# National Primary Drinking Water Regulations: Stage 2 Disinfectants and Disinfection Byproducts Rule > Briefs, arguments, decisions, and more. URL: https://www.frixlaw.com/law-library/documents/fr%3A06-3 ## Record - **Collection:** Federal Register - **Document type:** Rule - **Published:** January 4, 2006 - **Citation:** 71 FR 388 ## Text ENVIRONMENTAL PROTECTION AGENCY 40 CFR Parts 9, 141, and 142 [EPA-HQ-OW-2002-0043; FRL-8012-1] RIN 2040-AD38 National Primary Drinking Water Regulations: Stage 2 Disinfectants and Disinfection Byproducts Rule AGENCY: Environmental Protection Agency (EPA). ACTION: Final rule. SUMMARY: The Environmental Protection Agency (EPA) is promulgating today's final rule, the Stage 2 Disinfectants and Disinfection Byproducts Rule (DBPR), to provide for increased protection against the potential risks for cancer and reproductive and developmental health effects associated with disinfection byproducts (DBPs). The final Stage 2 DBPR contains maximum contaminant level goals for chloroform, monochloroacetic acid and trichloroacetic acid; National Primary Drinking Water Regulations, which consist of maximum contaminant levels (MCLs) and monitoring, reporting, and public notification requirements for total trihalomethanes (TTHM) and haloacetic acids (HAA5); and revisions to the reduced monitoring requirements for bromate. This document also specifies the best available technologies for the final MCLs. EPA is also approving additional analytical methods for the determination of disinfectants and DBPs in drinking water. EPA believes the Stage 2 DBPR will reduce the potential risks of cancer and reproductive and developmental health effects associated with DBPs by reducing peak and average levels of DBPs in drinking water supplies. The Stage 2 DBPR applies to public water systems (PWSs) that are community water systems (CWSs) or nontransient noncommunity water systems (NTNCWs) that add a primary or residual disinfectant other than ultraviolet light or deliver water that has been treated with a primary or residual disinfectant other than ultraviolet light. This rule also makes minor corrections to drinking water regulations, specifically the Public Notification tables. New endnotes were added to these tables in recent rulemakings; however, the corresponding footnote numbering in the tables was not changed. In addition, this rule makes a minor correction to the Stage 1 Disinfectants and Disinfection Byproducts Rule by replacing a sentence that was inadvertently removed. DATES: This final rule is effective on March 6, 2006. For judicial review purposes, this final rule is promulgated as January 4, 2006. The incorporation by reference of certain publications listed in the rule is approved by the Director of the Federal Register as of March 6, 2006. ADDRESSES: EPA has established a docket for this action under Docket ID No. EPA-HQ-OW-2002-0043. All documents in the docket are listed on the http://www.regulations.gov Web site. Although listed in the index, some information is not publicly available, e.g., CBI or other information whose disclosure is restricted by statute. Certain other material, such as copyrighted material, is not placed on the Internet and will be publicly available only in hard copy form. Publicly available docket materials are available either electronically through http://www.regulations.gov or in hard copy at the Water Docket, EPA/DC, EPA West, Room B102, 1301 Constitution Ave., NW., Washington, DC. The Public Reading Room is open from 10 a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The telephone number for the Public Reading Room is (202) 566-1744, and the telephone number for the Water Docket is (202) 566-2426. FOR FURTHER INFORMATION CONTACT: For technical inquiries, contact Tom Grubbs, Standards and Risk Management Division, Office of Ground Water and Drinking Water (MC 4607M), Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460; telephone number: (202) 564-5262; fax number: (202) 564-3767; e-mail address: grubbs.thomas@epa.gov. For general information, contact the Safe Drinking Water Hotline, Telephone (800) 426-4791. The Safe Drinking Water Hotline is open Monday through Friday, excluding legal holidays, from 10 a.m. to 4 p.m. Eastern Time. SUPPLEMENTARY INFORMATION: I. General Information A. Does This Action Apply to Me? Entities potentially regulated by the Stage 2 DBPR are community and nontransient noncommunity water systems that add a primary or residual disinfectant other than ultraviolet light or deliver water that has been treated with a primary or residual disinfectant other than ultraviolet light. Regulated categories and entities are identified in the following chart. Category Examples of regulated entities Industry Community and nontransient noncommunity water systems that use a primary or residual disinfectant other than ultraviolet light or deliver water that has been treated with a primary or residual disinfectant other than ultraviolet light. State, Local, Tribal, or Federal Governments Community and nontransient noncommunity water systems that use a primary or residual disinfectant other than ultraviolet light or deliver water that has been treated with a primary or residual disinfectant other than ultraviolet light. This table is not intended to be exhaustive, but rather provides a guide for readers regarding entities likely to be regulated by this action. This table lists the types of entities that EPA is now aware could potentially be regulated by this action. Other types of entities not listed in the table could also be regulated. To determine whether your facility is regulated by this action, you should carefully examine the definition of “public water system” in § 141.2 and the section entitled “coverage” (§ 141.3) in Title 40 of the Code of Federal Regulations and applicability criteria in § 141.600 and 141.620 of today's proposal. If you have questions regarding the applicability of this action to a particular entity, contact the person listed in the preceding FOR FURTHER INFORMATION CONTACT section. B. How Can I Get Copies of This Document and Other Related Information? See the ADDRESSES section for information on how to receive a copy of this document and related information. Regional contacts: I. Kevin Reilly, Water Supply Section, JFK Federal Bldg., Room 203, Boston, MA 02203, (617) 565-3616. II. Michael Lowy, Water Supply Section, 290 Broadway, 24th Floor, New York, NY 10007-1866, (212) 637-3830. III. Jason Gambatese, Drinking Water Section (3WM41), 1650 Arch Street, Philadelphia, PA 19103-2029, (215) 814-5759. IV. Robert Burns, Drinking Water Section, 61 Forsyth Street SW., Atlanta, GA 30303, (404) 562-9456. V. Miguel Del Toral, Water Supply Section, 77 W. Jackson Blvd., Chicago, IL 60604, (312) 886-5253. VI. Blake L. Atkins, Drinking Water Section, 1445 Ross Avenue, Dallas, TX 75202, (214) 665-2297. VII. Douglas J. Brune, Drinking Water Management Branch, 901 North 5th Street, Kansas City, KS 66101, (800) 233-0425. VIII. Bob Clement, Public Water Supply Section (8P2-W-MS), 999 18th Street, Suite 500, Denver, CO 