Dose guidelines, BMDs and BMDLs were defined based on benchmark responses (BMRs) of 10% extra risk—that is, the level at which 10% of the animals would show adverse effects for a particular endpoint. BMDLs were defined as the 95% lower confidence bound on the corresponding BMD estimates. Confidence bounds were calculated by BMDS using a likelihood profile method. The data sets for the reduced sperm motility endpoint were quantitatively summarized by group means and measures of variability (standard errors or standard deviations). The models used to represent the dose-response behavior of these continuous endpoints are those implemented in EPA's Benchmark Dose Software which are the Power model, the Hill model, and the polynomial model. Goodness-of-fit for each model for a given data set was determined based on a likelihood ratio statistic. In particular, maximized log-likelihoods associated with the modeling were sequentially compared. Based on the criteria below, the most appropriate mathematical model and its corresponding BMDL was chosen as the best fit for each of the data sets modeled: 1. Models with an unacceptable fit (including consideration of local fit in the low-dose region) were excluded. Visual fit, particularly in the low-dose region, was assessed for models that had acceptable global goodness-of-fit. 2. If the BMDL values for the remaining models for a given endpoint were within a factor of 3, no model dependence was assumed, and the models were considered indistinguishable in the context of the precision of the methods. The models were then ranked according to the Akaike Information Criterion (AIC), which is reported by the BMDS software to aid in comparing the fit of different models. The model with the lowest AIC (within the family of models) was chosen as the basis for the BMDL. 3. If the BMDL values were not within a factor of 3, some model dependence was assumed, and the lowest BMDL was selected as a reasonable conservative estimate, unless it was an outlier compared to the results from all of the other models. Note that when outliers are removed, the remaining BMDLs may then be within a factor of 3, and so the criteria given in item 2 would be applied. BMDs for reduced sperm motility in F1 and F0 males were 276 ppm and 362 ppm respectively, and BMDLs were 169 ppm and 282 ppm. Consistent with EPA risk assessment guidance, the BMDL of 169 ppm for reduced sperm motility in F1 males (WIL, 2001) was selected as the POD. EPA considered whether a BMDL derived from the F1 generation should be used to determine a workplace exposure limit, particularly in relation to the potential mechanisms by which nPB exerts its effects on the reproductive system. While some mechanistic data are available on this subject, they are inconclusive and limited. The available data do not rule out the possibility that the effects on the F1 generation occurred as a result of effects on parental germ cells (sperm or ova) or effects mediated by changes to the endocrine system. Because of the lack of mechanistic data on developmental and potential transgenerational effects, it is most appropriate and protective, as well as consistent with EPA risk assessment guidelines, to use the endpoint observed at the lowest effect level to derive the AEL. In this case, that endpoint is decreased sperm motility in the F1 generation. The BMDL was multiplied by 6/8 and 7/5 in order to derive the HEC, which accounts for temporal differences between the exposure duration used in the study (6 hours per day, 7 days per week) and an 8-hour per day, 5-day work week. This results in a HEC for spermatic effects of 177 ppm. Uncertainty factors were then applied to the HEC, taking into account the following considerations listed below. (1) An uncertainty factor is needed to account for physiological differences between humans and rats. EPA reference concentration (RfC) guidelines describe the factors that must be considered and state that an uncertainty factor 10 may be used for potential differences between study animals and humans. This factor of 10 is often thought to consist of two uncertainty factors of 3—the first to account for differences in pharmacokinetics 9 and another uncertainty factor to account for differences in pharmacodynamics 10 between the study animal and humans. (The value of 3 is the closest whole number to the square root of 10.) According to EPA RfC guidelines, no adjustment for differences in pharmacokinetics is necessary in this case since the blood/air partition coefficient 11 for nPB in the human (7.1) is less than in the rat (11.7), indicating that the delivered dose of nPB into the bloodstream in rats is slightly higher than in humans. 9 Pharmacokinetics refers to the activity or fate of chemicals in the body, including the processes of absorption, distribution, localization in tissues, biotransformation, and excretion. 10 Pharmacodynamics refers to the biochemical and physiological effects of chemicals in the body and the mechanisms of their actions. 11 A ratio of a chemical's concentration between blood and air when at equilibrium. However, EPA recognizes that the lack of an uncertainty adjustment for pharmacokinetic differences between animals and humans rests on a default approach applied to category 3 gases described in Appendix J of its guidelines for deriving an inhalation RfC. This default approach assumes that the pharmacokinetics of nPB conform to a model that requires several assumptions, in particular: (1) The toxicity is directly related to the inhaled parent compound in the arterial blood, and (2) the critical metabolic pathways scale across species, with respect to body weight, in the same way as the ventilation rate ( e.g. , BW 3/4 ). Given the hypothesized metabolic pathways for nPB (ICF, 2002a; CERHR, 2002a), it is plausible that toxicity in rats may be related to a reactive metabolite in the target tissue rather than the blood level of the parent compound. EPA is not aware of any quantitative data on nPB metabolism in humans, or evidence implicating the biologically active agent or mode of action. EPA requests additional data and comment from the public on nPB pharmacokinetics, metabolism, and mode of action that will help determine whether an interspecies uncertainty factor greater than 1 is appropriate to account for pharmacokinetics. If data become available indicating that nPB does not conform to the constraints assumed by the default pharmacokinetic model in the RfC guidelines, EPA would refine its risk assessment for nPB as necessary, and apply an uncertainty factor for pharmacokinetics in extrapolating from animal to humans. We would also