80202-2466, (303) 312-6653. IX. Bruce Macler, Water Supply Section, 75 Hawthorne Street, San Francisco, CA 94105, (415) 972-3569. X. Wendy Marshall, Drinking Water Unit, 1200 Sixth Avenue (OW-136), Seattle, WA 98101, (206) 553-1890. Abbreviations Used in This Document ASDWA Association of State Drinking Water Administrators ASTM American Society for Testing and Materials AWWA American Water Works Association AwwaRF American Water Works Association Research Foundation BAT Best available technology BCAA Bromochloroacetic acid BDCM Bromodichloromethane CDBG Community Development Block Grant CWS Community water system DBAA Dibromoacetic acid DBCM Dibromochloromethane DBP Disinfection byproduct DBPR Disinfectants and Disinfection Byproducts Rule DCAA Dichloroacetic acid EA Economic analysis EC Enhanced coagulation EDA Ethylenediamine EPA United States Environmental Protection Agency ESWTR Enhanced Surface Water Treatment Rule FACA Federal Advisory Committee Act GAC Granular activated carbon GC/ECD Gas chromatography using electron capture detection GWR Ground Water Rule GWUDI Ground water under the direct influence of surface water HAA5 Haloacetic acids (five) (sum of monochloroacetic acid, dichloroacetic acid, trichloroacetic acid, monobromoacetic acid, and dibromoacetic acid) HAN Haloacetonitriles (trichloroacetonitrile, dichloroacetonitrile, bromochloroacetonitrile, and dibromoacetonitrile) IC Ion chromatograph IC/ICP-MS Ion chromatograph coupled to an inductively coupled plasma mass spectrometer IDSE Initial distribution system evaluation ILSI International Life Sciences Institute IESWTR Interim Enhanced Surface Water Treatment Rule IPCS International Programme on Chemical Safety IRIS Integrated Risk Information System (EPA) LOAEL Lowest observed adverse effect level LRAA Locational running annual average LT1ESTWR Long Term 1 Enhanced Surface Water Treatment Rule LT2ESTWR Long Term 2 Enhanced Surface Water Treatment Rule MBAA Monobromoacetic acid MCAA Monochloroacetic acid MCL Maximum contaminant level MCLG Maximum contaminant level goal M-DBP Microbial and disinfection byproducts mg/L Milligram per liter MRL Minimum reporting level MRDL Maximum residual disinfectant level MRDLG Maximum residual disinfectant level goal NDMA N-nitrosodimethylamine NDWAC National Drinking Water Advisory Council NF Nanofiltration NOAEL No Observed Adverse Effect Level NODA Notice of data availability NPDWR National primary drinking water regulation NRWA National Rural Water Association NTNCWS Nontransient noncommunity water system NTP National Toxicology Program NTTAA National Technology Transfer and Advancement Act OMB Office of Management and Budget PAR Population attributable risk PE Performance evaluation PWS Public water system RAA Running annual average RFA Regulatory Flexibility Act RfD Reference dose RSC Relative source contribution RUS Rural Utility Service SAB Science Advisory Board SBAR Small Business Advisory Review SBREFA Small Business Regulatory Enforcement Fairness Act SDWA Safe Drinking Water Act, or the “Act,” as amended in 1996 SER Small Entity Representative SGA Small for gestational age SUVA Specific ultraviolet absorbance SWAT Surface Water Analytical Tool SWTR Surface Water Treatment Rule TC Total coliforms TCAA Trichloroacetic acid TCR Total Coliform Rule THM Trihalomethane TOC Total organic carbon TTHM Total trihalomethanes (sum of four THMs: chloroform, bromodichloromethane, dibromochloromethane, and bromoform) TWG Technical work group UMRA Unfunded Mandates Reform Act UV 254 Ultraviolet absorption at 254 nm VSL Value of Statistical Life WTP Willingness To Pay Table of Contents I. General Information A. Does This Action Apply to Me? B. How Can I Get Copies of This Document and Other Related Information? II. Summary of the Final Rule A. Why is EPA Promulgating the Stage 2 DBPR? B. What Does the Stage 2 DBPR Require? 1. Initial Distribution System Evaluation 2. Compliance and monitoring requirements 3. Operational Evaluation Levels 4. Consecutive systems C. Correction of § 141.132 III. Background A. Statutory Requirements and Legal Authority B. What is the Regulatory History of the Stage 2 DBPR and How Were Stakeholders Involved? 1. Total Trihalomethanes Rule 2. Stage 1 Disinfectants and Disinfection Byproducts Rule 3. Stakeholder involvement a. Federal Advisory Committee process b. Other outreach processes C. Public Health Concerns to be Addressed 1. What are DBPs? 2. DBP Health Effects a. Cancer health effects i. Epidemiology ii. Toxicology b. Reproductive and developmental health effects i. Epidemiology ii. Toxicology c. Conclusions D. DBP Occurrence and DBP Control 1. Occurrence 2. Treatment E. Conclusions for Regulatory Action IV. Explanation of Today's Action A. MCLGs 1. Chloroform MCLG a. Today's rule b. Background and analysis c. Summary of major comments 2. HAA MCLGs: TCAA and MCAA a. Today's rule b. Background and analysis c. Summary of major comments B. Consecutive Systems 1. Today's Rule 2. Background and analysis 3. Summary of major comments C. LRAA MCLs for TTHM and HAA5 1. Today's rule 2. Background and analysis 3. Summary of major comments D. BAT for TTHM and HAA5 1. Today's rule 2. Background and analysis 3. Summary of major comments E. Compliance Schedules 1. Today's rule 2. Background and analysis 3. Summary of major comments F. Initial Distribution System Evaluation (IDSE) 1. Today's rule a. Applicability b. Data collection i. Standard monitoring ii. System specific study iii. 40/30 certification c. Implementation 2. Background and analysis a. Standard monitoring b. Very small system waivers c. 40/30 certifications d. System specific studies e. Distribution System Schematics 3. Summary of major comments G. Monitoring Requirements and Compliance Determination for TTHM and HAA5 MCLs 1. Today's Rule a. IDSE Monitoring b. Routine Stage 2 Compliance Monitoring i. Reduced monitoring ii. Compliance determination 2. Background and Analysis 3. Summary of Major Comments H. Operational Evaluation Requirements initiated by TTHM and HAA5 Levels 1. Today's rule 2. Background and analysis 3. Summary of major comments I. MCL, BAT, and Monitoring for Bromate 1. Today's rule 2. Background and analysis a. Bromate MCL b. Criterion for reduced bromate monitoring 3. Summary of major comments J. Public Notice Requirements 1. Today's rule 2. Background and analysis 3. Summary of major comments K. Variances and Exemptions 1. Today's Rule 2. Background and Analysis a. Variances b. Affordable Treatment Technologies for Small Systems c. Exemptions 3. Summary of major comments L. Requirements for Systems to Use Qualified Operators M. System Reporting and Recordkeeping Requirements 1. Today's rule 2. Summary of major comments N. Approval of Additional Analytical Methods 1. Today's Rule 2. Background and Analysis O. Laboratory Certification and Approval 1. PE acceptance criteria a. Today's rule b. Background and analysis c. Summary of major comments 2. Minimum reporting limits a. Today's rule b. Background and analysis c. Summary of major comments P. Other regulatory changes V. State Implementation A. Today's