revise our acceptability determinations accordingly. With regard to the UF for pharmacodynamics, no data exist to compare the effect of nPB on human spermatocytes and rat spermatocytes. EPA does not have data suggesting that the default of 3 for pharmacodynamics should not be used. Thus, the full uncertainty factor of 3 for differences in pharmacodynamics was applied. EPA also requests comments and data on this uncertainty factor. (2) Although workers employed in the types of industrial sectors that are part of this SNAP review likely represent a generally healthy population, pre-existing reproductive conditions as well as general variability in fertility would not impact a worker's overt health or employment status, and would be largely unobserved. It is estimated that 6% of adult males are infertile (Purves, 1992), and that 40%-90% of these cases are due to deficient sperm production of unidentifiable origin (Griffin, 1994). Given this information, EPA concludes that a significant portion of the male population has pre-existing reproductive deficits. EPA's risk guidelines for deriving community-based reference concentrations recommend a factor of 10 in accounting for intraspecies variability. EPA believes that in the case of nPB, a lower uncertainty factor is appropriate to account for variability within the worker population. This UF is intended to protect for potential “unobserved” reproductive medical conditions ( e.g. , decreased sperm motility, aberrant sperm formation) that are known to exist among otherwise healthy males of working age. Because we are concerned about exposures in the workplace, not exposures to the full population, and because exposures would not be continuous, such as would be expected when developing an RfC, we employed an UF of three as an upper bound instead of the full uncertainty factor of 10 for intrahuman variability. The following equation describes how EPA derives 18 ppm as a starting point in the development of a recommended AEL using a UF of 3 for variations in the human population, and 3 for pharmacodynamics: 169 ppm * 6/8 * 7/5 * 1/3 * 1/3 ) = 18 ppm This derivation rests on assumptions that some may consider conservative, including the use of the F1 generation as the point of departure for workplace exposure, and the fact that reduced sperm motility may be a particularly sensitive endpoint for male reproductive effects. For a further discussion, see the next section below, “AEL adjustment based on risk management principles.” AEL adjustment based on risk management principles. Risk management uses risk characterization, along with directives of the enabling regulatory legislation and other factors, to decide whether to control exposure to the suspected agent and the level of control. Risk management decisions also consider socioeconomic, technical, and political factors (EPA Reproductive Risk Assessment Guidelines, 1996). Unlike many other chemicals being reviewed by SNAP, nPB is already in use. Therefore, a decision on the AEL that incorporates risk management considerations may be appropriate. Doing so is consistent with one of the original “Guiding Principles” of the SNAP program (59 FR 13046, March 18, 1994): EPA does not intend to restrict a substitute if it poses only marginally greater risk than another substitute. Drawing fine distinctions concerning the acceptability of substitutes would be extremely difficult given the variability in how each substitute can be used within a specific application and the resulting uncertainties surrounding potential health and environmental effects. The Agency also does not want to intercede in the market's choice of available substitutes, unless a substitute has been proposed or is being used that is clearly more harmful to human health and the environment than other alternatives. If EPA adopted 18 ppm as the AEL, we would likely propose that use of nPB be listed as unacceptable in adhesives applications, based on data indicating that exposure to nPB in such uses regularly exceed 18 ppm on average. However, EPA has determined that adhesive operations can meet an AEL of 25 ppm with proper ventilation and controls (see Section IV.A.1.e., “Feasibility of meeting the AEL for nPB in each industrial sector”). The AEL of 18 ppm was derived using assumptions that some may consider conservative. Following the SNAP principle referenced above, some slight adjustment of the AEL may be warranted after applying judgment based on the available data, and after considering alternative derivations. To assess how much of an adjustment may be appropriate that would still be protective of human health, EPA considered potential sources of conservatism in the AEL derivation—specifically, the use of the BMDL in the F1 generation as a point of departure. To assess the magnitude of this conservatism, we derived an AEL based on the BMDL for reduced sperm motility in the F0 generation (282 ppm), the second most sensitive endpoint found in the 2-generation study. Deriving an HEC (296 ppm), and applying the same uncertainty factors as applied to the F1 generation (3 for intraspecies variability and 3 for differences in pharmacodynamics), would result in an occupational exposure limit of approximately 30 ppm. A derivation based on F0 data could be considered as a reasonable and protective upper bound for the occupational exposure limit. EPA requests comment on whether it appropriate to interpret 30 ppm as an upper bound for an occupational exposure limit. EPA has determined that 18 ppm is a reasonable but possibly conservative starting point, and that exposure to 25 ppm would not pose substantially greater risks, while still falling below an upper bound on the occupation exposure limit. An AEL of 25 ppm would reduce overall risk to worker health while adhering to EPA's SNAP guiding principle of not finding a substitute unacceptable unless the proposed substitute is clearly more harmful than other alternatives. EPA specifically requests comment on this approach. Dermal Exposure. EPA believes that workers should use good workplace practices and proper handling procedures to avoid unnecessary dermal exposure to all industrial solvents, including nPB. Similar to other halogenated solvents, nPB may defat the skin and may cause local irritation due to this characteristic. A skin notation is applied to those chemicals where “dermal absorption contributes substantially to the overall systemic toxicity” (skin notation documentation for methyl chloride; ACGIH, 1991). As described previously, the available acute dermal toxicity study in rats (Elf Atochem, 1995) indicates that acute dermal exposure to nPB does not