rule 1. State Primacy Requirements for Implementation Flexibility 2. State recordkeeping requirements 3. State reporting requirements 4. Interim primacy 5. IDSE implementation B. Background and Analysis C. Summary of Major Comments VI. Economic Analysis A. Regulatory Alternatives Considered B. Analyses that Support Today's Final Rule 1. Predicting water quality and treatment changes 2. Estimating benefits 3. Estimating costs 4. Comparing regulatory alternatives C. Benefits of the Stage 2 DBPR 1. Nonquantified benefits 2. Quantified benefits 3. Timing of benefits accrual D. Costs of the Stage 2 DBPR 1. Total annualized present value costs 2. PWS costs a. IDSE costs b. PWS treatment costs c. Monitoring costs 3. State/Primacy agency costs 4. Non-quantified costs E. Household Costs of the Stage 2 DBPR F. Incremental Costs and Benefits of the Stage 2 DBPR G. Benefits From the Reduction of Co-occurring Contaminants H. Potential Risks From Other Contaminants 1. Emerging DBPs 2. N-nitrosamines 3. Other DBPs I. Effects of the Contaminant on the General Population and Groups within the General Population that are Identified as Likely To Be at Greater Risk of Adverse Health Effects J. Uncertainties in the Risk, Benefit, and Cost Estimates for the Stage 2 DBPR K. Benefit/Cost Determination for the Stage 2 DBPR L. Summary of Major Comments 1. Interpretation of health effects studies 2. Derivation of benefits 3. Use of SWAT 5. Unanticipated risk issues 6. Valuation of cancer cases avoided VII. Statutory and Executive Order Reviews A. Executive Order 12866: Regulatory Planning and Review B. Paperwork Reduction Act C. Regulatory Flexibility Act D. Unfunded Mandates Reform Act E. Executive Order 13132: Federalism F. Executive Order 13175: Consultation and Coordination With Indian Tribal Governments G. Executive Order 13045: Protection of Children from Environmental Health Risks and Safety Risks H. Executive Order 13211: Actions Concerning Regulations That Significantly Affect Energy Supply, Distribution, or Use I. National Technology Transfer and Advancement Act J. Executive Order 12898: Federal Actions to Address Environmental Justice in Minority Populations or Low-Income Populations K. Consultations with the Science Advisory Board, National Drinking Water Advisory Council, and the Secretary of Health and Human Services L. Plain Language M. Analysis of the Likely Effect of Compliance With the Stage 2 DBPR on the Technical, Managerial, and Financial Capacity of Public Water Systems N. Congressional Review Act VIII. References II. Summary of the Final Rule A. Why is EPA Promulgating the Stage 2 DBPR? The Environmental Protection Agency is finalizing the Stage 2 Disinfectants and Disinfection Byproduct Rule (DBPR) to reduce potential cancer risks and address concerns with potential reproductive and developmental risks from DBPs. The Agency is committed to ensuring that all public water systems provide clean and safe drinking water. Disinfectants are an essential element of drinking water treatment because of the barrier they provide against harmful waterborne microbial pathogens. However, disinfectants react with naturally occurring organic and inorganic matter in source water and distribution systems to form disinfection byproducts (DBPs) that may pose health risks. The Stage 2 DBPR is designed to reduce the level of exposure from DBPs without undermining the control of microbial pathogens. The Long Term 2 Enhanced Surface Water Treatment Rule (LT2ESWTR) is being finalized and implemented simultaneously with the Stage 2 DBPR to ensure that drinking water is microbiologically safe at the limits set for DBPs. Congress required EPA to promulgate the Stage 2 DBPR as part of the 1996 Safe Drinking Water Act (SDWA) Amendments (section 1412(b)(2)(C)). The Stage 2 DBPR augments the Stage 1 DBPR that was finalized in 1998 (63 FR 69390, December 16, 1998) (USEPA 1998a). The goal of the Stage 2 DBPR is to target the highest risk systems for changes beyond those required for Stage 1 DBPR. Today's rule reflects consensus recommendations from the Stage 2 Microbial/Disinfection Byproducts (M-DBP) Federal Advisory Committee (the Advisory Committee) as well as public comments. New information on health effects, occurrence, and treatment has become available since the Stage 1 DBPR that supports the need for the Stage 2 DBPR. EPA has completed a more extensive analysis of health effects, particularly reproductive and developmental endpoints, associated with DBPs since the Stage 1 DBPR. Some recent studies on both human epidemiology and animal toxicology have shown possible associations between chlorinated drinking water and reproductive and developmental endpoints such as spontaneous abortion, stillbirth, neural tube and other birth defects, intrauterine growth retardation, and low birth weight. While results of these studies have been mixed, EPA believes they support a potential hazard concern. New epidemiology and toxicology studies evaluating bladder, colon, and rectal cancers have increased the weight of evidence linking these health effects to DBP exposure. The large number of people (more than 260 million Americans) exposed to DBPs and the potential cancer, reproductive, and developmental risks have played a significant role in EPA's decision to move forward with regulatory changes that target lowering DBP exposures beyond the requirements of the Stage 1 DBPR. While the Stage 1 DBPR is predicted to provide a major reduction in DBP exposure, national survey data suggest that some customers may receive drinking water with elevated, or peak, DBP concentrations even when their distribution system is in compliance with the Stage 1 DBPR. Some of these peak concentrations are substantially greater than the Stage 1 DBPR maximum contaminant levels (MCLs) and some customers receive these elevated levels of DBPs on a consistent basis. The new survey results also show that Stage 1 DBPR monitoring sites may not be representative of higher DBP concentrations that occur in distribution systems. In addition, new studies indicate that cost-effective technologies including ultraviolet light (UV) and granular activated carbon (GAC) may be very effective at lowering DBP levels. EPA's analysis of this new occurrence and treatment information indicates that significant public health benefits may be achieved through further, cost-effective reductions of DBPs in distribution systems. The Stage 2 DBPR presents a risk-targeting approach to reduce risks from DBPs. The new requirements provide for more consistent, equitable protection from DBPs across the entire distribution system and the reduction of DBP peaks. New risk-targeting provisions require systems to first identify their risk level; then, only those systems with the greatest risk will need to make operational or treatment changes. The Stage 2 DBPR, in conjunction with the LT2ESWTR, will help public water systems deliver safer water to Americans with the benefits of disinfection to control pathogens and with fewer risks from DBPs. B. What Does the Stage 2 DBPR Require? The risk-targeting components of the Stage 2 DBPR focus the greatest amount of change where the greatest amount of risk may exist. Therefore, the provisions of the Stage 2 DBPR focus first on identifying the higher risks through the Initial Distribution System Evaluation (IDSE). The rule then addresses reducing exposure and lowering DBP peaks in distribution systems by using a new method to determine MCL compliance (locational running annual average (LRAA)), defining operational evaluation levels, and regulating consecutive systems. This section briefly describes the requirements of this final rule. More detailed information on the regulatory requirements for this rule can be found in Section IV. 1. Initial Distribution System Evaluation The first provision, designed to identify higher risk systems, is the Initial Distribution System Evaluation (IDSE). The purpose of the IDSE is to identify Stage 2 DBPR compliance monitoring sites that represent each system's highest levels of DBPs. Because Stage 2 DBPR compliance will be determined at these new monitoring sites, only those systems that identify elevated concentrations of TTHM and HAA5 will need to make treatment or process changes to bring the system into compliance with the Stage 2 DBPR. By identifying compliance monitoring sites with the highest concentrations of TTHM and HAA5 in each system's distribution system, the IDSE will offer increased assurance that MCLs are being met across the distribution system and that customers are receiving more equitable public health protection. Both treatment changes and awareness of TTHM and HAA5 levels resulting from the IDSE will allow systems to better control for distribution system peaks. The IDSE is designed to offer flexibility to public water systems. The IDSE requires TTHM and HAA5 monitoring for one year on a regular schedule that is determined by source water type and system size. Alternatively, systems have the option of performing a site-specific study based on historical data, water distribution system models, or other data; and waivers are available under certain circumstances. The IDSE requirements are discussed in Sections IV.E, IV.F., and IV.G of this preamble and in subpart U of the rule language. 2. Compliance and Monitoring Requirements As in Stage 1, the Stage 2 DBPR focuses on monitoring for and reducing concentrations of two classes of DBPs: total trihalomethanes (TTHM) and haloacetic acids (HAA5). These two groups of DBPs act as indicators for the various byproducts that are present in water disinfected with chlorine or chloramine. This means that concentrations of TTHM and HAA5 are monitored for compliance, but their presence in drinking water is representative of many other chlorination DBPs that may also occur in the water; thus, a reduction in TTHM and HAA5 generally indicates an overall reduction of DBPs. The second provision of the Stage 2 DBPR is designed to address spatial variations in DBP exposure through a new compliance calculation (referred to as locational running annual average) for TTHM and HAA5 MCLs. The MCL values remain the same as in the Stage 1. The Stage 1 DBPR running annual average (RAA) calculation allowed some locations within a distribution system to have higher DBP annual averages than others as long as the system-wide average was below the MCL. The Stage 2 DBPR bases compliance on a locational running annual average (LRAA) calculation, where the annual average at each sampling location in the distribution system will be used to determine compliance with the MCLs of 0.080 mg/L and 0.060 mg/L for TTHM and HAA5, respectively. The LRAA will reduce exposures to high DBP concentrations by ensuring that each monitoring site is in compliance with the MCLs as an annual average, while providing all customers drinking water that more consistently meets the MCLs. A more detailed discussion of Stage 2 DBPR MCL requirements can be found in Sections IV.C, IV.E, and IV.G of this preamble and in § 141.64(b)(2) and (3) and subpart V of the rule language. The number of compliance monitoring sites is based on the population served and the source water type. EPA believes that population-based monitoring provides better risk-targeting and is easier to implement. Section IV.G describes population-based monitoring and how it affects systems complying with this rule. The Stage 2 DBPR includes new MCLGs for chloroform, monochloroacetic acid, and trichloroacetic acid, but these new MCLGs do not affect the MCLs for TTHM or HAA5. 3. Operational Evaluation Levels The IDSE and LRAA calculation will lead to lower DBP concentrations overall and reduce short term exposures to high DBP concentrations in certain areas, but this strengthened approach to regulating DBPs will still allow individual DBP samples above the MCL even when systems are in compliance with the Stage 2 DBPR. Today's rule requires systems that exceed operational evaluation levels (referred to as significant excursions in the proposed rule) to evaluate system operational practices and identify opportunities to reduce DBP concentrations in the distribution system. This provision will curtail peaks by providing systems with a proactive approach to remain in compliance. Operational evaluation requirements are discussed in greater detail in Section IV.H. 4. Consecutive Systems The Stage 2 DBPR also contains provisions for regulating consecutive systems, defined in the Stage 2 DBPR as public water systems that buy or otherwise receive some or all of their finished water from another public water system. Uniform regulation of consecutive systems provided by the Stage 2 DBPR will ensure that consecutive systems deliver drinking water that meets applicable DBP standards, thereby providing better, more equitable public health protection. More information on regulation of consecutive systems can be found in Sections IV.B, IV.E, and IV.G. C. Correction of § 141.132 Section 553 of the Administrative Procedure Act, 5 U.S.C. 553(b)(B), provides that, when an agency for good cause finds that notice and public procedure are impracticable, unnecessary, or contrary to the public interest, the agency may issue a rule without providing prior notice and an opportunity for public comment. In addition to promulgating the Stage 2 regulations, this rule also makes a minor correction to the National Primary Drinking Water Regulations, specifically the Stage 1 Disinfection Byproducts Rule. This rule corrects a technical error made in the January 16, 2001, Federal Register Notice (66 FR 3769) (see page 3770). This rule restores the following sentence that was inadvertently removed from § 141.132 (b)(1)(iii), “Systems on a reduced monitoring schedule may remain on that reduced schedule as long as the average of all samples taken in the year (for systems which must monitor quarterly) or the result of the sample (for systems which must monitor no more frequently than annually) is no more than 0.060 mg/L and 0.045 mg/L for TTHMs and HAA5, respectively.” This text had been part of the original regulation when it was codified in the CFR on December 16, 1998. However, as a result of a