result in systemic toxicity. Because significant dermal absorption of nPB was not demonstrated in this study, EPA is not including a skin notation for nPB along with our recommended AEL in the comments section of the regulatory text. The database regarding dermal toxicity for nPB is not as conclusive as the data for chemicals that have a skin notation, ( e.g. , methyl chloride, dichlorvos). To apply a skin notation to nPB would imply that the dermal toxicity of this compound is similar to that of these other compounds. It is also noteworthy that there is no skin notation for other halogenated solvents such as methylene chloride or perchloroethylene, and there is no evidence that absorption through the skin is greater for nPB than for the other halogenated compounds. Thus, in EPA's judgement the database currently does not support the need for a skin notation for nPB. However, we note that the acute dermal study did not provide information regarding chronic dermal absorption. Further, NIOSH evaluated the potential of nPB to permeate skin and promote chronic, systemic toxicity using a mathematical model and the log octanol::water coefficient for nPB, which is approximately 2. This evaluation found that nPB dermal exposure may be an additional source of exposure to workers if the unprotected skin of both hands is exposed (NIOSH, 2003). Given the above information, EPA specifically requests comment on whether to add a skin notation to our recommended AEL in the final rule if there are data that support this change. c. Overview of the Evaluation of Risks to Human Reproduction (CERHR) Expert Panel Report on nPB. In December 1999, NIOSH submitted an assessment nomination to the National Toxicology Program's (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) for both nPB and iPB. The NTP and the National Institute of Environmental Health Sciences (NIEHS) established CERHR in June 1998. CERHR's purpose is to provide timely, unbiased, scientifically sound evaluations of human and experimental evidence for adverse effects on reproduction, including development, caused by agents to which humans may be exposed. nPB (1-Bromopropane) was nominated by NIOSH and selected for evaluation by the CERHR based primarily on documented evidence of worker exposures and published evidence of reproductive and developmental toxicity in rodents (this evidence is reviewed above in section IV.A.1.a). The evaluation of nPB was a four-month effort by a ten-member Expert Panel of academic, private and government scientists that culminated in a public meeting in December 2001. At that meeting, the Expert Panel reviewed the scientific evidence on nPB and reached conclusions regarding its potential effects on human reproduction and development. The Expert Panel Report on nPB was issued in March 2002 (CERHR, 2002a). An Expert Panel Report on iPB was issued at the same time and is discussed in section IV.A.4. of this preamble (CERHR, 2002b). The Expert Panel Report on nPB is intended to: (1) Interpret the strength of scientific evidence that a given exposure or exposure circumstance may pose a hazard to reproduction and the health and welfare of children; (2) provide objective and scientifically thorough assessments of the scientific evidence that adverse reproductive/developmental health effects are associated with exposure to specific chemicals or classes of chemicals, including descriptions of any uncertainties that would diminish confidence in assessment of risks; and (3) identify knowledge gaps to help establish research and testing priorities. NTP-CERHR sought public comment on the Expert Panel Report through a Federal Register notice on March 8, 2002 (67 FR 10734). The NTP has issued a final report, and has published all the public comments that were received on that report. These documents may be accessed through the CERHR Web site at http://cerhr.niehs.nih.gov/news/bromo/index.html. The conclusions of the March 2002 Expert Panel Report on nPB were as follows: • Available human data are insufficient to draw conclusions on the potential for reproductive or developmental toxicity. • Available toxicological data were sufficient to conclude that nPB exposure can induce developmental and reproductive toxicity in rats. In evaluating the potential effects on human reproduction, the rat data are assumed to be relevant for humans. • The mechanisms that lead to reproductive or developmental toxicity are unknown. • There are no relevant kinetic or metabolism data for nPB to compare human and animal exposure levels. The Expert Panel identified LOAELs from the body of animal data as follows: • A LOAEL for male reproductive effects of 200 ppm based on decreases in absolute and relative seminal vesicle weight reported in Ichihara (2000b). A NOAEL of 100 ppm was identified based on decreases in prostate weight observed at 250 ppm in WIL (2001). • A LOAEL of 250 ppm, and a NOAEL of 100 ppm for female reproduction based on increased estrous cycle length in WIL (2001). • A LOAEL of 250 ppm and a NOAEL of 100 ppm for mineralization of the kidney pelvis in both F0 and F1 generations, based on WIL (2001). EPA agrees with the panel's conclusions that the available human data are insufficient to draw conclusions on the reproductive or developmental toxicity of nPB and that the mechanisms that lead to reproductive or developmental toxicity are unknown. EPA also agrees with the panel that a NOAEL for reproductive effects (male) would be considered to be 100 ppm under a traditional risk assessment analysis. However, based on the criteria described previously for selecting endpoints for BMDL analysis, we believe the CERHR endpoints are not appropriate for developing the AEL for nPB, as explained below. Reduced seminal vesicle weight. EPA did not conduct BMD analysis for reduced seminal vesicle weight observed in the Ichihara (2000b) study because there is no consistency of effect across available studies for this endpoint. Reduced seminal vesicle weight was not found to be a sensitive endpoint in WIL (2001). In fact, a statistically significant reduction in seminal vesicle weight was only seen in the 750 ppm group in the F0 generation, and there were no statistically significant effects on seminal vesicle weight in the F1 generation. Because there were other endpoints that were more sensitive in the WIL study, we regard those endpoints to be of greater toxicological importance. Further, EPA believes that because the Ichihara study was not performed according to GLP guidelines, and there were conflicting reports regarding the exposure regime and the number of animals used, it is not appropriate to use this