subsequent amendment to that regulatory text, the text discussed today was removed. EPA recognized the error only after publication of the new amendment, and is now correcting the error. EPA is merely restoring to the CFR language that EPA had promulgated on December 16, 1998. EPA is not creating any new rights or obligations by this technical correction. Thus, additional notice and public comment is not necessary. EPA finds that this constitutes “good cause” under 5 U.S.C. 553(b)(B). III. Background A combination of factors influenced the development of the Stage 2 DBPR. These include the initial 1992-1994 Microbial and Disinfection Byproduct (M-DBP) stakeholder deliberations and EPA's Stage 1 DBPR proposal (USEPA 1994); the 1996 Safe Drinking Water Act (SDWA) Amendments; the 1996 Information Collection Rule; the 1998 Stage 1 DBPR; new data, research, and analysis on disinfection byproduct (DBP) occurrence, treatment, and health effects since the Stage 1 DBPR; and the Stage 2 DBPR Microbial and Disinfection Byproducts Federal Advisory Committee. The following sections provide summary background information on these subjects. For additional information, see the proposed Stage 2 DBPR and supporting technical material where cited (68 FR 49548, August 18, 2003) (USEPA 2003a). A. Statutory Requirements and Legal Authority The SDWA, as amended in 1996, authorizes EPA to promulgate a national primary drinking water regulation (NPDWR) and publish a maximum contaminant level goal (MCLG) for any contaminant the Administrator determines “may have an adverse effect on the health of persons,” is “known to occur or there is a substantial likelihood that the contaminant will occur in public water systems with a frequency and at levels of public health concern,” and for which “in the sole judgement of the Administrator, regulation of such contaminant presents a meaningful opportunity for health risk reduction for persons served by public water systems” (SDWA section 1412(b)(1)(A)). MCLGs are non-enforceable health goals set at a level at which “no known or anticipated adverse effects on the health of persons occur and which allows an adequate margin of safety.” These health goals are published at the same time as the NPDWR (SDWA sections 1412(b)(4) and 1412(a)(3)). SDWA also requires each NPDWR for which an MCLG is established to specify an MCL that is as close to the MCLG as is feasible (sections 1412(b)(4) and 1401(1)(C)). The Agency may also consider additional health risks from other contaminants and establish an MCL “at a level other than the feasible level, if the technology, treatment techniques, and other means used to determine the feasible level would result in an increase in the health risk from drinking water by—(i) increasing the concentration of other contaminants in drinking water; or (ii) interfering with the efficacy of drinking water treatment techniques or processes that are used to comply with other national primary drinking water regulations” (section 1412(b)(5)(A)). When establishing an MCL or treatment technique under this authority, “the level or levels or treatment techniques shall minimize the overall risk of adverse health effects by balancing the risk from the contaminant and the risk from other contaminants the concentrations of which may be affected by the use of a treatment technique or process that would be employed to attain the maximum contaminant level or levels” (section 1412(b)(5)(B)). In today's rule, the Agency is establishing MCLGs and MCLs for certain DBPs, as described in Section IV. Finally, section 1412(b)(2)(C) of the Act requires EPA to promulgate a Stage 2 DBPR. Consistent with statutory provisions for risk balancing (section 1412(b)(5)(B)), EPA is finalizing the LT2ESWTR concurrently with the Stage 2 DBPR to ensure simultaneous protection from microbial and DBP risks. B. What is the Regulatory History of the Stage 2 DBPR and How Were Stakeholders Involved? This section first summarizes the existing regulations aimed at controlling levels of DBPs in drinking water. The Stage 2 DBPR establishes regulatory requirements beyond these rules that target high risk systems and provide for more equitable protection from DBPs across the entire distribution system. Next, this section summarizes the extensive stakeholder involvement in the development of the Stage 2 DBPR. 1. Total Trihalomethanes Rule The first rule to regulate DBPs was promulgated on November 29, 1979. The Total Trihalomethanes Rule (44 FR 68624, November 29, 1979) (USEPA 1979) set an MCL of 0.10 mg/L for total trihalomethanes (TTHM). Compliance was based on the running annual average (RAA) of quarterly averages of all samples collected throughout the distribution system. This TTHM standard applied only to community water systems using surface water and/or ground water that served at least 10,000 people and added a disinfectant to the drinking water during any part of the treatment process. 2. Stage 1 Disinfectants and Disinfection Byproducts Rule The Stage 1 DBPR, finalized in 1998 (USEPA 1998a), applies to all community and nontransient noncommunity water systems that add a chemical disinfectant to water. The rule established maximum residual disinfectant level goals (MRDLGs) and enforceable maximum residual disinfectant level (MRDL) standards for three chemical disinfectants—chlorine, chloramine, and chlorine dioxide; maximum contaminant level goals (MCLGs) for three trihalomethanes (THMs), two haloacetic acids (HAAs), bromate, and chlorite; and enforceable maximum contaminant level (MCL) standards for TTHM, five haloacetic acids (HAA5), bromate (calculated as running annual averages (RAAs)), and chlorite (based on daily and monthly sampling). The Stage 1 DBPR uses TTHM and HAA5 as indicators of the various DBPs that are present in disinfected water. Under the Stage 1 DBPR, water systems that use surface water or ground water under the direct influence of surface water and use conventional filtration treatment are required to remove specified percentages of organic materials, measured as total organic carbon (TOC), that may react with disinfectants to form DBPs. Removal is achieved through enhanced coagulation or enhanced softening, unless a system meets one or more alternative compliance criteria. The Stage 1 DBPR was one of the first rules to be promulgated under the 1996 SDWA Amendments (USEPA 1998a). EPA finalized the Interim Enhanced Surface Water Treatment Rule (63 FR 69477, December 16, 1998) (USEPA 1998b) at the same time as the Stage 1 DBPR to ensure simultaneous compliance and address risk tradeoff issues. Both rules were products of extensive Federal Advisory Committee deliberations and final consensus recommendations in 1997. 