study in quantitative risk assessment. Reduced absolute prostate weight. Based on the WIL study, the CERHR Expert Panel identified a NOAEL of 100 (with a LOAEL of 250) for reduced absolute prostate weight in the F0 males. The toxicological relevance of absolute prostate weight reduction is questionable since this endpoint may be associated with reduction in overall weight gain. To assess the significance of this particular endpoint, EPA calculated the mean relative prostate weights for exposed dose groups from the WIL (2001) study. Relative prostate weights (organ weight/body weight) in F0 males were 0.0040, 0.0039, 0.0036, 0.0035, and 0.0035 at 0, 100, 250, 500, and 750 ppm respectively, revealing that relative prostate weight at exposures greater than or equal to 250 ppm decreased only 10% relative to controls. Because the dose-response relationship in other endpoints was more pronounced, EPA did not conduct BMD modeling on this endpoint. Increased estrous cycle length. The Expert Panel identified 250 ppm as a LOAEL for females based on increased estrous cycle length in the F1 generation of the WIL (2001) study. EPA agrees that the slight increase in estrous cycle length may be a result of nPB exposure. However, because the estrous cycle length of 4.9 days at 250 ppm is within the range of historical controls, the effect cannot be conclusively attributed to exposure without statistical analysis. The study report also notes lack of cycling in some females, which may have caused difficulty in accurately determining the average estrous cycle length for each affected group. Because these data are lacking, this endpoint should not be used for developing the AEL. Mineralization of the kidney pelvis. The Expert Panel concluded that mineralization of the pelvis of the kidneys at 250 ppm was an adverse effect. EPA notes that mineralization of the kidney was not consistently associated with nPB exposure across different studies, and that in WIL (2001) the severity of mineralization did not increase above a category of minimal except at 750 ppm where it was mild. Therefore, EPA did not consider using this endpoint as useful for developing the AEL. Sperm Motility. The Expert Panel identified 500 ppm as the LOAEL for reduced sperm motility. The Panel agreed with the WIL (2001) study authors that the slight but statistically significant reduction in the percentage of motile sperm in the F1 males at 250 ppm (85% vs. 89% in concurrent control animals) could not be attributed to nPB exposure since the percentage of motile sperm in this dose group slightly exceeded that of historic controls (83%). The data indicate that the small changes observed at 250 ppm are consistent with larger changes in sperm motility observed at 500 and 750 ppm. Thus, results for sperm motility in F0 and F1 males exhibited dose-related trends, and conformed to other principles for the selection of endpoints for BMD analysis (See earlier discussion in section IV.A.1.b.). Thus, regardless of whether a LOAEL of 500 ppm or 250 ppm is assigned to this particular endpoint, the Agency determined that reduction in the percentage of motile sperm in the F1 males is a good candidate for BMD analysis. In addition, it is important to note that the Panel did not have access to either the ICF or SLR International benchmark dose analyses. As discussed in section IV.A.1.b, benchmark dose modeling overcomes the issue of drawing a “bright line” in the form of a LOAEL or NOAEL and instead uses the full set of data across all exposure levels (ICF, Inc., 2002a; SLR International, 2001b). Using the results of benchmark dose modeling, it becomes clear that sperm motility is a sensitive effect, and is an appropriate effect upon which to base an AEL. d. AELs suggested by other reviewers and outside parties. In the draft final nPB risk screen conducted for EPA in preparation for today's proposal, ICF Consulting states that “Given the strength of the data base and the extrapolation of the data to occupational exposures, a range of uncertainty factors to account for variability in the human population of 2 to 3 is considered appropriate.” (ICF, 2002a). EPA recognizes that the choice of UF relates to a wide range of considerations including the strength of the data base. Applying a range of UFs between 2 and 3 to account for intrahuman variability would yield a range of occupational exposure limits between 18 and 30 ppm. ICF suggested that the midpoint of this range, 25 ppm, was an appropriate occupational limit value for the purposes of the risk screen for nPB. EPA requests comment on this recommended approach in deriving an occupational exposure limit, including the application of uncertainty factors. EPA's Office of Atmospheric Programs solicited comments regarding ICF Consulting's analysis and derivation of a recommended AEL from EPA's Office of Research and Development (ORD), external toxicologist William Brock, external toxicologist Darol Dodd, and the State of California, Department of Health Services, Hazard Evaluation System & Information Service (HESIS). The comments are available in docket A-2001-07. ORD's comments focused on the WIL Research Laboratories two-generation study and its use in identifying sensitive endpoints. ORD noted that the study's results indicated dose-related trends, that a number of endpoints were significantly affected at 500 ppm in both generations, and there were slight—though in most cases not statistically significant—decreases at 250 ppm and even 100 ppm for some endpoints. They also stated that “[i]n the absence of evidence of dominant lethality or trans-generational effects typical of endocrine disrupting chemicals, it is reasonable to conclude that the effects of [nPB] are elicited in both sexes via their exposure as adults.” They also noted that “the modest degree of change in the 250 ppm F1 sperm motility endpoint (and lack of significance in the F0 at this dose) compared to the collective more robust changes at 500 ppm, in both the F0 and F1, indicates that 250 ppm could reasonably be considered a NOAEL for nPB, with 500 ppm being a LOAEL.” Finally, ORD noted that “even if the F1 data may not be directly applicable for occupational exposures in males, it certainly is applicable to occupational exposures of pregnant women.” They conclude with suggestions for further research (Klinefelter and Darney, 2002). EPA asked William Brock to review the draft AEL report from a general toxicological point of view. Dr. Brock is currently a senior manager with Environ Corporation. In his review, Dr. Brock noted that several subchronic studies in rats have been conducted with nPB with concentrations ranging from approximately 100 ppm to 1800 ppm. Biological effects have been on liver, male reproductive tissue, and, to some extent, hematological parameters. Although some of the studies have not been conducted according to GLP, this fact does not necessarily limit the usefulness of the studies to recommend an exposure limit. Overall, the sperm effect observed at 400 ppm and the effects on fertility at 500 ppm with hepatic vacuolation at 250 represent the PODs for setting exposure limits for nPB. The NOAEL for these effects would be 200 ppm. Dr. Brock notes that “exposure limits that have historically been established are generally, but no[t] always, an order of magnitude below the NOAEL. Taking this approach would result in an occupational limit of 20 ppm (200/10). Although the ICF report could be improved by being more specific on effects and concentrations, the logic provided in the report and the end result, i.e. , a 25 ppm exposure limit, is certainly justified” (Brock, 2002). EPA asked Darol Dodd to review and comment on the draft AEL report (ICF, 2000a). Dr. Dodd is currently the Laboratory Director for ManTech Environmental Technology, Inc. In his comments, Dr. Dodd stated that the ICF report provided logical and consistent explanations for selection of the BMDL and uncertainty factors. He noted that several of the studies show LOAEL or NOAEL values at 200 ppm to 250 ppm. In his opinion, “a recommended AEL value that is about one order of magnitude lower than LOAELs/NOAELs in a number of laboratory rodent studies does not appear to be overly protective” (Dodd, 2002). HESIS provided comments on the AEL derivation for nPB that focused on the available studies useful for low-dose risk assessment, identifying the LOAELs and NOAELs from these studies, and identifying their disagreements with the ICF evaluation. Overall, HESIS took issue with the approach used by ICF to derive an AEL: “ICF repeatedly ignores or discounts effects seen with low-level exposures. At most points where a decision based on professional judgment must be made, ICF makes the choice that leads to the highest possible AEL.” HESIS states that, contrary to the ICF approach, an appropriate risk assessment methodology would take a NOAEL, LOAEL or appropriate BMDL, and apply uncertainty factors of 10 for each of the following conditions: (1) Interspecies variation, (2) intraspecies variation, (3) reliance on a LOAEL rather than a NOAEL where necessary, and (4) extrapolation from acute or subchronic exposure to chronic exposure. The total uncertainty factor would be between 1,000 and 10,000. HESIS stated that appropriate endpoints and points of departure would be reduced pup weight seen in the Huntingdon (2001) study at 103 ppm, the neurotoxicity seen in Ichihara (2000a) at 200 ppm, reduced seminal vesicle weight and increase in tailless sperm seen at 200 ppm in Ichihara (2001a), reduced sperm motility at 200 ppm in Wang (1999), CNS pathology (vacuolation of white matter) at 400 ppm seen in ClinTrials (1997a), and from the WIL (2001) study, reduced fertility observed at 100 ppm and other adverse reproductive and kidney effects observed at 250 ppm or the lowest BMDL calculated from all studies. Using any of these points of departure, HESIS suggests that a reasonable AEL could range from less than 0.05 ppm to less than 5 ppm, and recommends an AEL of 1 ppm. HESIS stated that, in deriving the AEL for the liver vacuolation, ICF used no uncertainty factor for interspecies pharmacokinetic variation, assuming “without any basis, that gas exchange within the lung constitutes the entire pharmacokinetic variation between the species, simply because the blood-air partition coefficient is lower in humans than in rats.” HESIS also disagreed with the use of no uncertainty factor for intraspecies variation for liver vacuolation. With regard to ICF's derivation of an AEL for sperm motility, HESIS disagreed with ICF's use of no uncertainty factor for interspecies pharmacokinetic variation for the same reason given for liver vacuolation. HESIS also stated that there “is no data base at all on which to determine the likelihood and degree of interhuman variability in sensitivity to the spermatotoxic effect of [nPB] * * * .” Finally, HESIS stated that nPB “is an organic solvent that is probably well absorbed through the skin and should be listed with a skin notation * * * .” A response from ICF Consultants to HESIS's comments is included in the docket (ICF 2002c). EPA concluded that the issues HESIS raises are, in fact, questioning EPA's risk assessment guidelines that were the basis for the AEL report, rather than comments unique to the AEL for nPB. For example, EPA's risk assessment guidelines allow use of a default uncertainty factor of 1 instead of 3 for pharmacokinetics for nPB and other inhaled gases where the toxicity is from the parent compound, rather than metabolites. As discussed above in section IV.A.1.b, we request comment and data that would confirm or refute the appropriateness of the assumptions in Appendix J of EPA's risk assessment guidelines. In addition, EPA disagrees that the uncertainty factor for variability in the worker population should be the same as that for variability in the general population (10). Because the working population does not include children or the elderly, as is the case for the general population, we do not believe that a full UF of 10 for sensitive subpopulations is necessary. Further, workers are only potentially exposed during a 40-hour workweek and not continuously, as would be expected for the general population. Finally, because of the length of the WIL Laboratories study, we do not believe that it is necessary to add an uncertainty factor to extrapolate from subchronic to chronic exposures. Various chemical manufacturers and solvent formulators have derived their own recommended industrial exposure limits. Albemarle Corporation and Dead Sea Bromine Group, both of whom continue to produce nPB, recommend an AEL of 25 ppm in their Material Data Safety Sheets. Great Lakes Chemical and Atofina recommended AELs of 10 ppm and 5 ppm respectively, although neither of these companies currently sells nPB. Petroferm produces nPB formulations and recommends an exposure limit of 25 ppm. Finally, Enviro Tech International, Poly Systems International, TULSTAR Products, and Amity International, all of whom produce nPB formulations, recommend an exposure limit of 100 ppm. In a November 6, 2000, meeting with EPA, Albemarle explained that its derivation of a workplace exposure guideline of 25 ppm is based upon raw data from the two-generation reproductive study (WIL, 2001). In