3. Stakeholder Involvement a. Federal Advisory Committee process. EPA reconvened the M-DBP Advisory Committee in March 1999 to develop recommendations on issues pertaining to the Stage 2 DBPR and LT2ESWTR. The Stage 2 M-DBP Advisory Committee consisted of 21 organizational members representing EPA, State and local public health and regulatory agencies, local elected officials, Native American Tribes, large and small drinking water suppliers, chemical and equipment manufacturers, environmental groups, and other stakeholders. Technical support for the Advisory Committee's discussions was provided by a technical working group established by the Advisory Committee. The Advisory Committee held ten meetings from September 1999 to July 2000, which were open to the public, with an opportunity for public comment at each meeting. The Advisory Committee carefully considered extensive new data on the occurrence and health effects of DBPs, as well as costs and potential impacts on public water systems. In addition, they considered risk tradeoffs associated with treatment changes. Based upon this detailed technical evaluation, the committee concluded that a targeted protective public health approach should be taken to address exposure to DBPs beyond the requirements of the Stage 1 DBPR. While there had been substantial research to date, the Advisory Committee also concluded that significant uncertainty remained regarding the risk associated with DBPs in drinking water. After reaching these conclusions, the Advisory Committee developed an Agreement in Principle (65 FR 83015, December 29, 2000) (USEPA 2000a) that laid out their consensus recommendations on how to further control DBPs in public water systems, which are reflected in today's final rule. In the Agreement in Principle, the Advisory Committee recommended maintaining the MCLs for TTHM and HAA5 at 0.080 mg/L and 0.060 mg/L, respectively, but changing the compliance calculation in two phases to facilitate systems moving from the running annual average (RAA) calculation to a locational running annual average (LRAA) calculation. In the first phase, systems would continue to comply with the Stage 1 DBPR MCLs as RAAs and, at the same time, comply with MCLs of 0.120 mg/L for TTHM and 0.100 mg/L for HAA5 calculated as LRAAs. RAA calculations average all samples collected within a distribution system over a one-year period, but LRAA calculations average all samples taken at each individual sampling location in a distribution system during a one-year period. Systems would also carry out an Initial Distribution System Evaluation (IDSE) to select compliance monitoring sites that reflect higher TTHM and HAA5 levels occurring in the distribution system. The second phase of compliance would require MCLs of 0.080 mg/L for TTHM and 0.060 mg/L for HAA5, calculated as LRAAs at individual monitoring sites identified through the IDSE. The first phase has been dropped in the final rule, as discussed in section IV.C. The Agreement in Principle also provided recommendations for simultaneous compliance with the LT2ESWTR so that the reduction of DBPs does not compromise microbial protection. The complete text of the Agreement in Principle (USEPA 2000a) can be found online at www.regulations.gov . b. Other outreach processes. EPA worked with stakeholders to develop the Stage 2 DBPR through various outreach activities other than the M-DBP Federal Advisory Committee process. The Agency consulted with State, local, and Tribal governments; the National Drinking Water Advisory Committee (NDWAC); the Science Advisory Board (SAB); and Small Entity Representatives (SERs) and small system operators (as part of an Agency outreach initiative under the Regulatory Flexibility Act). Section VII includes a complete description of the many stakeholder activities which contributed to the development of the Stage 2 DBPR. Additionally, EPA posted a pre-proposal draft of the Stage 2 DBPR preamble and regulatory language on an EPA Internet site on October 17, 2001. This public review period allowed readers to comment on the Stage 2 DBPR's consistency with the Agreement in Principle of the Stage 2 M-DBP Advisory Committee. EPA received important suggestions on this pre-proposal draft from 14 commenters, which included public water systems, State governments, laboratories, and other stakeholders. C. Public Health Concerns to be Addressed EPA is promulgating the Stage 2 rule to reduce the potential risks of cancer and reproductive and developmental health effects from DBPs. In addition, the provisions of the Stage 2 DBPR provide for more equitable public health protection. Sections C and D describe the general basis for this public health concern through reviewing information in the following areas: the health effects associated with DBPs, DBP occurrence, and the control of DBPs. 1. What Are DBPs? Chlorine has been widely used to kill disease-causing microbes in drinking water. The addition of chlorine in PWSs across the U.S. to kill microbial pathogens in the water supply has been cited as one of the greatest public health advances of the twentieth century (Okun 2003). For example, during the decade 1880-1890, American cities experienced an average mortality rate of 58 per 100,000 from typhoid, which was commonly transmitted through contaminated water. By 1938, this rate had fallen to 0.67 deaths per 100,000, largely due to improved treatment of drinking water (Blake 1956). During the disinfection process, organic and inorganic material in source waters can combine with chlorine and certain other chemical disinfectants to form DBPs. More than 260 million people in the U.S. are exposed to disinfected water and DBPs (USEPA 2005a). Although chlorine is the most commonly applied disinfectant, other disinfectants, including ozone, chlorine dioxide, chloramine, and ultraviolet radiation, are in use. In combination with these, all surface water systems must also use either chlorine or chloramine to maintain a disinfectant residual in their distribution system. The kind of disinfectant used can produce different types and levels of disinfectant byproducts in the drinking water. Many factors affect the amount and kinds of DBPs in drinking water. Areas in the distribution system that have had longer contact time with chemical disinfectants tend to have higher levels of DBPs, such as sites farther from the treatment plant, dead ends in the system, and small diameter pipes. The makeup and source of the water also affect DBP formation. Different types of organic and inorganic material will form different types and levels of DBPs. Other factors, such as water temperature, season, pH, and location within the water purification process where disinfectants are added, can affect DBP formation within and between water systems. THMs and HAAs are widely occurring classes of DBPs formed during disinfection with chlorine and chloramine. The four THMs (TTHM) and five HAAs (HAA5) measured and regulated in the Stage 2 DBPR act as indicators for DBP occurrence. There are other known DBPs in addition to a variety of unidentified DBPs present in disinfected water. THMs and HAAs typically occur at higher levels than other known and unidentified DBPs (McGuire et al. 2002; Weinberg et al. 2002). The presence of TTHM and HAA5 is representative of the occurrence of many other chlorination DBPs; thus, a reduction in the TTHM and HAA5 generally indicates an overall reduction of DBPs. 2. DBP Health Effects Since