the fall of 2000, Albemarle analyzed preliminary data from the two highest exposure groups in two-generation study, 750 ppm and 500 ppm, and found evidence of reproductive effects. As a proactive measure while completing analysis of the data, Albemarle started with an exposure level of 250 ppm and divided by a safety factor of 10, yielding an exposure guideline of 25 ppm. EPA has not seen the derivation of Great Lakes Chemical Corporation's workplace exposure guideline of 10 ppm or Atofina's guideline of 5 ppm. The AEL recommended by Enviro Tech International is based on two separate analyses. In the first analysis, Rozman and Doull (2001) recommend an AEL of 60-90 ppm based on the results obtained from a health questionnaire administered as a part of a NIOSH Health Hazard Evaluation at a site where nPB is used as an adhesive (NIOSH, 1999). This AEL derivation was subsequently published in Applied Occupational Environmental Hygiene, the ACGIH's journal, in 2002 (Rozman and Doull, 2002). In their analysis, Rozman and Doull identified the most sensitive endpoint for nPB toxicity as peripheral/central neurotoxicity followed by reproductive toxicity and then liver toxicity. This ranking was based on a subchronic inhalation study by Ichihara (2000b) in which decreased hind limb strength in mice was observed following 4 weeks of exposure at 200 ppm. Rozman and Doull concluded that rats are more sensitive to reproductive effects of nPB than humans based on the NIOSH health survey (NIOSH 2002b), which did not identify any statistically significant reproductive effects in humans exposed to nPB. Based on the NIOSH health survey data, conducted at a facility where nPB was used as an adhesive solvent, Rozman and Doull identified 170 ppm as a no observed effect level (NOEL) in workers who reported having a headache more than once per week. They then applied a safety of 2 to protect nearly all workers, and a safety factor of 3 to provide a larger margin of safety from this adverse effect. This approach resulted in a recommended industrial exposure guideline for nPB of 60-90 ppm. EPA does not agree with Rozman and Doull's AEL recommendation. First, their ranking of neurotoxicity as the most sensitive toxicological endpoint fails to take into account that in the Ichihara study, rats were dosed 8 hours per day for 12 weeks, while in the two-generation study, animals were exposed to nPB for 6 hours per day. Therefore, the exposure levels in the Ichihara study must be adjusted by a factor of 0.75 in order to directly compare doses to the 2 generation study. If this adjustment is made, the LOAEL for the Ichihara study becomes 266 ppm, higher than the LOAEL of 250 ppm for reproductive and liver effects identified in the two-generation study. Further, the results of the Ichihara study conflict with the results of the 90-day inhalation study (ClinTrials, 1997b), in which decreases in grip strength were not observed in rats exposed to levels up to 600 ppm nPB for 6 hours/day for 5 days/week. In fact, in the ClinTrials study, there were no consistent treatment-related changes reported in the rats following 4, 8, or 13 weeks of exposure in any parameter evaluated in a full functional observational battery (a suite of tests designed to assess a full spectrum of neurotoxic effects). Because the LOAEL for neurotoxic effects in Ichihara et al. (2000b) is actually higher than the LOAEL identified in the two-generation study, and because the findings on neurotoxicity from the Ichihara study conflict with the results of the 90-day ClinTrials (1997b) study, it is erroneous to conclude that neurotoxicity is the most sensitive endpoint for nPB exposure. Second, the NIOSH medical survey used by Rozman and Doull is not a suitable basis for deriving an AEL. Use of epidemiological data for a quantitative risk assessment requires that the exposures be well-characterized, that the sample size be large enough to allow for the detection of subtle effects in a statistically significant way, and that comparisons to an unexposed control group be made. The data provided in the NIOSH evaluation do not fit these criteria: (1) The sample size in this study was relatively small (46 participants); (2) the health survey was not given to an unexposed control population for comparison; (3) no obvious exposure-response trend for headache was seen, since the low and medium exposure groups had similar prevalence of headache. For each of the neurological symptoms evaluated in the NIOSH health survey, air concentrations of nPB were not statistically different between those employees reporting the symptom compared to those not reporting the symptom (NIOSH 2002). Finally, EPA disagrees with Rozman and Doull's conclusion that reproductive toxicity did not occur in workers exposed to up to 190 ppm of nPB, which is the basis for their assertion that humans are less sensitive to reproductive health effects of nPB compared to rats (Rozman and Doull, 2001). The NIOSH report states that 3 workers (2 male and 1 female) who had been exposed to between 110 and 157 ppm of nPB reported difficulty in having a child. However, as noted by the authors of the NIOSH report, due to the small sample size and the personal nature of the questions, there were significant limitations in the ability of the NIOSH medical survey to detect reproductive or fertility problems. The data from the NIOSH medical survey should not be used to conclude that rats are more sensitive than humans to reproductive effects of nPB, or to draw any general conclusions regarding the potential reproductive toxicity of nPB in humans. In the second analysis submitted by Enviro Tech, SLR International Corporation derived an AEL for nPB of 156 ppm (SLR International, 2001b). We understand that this derivation is currently undergoing peer review for potential publication in a scientific journal. This analysis used benchmark dose-response modeling using data sets for several effects taken from the various animal toxicity tests that have been conducted with nPB. SLR derived a BMDL at a 10% response level of 156 ppm, based on reduced sperm motility in F1 males from the WIL (2001) study. This BMDL is similar to EPA's BMDL for sperm motility of 169 ppm. SLR stated that “Due to the relative completeness of the toxicological database on nPB, including data on human in vitro bioassays, use of a UF is likely not considered necessary for this chemical.” Thus, SLR's recommended AEL is equivalent to their BMDL. EPA maintains that an uncertainty factor is necessary for protection of sensitive individuals since low sperm count is a condition that can occur in otherwise healthy workers. There are no data indicating that human sperm are less sensitive than rat sperm. In fact, sperm production is less efficient in humans, suggesting that human males are likely to be more susceptible than rats to nPB (Amann, 1986). Further, based on EPA's RfC guidelines, an uncertainty factor of 3 is necessary to account for interspecies differences in pharmacodynamics between rats and humans. Had SLR applied what EPA considers appropriate uncertainty factors, their recommended AEL would have been 17 ppm. In a memorandum submitted to Poly Systems International, Joel Charm, a certified industrial hygienist, supported the analyses by both SLR and Rozman and Doull. Mr. Charm suggested that establishing an occupational exposure level of 100 ppm as a ceiling value (i.e., a level not to be exceeded during any part of the working day), coupled with an effective Product Stewardship program, would help companies maintain exposure to their workers as low as reasonably achievable. He suggests that a Product Stewardship program focused on: (1) Training material on how nPB can be handled and used safely; (2) conducting industrial hygiene evaluations as a service to customers, to develop actual exposure level information for a variety of end uses under varying circumstances; and (3) monitoring the health (including reproductive parameters) of workers would, over time, aid in assessing the validity of the occupational exposure limit selected. He also states that through the Product Stewardship program and the regulatory reporting requirements of the Toxic Substances Control Act (TSCA), Section 8, corrective actions could be taken if necessary. While we do not agree with the AELs derived by Rozman and Doull or by SLR, EPA agrees that producers and formulators of nPB should engage in responsible Product Stewardship programs. Albermarle Corporation has been conducting an extensive stewardship program for nPB involving air sampling and workplace practice evaluation for customers to help ensure exposures below 25 ppm. We also note that, in order to verify if exposure levels are below a ceiling value, it would be necessary to monitor workplace exposure continuously. Periodic evaluations of exposure levels would be sufficient for determining long-term exposure to workers. EPA recommends that workplace exposures should be controlled to levels at or below the AEL in order to avoid risk of adverse health effects. e. Feasibility of meeting the AEL for nPB in each industrial sector. Each of the three sectors EPA is considering in today's proposal could potentially expose workers to nPB in different ways. Therefore, we considered separately whether it is feasible to meet the AEL in each of the three sectors. If EPA becomes aware of further information showing that nPB use is likely to pose unacceptable risks to human health in particular applications or end uses, we will find nPB unacceptable in those applications or end uses. Solvents cleaning . When using industrial cleaning equipment, workers are likely to be exposed to solvent vapors continually over the course of a workday. However, users can control nPB emissions from vapor degreasers by changes to the equipment, as well as changes in operating practice. For example, a user can install an additional set of condensation coils to prevent vapor from leaving the vapor degreaser or defluxer. An operator can tilt pieces to be cleaned to allow the solvent to drain off inside the vapor degreaser instead of evaporating outside of the degreaser where workers will breathe the vapors. Exposure data on nPB used in vapor degreasers indicate that it is possible to maintain exposure levels from 2 to 24 ppm over an 8-hour average, as measured using personal samplers (Albemarle, 1997). In 1998, Albemarle Corporation also collected workplace monitoring data from metal cleaning operations. Many, although not all, of the samples collected showed concentrations that, extrapolated to an 8-hour period, would remain under 25 ppm. In addition, another manufacturer and distributor of nPB-based solvents stated that, “For a properly designed, installed, operated, and maintained traditional open-top vapor degreaser, experience has shown that eight-hour time weighted operator exposure levels will be < 20 ppm. For enclosed and automated degreasers, lower exposures can be achieved” (Amity UK Ltd, 2001). EPA has only one set of direct exposure data for equipment that cleans using nPB below its boiling point (“cold cleaning”). These data are from a NIOSH Health Hazard Evaluation for a company that produces instrumentation and components for radio and microwave frequency communications. In this study, NIOSH measured exposures to nPB from a cold batch cleaner that was in a special enclosed room with a local exhaust ventilation system. The highest exposure level was 8.4 ppm (NIOSH, 2000b). However, the type of enclosure and ventilation used at this site is not typical of most facilities using cold cleaning equipment. In general, it is expected that it will be more difficult to control emissions from cold cleaning equipment than from vapor degreasers. The design of vapor degreasers reduces emissions from the equipment by boiling the solvent and then causing it to condense, rather than allowing solvent vapors to be emitted. Because cold cleaning equipment may expose workers to high levels of nPB, we recommend that nPB not be used in cold cleaning equipment unless additional engineering controls are instituted to keep worker exposure to levels below the recommended AEL of 25 ppm. The limited data available on manual cleaning indicate that it may be difficult to attain exposures less than 50 ppm when wiping with nPB by hand (Albemarle, 2001). The SNAP program currently does not regulate manual cleaning with solvents. However, we recommend that nPB not be used for manual cleaning because of the likelihood of high exposures. Aerosol Solvents . Only limited data are available on exposure levels to nPB from aerosol solvent usage. Four measurements on a single user showed exposures to nPB that ranged from 5 to 14 ppm over an 8-hour time-weighted average (Albemarle, 2001). Since the user was cleaning brakes on public works equipment, it is possible that the mechanic was working outdoors, or in an area that was only partially enclosed. EPA expects that these data are not representative of the diverse conditions under which aerosol solvents are used. Confidential data from another facility revealed that exposures vary greatly and in some instances can be higher than 200 ppm. In contrast to vapor degreasers, aerosol solvents tend to be used intermittently for short periods