the mid 1980's, epidemiological studies have supported a potential association between bladder cancer and chlorinated water and possibly also with colon and rectal cancers. In addition, more recent health studies have reported potential associations between chlorinated drinking water and reproductive and developmental health effects. Based on a collective evaluation of both the human epidemiology and animal toxicology data on cancer and reproductive and developmental health effects discussed below and in consideration of the large number of people exposed to chlorinated byproducts in drinking water (more than 260 million), EPA concludes that (1) new cancer data since Stage 1 strengthen the evidence of a potential association of chlorinated water with bladder cancer and suggests an association for colon and rectal cancers, (2) current reproductive and developmental health effects data do not support a conclusion at this time as to whether exposure to chlorinated drinking water or disinfection byproducts causes adverse developmental or reproductive health effects, but do support a potential health concern, and (3) the combined health data indicate a need for public health protection beyond that provided by the Stage 1 DBPR. This section summarizes the key information in the areas of cancer, reproductive, and developmental health studies that EPA used to arrive at these conclusions. Throughout this writeup, EPA uses ‘weight of evidence,' ‘causality,' and ‘hazard' as follows: • A ‘weight of evidence’ evaluation is a collective evaluation of all pertinent information. Judgement about the weight of evidence involves considerations of the quality and adequacy of data and consistency of responses. These factors are not scored mechanically by adding pluses and minuses; they are judged in combination. • Criteria for determining ‘causality’ include consistency, strength, and specificity of association, a temporal relationship, a biological gradient (dose-response relationship), biological plausibility, coherence with multiple lines of evidence, evidence from human populations, and information on agent's structural analogues (USEPA 2005i). Additional considerations for individual study findings include reliable exposure data, statistical power and significance, and freedom from bias and confounding. • The term ‘hazard’ describes not a definitive conclusion, but the possibility that a health effect may be attributed to a certain exposure, in this case chlorinated water. Analyses done for the Stage 2 DBPR follow the 1999 EPA Proposed Guidelines for Carcinogenic Risk Assessment (USEPA 1999a). In March 2005, EPA updated and finalized the Cancer Guidelines and a Supplementary Children's Guidance, which include new considerations on mode of action for cancer risk determination and additional potential risks due to early childhood exposure (USEPA 2005i; USEPA 2005j). Conducting the cancer evaluation using the 2005 Cancer Guidelines would not result in any change from the existing analysis. With the exception of chloroform, no mode of action has been established for other specific regulated DBPs. Although some of the DBPs have given mixed mutagenicity and genotoxicity results, having a positive mutagenicity study does not necessarily mean that a chemical has a mutagenic mode of action. The extra factor of safety for children's health protection does not apply because the new Supplementary Children's Guidance requires application of the children's factor only when a mutagenic mode of action has been identified. a. Cancer health effects. The following section briefly discusses cancer epidemiology and toxicology information EPA analyzed and some conclusions of these studies and reports. Further discussion of these studies and EPA's conclusions can be found in the proposed Stage 2 DBPR (USEPA 2003a) and the Economic Analysis for the Final Stage 2 Disinfectants and Disinfection Byproducts Rule (Economic Analysis (EA)) (USEPA 2005a). Human epidemiology studies and animal toxicology studies have examined associations between chlorinated drinking water or DBPs and cancer. While EPA cannot conclude there is a causal link between exposure to chlorinated surface water and cancer, EPA believes that the available research indicates a potential association between bladder cancer and exposure to chlorinated drinking water or DBPs. EPA also believes the available research suggests a possible association between rectal and colon cancers and exposure to chlorinated drinking water or DBPs. This is based on EPA's evaluation of all available cancer studies. The next two sections focus on studies published since the Stage 1 DBPR. Conclusions are based on the research as a whole. i. Epidemiology. A number of epidemiological studies have been conducted to investigate the relationship between exposure to chlorinated drinking water and various cancers. These studies contribute to the overall evidence on potential human health hazards from exposure to chlorinated drinking water. Epidemiology studies provide useful health effects information because they reflect human exposure to a drinking water DBP mixture through multiple routes of intake such as ingestion, inhalation and dermal absorption. The greatest difficulty with conducting cancer epidemiology studies is the length of time between exposure and effect. Higher quality studies have adequately controlled for confounding and have limited the potential for exposure misclassification, for example, using DBP levels in drinking water as the exposure metric as opposed to type of source water. Study design considerations for interpreting cancer epidemiology data include sufficient follow-up time to detect disease occurrence, adequate sample size, valid ascertainment of cause of the cancer, and reduction of potential selection bias in case-control and cohort studies (by having comparable cases and controls and by limiting loss to follow-up). Epidemiology studies provide extremely useful information on human exposure to chlorinated water, which complement single chemical, high dose animal data. In the Stage 1 DBPR, EPA concluded that the epidemiological evidence suggested a potential increased risk for bladder cancer. Some key studies EPA considered for Stage 1 include Cantor et al. (1998), Doyle et al. (1997), Freedman et al. (1997), King and Marrett (1996), McGeehin et al. (1993), Cantor et al. (1987), and Cantor et al. (1985). Several studies published since the Stage 1 DBPR continue to support an association between increased risk of bladder cancer and exposure to chlorinated surface water (Chevrier et al. 2004; Koivusalo et al. 1998; Yang et al. 1998). One study found no effects on a biomarker of genotoxicity in urinary bladder cells from TTHM exposure (Ranmuthugala et al. 2003). Epidemiological reviews and meta-analyses generally support the possibility of an association between chlorinated water or THMs and bladder cancer (Villanueva et al. 2004; Villanueva et al. 2003; Villanueva et al. 2001; Mills et al. 1998). The World Health Organization (WHO 2000) found data inconclusive or insufficient