of 1-2 minutes. In some cases, aerosols containing nPB are used in confined spaces without ventilation ducts and fans where workers could be exposed to high levels over a short time. Emissions from aerosols are typically not controlled with equipment that captures the nPB vapor, although aerosol users can improve ventilation and reduce exposure levels through a variety of approaches (e.g., fume hoods). Given this information, EPA requests further workplace exposure data on nPB's use as an aerosol solvent. In addition, we request comment on whether nPB should be acceptable for use as an aerosol solvent, or if its use should be limited in this end use (e.g., use limit restricting nPB only to applications with ventilation equipment). EPA believes that users should adhere to a short-term exposure limit (time weighted average over 15 minutes) of three times the AEL. We recommend this short-term exposure limit, which would equal 75 ppm over 15 minutes, in addition to the 8-hour time weighted average of 25 ppm. We believe that limiting short-term exposure to 75 ppm in a 15 minute period of exposure is feasible with proper ventilation and/or low use volumes. We also recommend only using aerosols containing nPB in open or well-ventilated areas. This procedure is recommended for use of any aerosol solvent, compared to use in enclosed, unventilated areas. Adhesives . In adhesives applications, exposures are expected to vary depending upon the particular kind of application. For example, in the foam-fabrication industry, workers generally are exposed to evaporating solvents on a long-term basis. When adhering tops on counters or tables, workers are more likely to have breaks between exposure, with short-term exposure being of greater concern (HSIA, 2001). EPA is aware that it may be difficult to meet the recommended 25 ppm AEL in adhesive applications that are highly emissive. Exposure data from nPB used in adhesives in the foam-fabrication industry show high nPB concentrations within the workplace. At three different foam-fabrication facilities, NIOSH investigators reported that mean exposures to nPB ranged from 60 to 381 ppm (8-hour time weighted averages) (NIOSH, 1999, 2000a, 2000c, 2001). In one facility, average nPB exposures were reduced from 169 ppm to 19 ppm, following installation of ventilation equipment recommended by NIOSH (NIOSH, 2000c). Although use of spray booths at this facility had a dramatic effect of reducing average exposures to nPB, a significant percentage of workers whose jobs required direct use of spray adhesive containing nPB continued to have exposures in excess of 25 ppm. Among sprayers and assemblers working in the Assembly area, 2 of 10 (20%) full-shift samples exceeded 25 ppm, and among sprayers working in the Covers department, 9 of 11 (81%) of samples exceeded 25 ppm, with a maximum of 58 ppm (time-weighted average, TWA). These findings indicate that it may be necessary for employees to wear appropriate respiratory protection where engineering controls do not reduce exposures to or below the AEL. Where respirators are used to protect workers against nPB, employers should be aware that OSHA's Respiratory Protection standard (29 CFR 1910.134) would apply. Because there is evidence that workplace exposures to nPB can be reduced to levels close to or below the recommended AEL, the Agency has concluded that it is appropriate to find the use of nPB acceptable in adhesive applications. Nevertheless, EPA expects that businesses using nPB in adhesive applications may have difficulty meeting the recommended exposure limit without some form of engineering controls such as confining operations to spray booths with ducts and a fan providing ventilation. Further, although use of spray booths at this facility had a dramatic effect of reducing exposures to nPB, as discussed above, some workers whose jobs required direct use of spray adhesive containing nPB continued to be exposed to nPB in excess of 25 ppm. Given this information, EPA requests comment on whether nPB should be acceptable for use in adhesives. EPA conducted a detailed risk screen for nPB use in adhesives applications in the foam fabrication industry (ICF, 2001a , Attachment C) since this represents the most emissive use, and the use where workers and the general population have the highest exposures. Because this highly emissive use passed our risk screen, we did not conduct a formal risk screen for the solvents cleaning sector and aerosol solvents sectors end use, because emissions and worker exposures in these uses are expected to be lower than the adhesives end use. 2. Are There Other Entities That May Set or Recommend Workplace Standards? Under the National Technology Transfer and Advancement Act of 1995, Section 12(d), Public. Law. 104-113, Federal agencies are required to consider using technical standards that are developed or adopted by voluntary consensus standards bodies, using such technical standards as a means to carry out policy objectives or activities. No such standards for occupational exposure to nPB currently exist. In comparison, the American Conference of Governmental Industrial Hygienists (ACGIH) has established threshold limit values (TLVs) for the primary chlorinated solvents used in the same applications as nPB. The most current TLVs for these solvents—25 ppm for perchloroethylene, and 50 ppm for trichloroethylene and methylene chloride—are identical or moderately higher than our proposed recommended guideline for nPB. It is possible that the American Industrial Hygiene Association (AIHA) or the ACGIH will review the toxicity of nPB in the future and set a voluntary standard. AIHA may develop a Workplace Environmental Exposure Limit (WEEL) for nPB. Further, in 2002, the ACGIH listed 1-Bromopropane and 2-Bromopropane (nPB and iPB, respectively) in its list of “Chemical substances and other issues under study.” If either of these standard-setting bodies recommends an exposure limit on nPB, we would make that information available to the public for comment. In the future, OSHA may develop a mandatory exposure limit for nPB use in the workplace. The result of OSHA's review could result in a permissible exposure limit (PEL) different from EPA's recommended exposure limit of 25 ppm. Unlike nPB, the chlorinated solvents are regulated by OSHA and have been regularly re-evaluated by OSHA, NIOSH, and EPA ( e.g. , as a National Emission Standard for Hazardous Air Pollu [Text truncated at 120,000 characters. The full text is on the page linked above.] --- Source: Frix Law Library, https://www.frixlaw.com/law-library/documents/fr%3A03-13254. Public record. Not legal advice.