to determine causality between chlorinated water and any health endpoint, although they concluded that the evidence is better for bladder cancer than for other cancers. In the Stage 1 DBPR, EPA concluded that early studies suggested a small possible increase in rectal and colon cancers from exposure to chlorinated surface waters. The database of studies on colon and rectal cancers continues to support a possible association, but evidence remains mixed. For colon cancer, one newer study supports the evidence of an association (King et al. 2000a) while others showed inconsistent findings (Hildesheim et al. 1998; Yang et al. 1998). Rectal cancer studies are also mixed. Hildesheim et al. (1998) and Yang et al. (1998) support an association with rectal cancer while King et al. (2000a) did not. A review of colon and rectal cancer concluded evidence was inconclusive but that there was a stronger association for rectal cancer and chlorination DBPs than for colon cancer (Mills et al. 1998). The WHO (2000) review reported that studies showed weak to moderate associations with colon and rectal cancers and chlorinated surface water or THMs but that evidence is inadequate to evaluate these associations. Recent studies on kidney, brain, and lung cancers and DBP exposure support a possible association (kidney: Yang et al. 1998, Koivusalo et al. 1998; brain: Cantor et al. 1999; lung: Yang et al. 1998). However, so few studies have examined these endpoints that definitive conclusions cannot be made. Studies on leukemia found little or no association with DBPs (Infante-Rivard et al. 2002; Infante-Rivard et al. 2001). A recent study did not find an association between pancreatic cancer and DBPs (Do et al. 2005). A study researching multiple cancer endpoints found an association between THM exposure and all cancers when grouped together (Vinceti et al. 2004). More details on the cancer epidemiology studies since the Stage 1 DBPR are outlined in Table II.D-1. Table II.D-1.—Summary of Cancer Epidemiology Studies Reviewed for Stage 2 DBPR Study type Exposure(s) studied Outcome(s) measured Findings Author(s) Do et al. 2005 Case-control study in Canada, 1994-1997 Estimated chlorinated DBPs, chloroform, BDCM concentrations Pancreatic cancer No association was found between pancreatic cancer and exposure to chlorinated DBPs, chloroform, or BDCM. Chevrier et al. 2004. Case-control study in France, 1985-1987 Compared THM levels, duration of exposure, and 3 types of water treatment (ozonation, chlorination, ozonation/chlorination) Bladder cancer. A statistically significant decreased risk of bladder cancer was found as duration of exposure to ozonated water increased. This was evident with and without adjustment for other exposure measures. A small association was detected for increased bladder cancer risk and duration of exposure to chlorinated surface water and with the estimated THM content of the water, achieving statistical significance only when adjusted for duration of ozonated water exposures. Effect modification by gender was noted in the adjusted analyses. Vinceti et al. 2004 Retrospective cohort study in Italy, 1987-1999 Standardized mortality ratios from all causes vs. cancer for consumers drinking water with high THMs 15 cancers including colon, rectum, and bladder Mortality ratio from all cancers showed a statistically significant small increase for males consuming drinking water with high THMs. For females, an increased mortality ratio for all cancers was seen but was not statistically significant. Stomach cancer in men was the only individual cancer in which a statistically significant excess in mortality was detected for consumption of drinking water with high THMs. Ranmuthugala et al. 2003 Cohort study in 3 Australian communities, 1997 Estimated dose of TTHM, chloroform, and bromoform from routinely-collected THM measurements and fluid intake diary Frequency of micronuclei in urinary bladder epithelial cells Relative risk estimates for DNA damage to bladder cells for THM dose metrics were near 1.0. The study provides no evidence that THMs are associated with DNA damage to bladder epithelial cells, and dose-response patterns were not detected. Infante-Rivard et al. 2002 Population-based case-control study in Quebec, 1980-1993 Estimated prenatal and postnatal exposure to THMs and polymorphisms in two genes Acute lymphoblastic leukemia Data are suggestive, but imprecise, linking DNA variants with risk of acute lymphoblastic leukemia associated with drinking water DBPs. The number of genotyped subjects for GSTT1 and CYP2E1 genes was too small to be conclusive. Infante-Rivard et al. 2001 Population-based case-control study in Quebec, 1980-1993 Compared water chlorination (never, sometimes, always) and exposure to TTHMs, metals, and nitrates Acute lymphoblastic leukemia No increased risk for lymphoblastic leukemia was observed for prenatal exposure at average levels of TTHMs, metals or nitrates. However, a non-statistically significant, small increased risk was seen for postnatal cumulative exposure to TTHMs and chloroform (both at above the 95th exposure percentile of the distribution for cases and controls), for zinc, cadmium, and arsenic, but not other metals or nitrates. King et al. 2000a Population-based case-control study in southern Ontario, 1992-1994 Compared source of drinking water and chlorination status. Estimated TTHM levels, duration of exposure, and tap water consumption Colon and rectal cancer Colon cancer risk was statistically associated with cumulative long term exposure to THMs, chlorinated surface water, and tap water consumption metrics among males only. Exposure-response relationships were evident for exposure measures combining duration and THM levels. Associations between the exposure measures and rectal cancer were not observed for either gender. Cantor et al. 1999 Population-based case-control study in Iowa, 1984-1987 Compared level and duration of THM exposure (cumulative and average), source of water, chlorination, and water consumption Brain cancer Among males, a statistically significant increased risk of brain cancer was detected for duration of chlorinated versus non-chlorinated source water, especially among high-level consumers of tap water. An increased risk of brain cancer for high water intake level was found in men. No associations were found for women for any of the exposure metrics examined. Cantor et al. 1998 Population-based case-control study in Iowa, 1986-1989 Compared level and duration of THM exposure (cumulative and average), source of water, chlorination, and water consumption Bladder cancer A statistically significant positive association between risk of bladder cancer and exposure to chlorinated groundwater or surface water reported for men and for smokers, but no association found for male/female non-smokers, or for women overall. Limited evidence was found for an association between tapwater consumption and bladder cancer risk. Suggestive evidence existed for exposure-response effects of chlorinated water and lifetime THM measures on bladder cancer risk. Hildesheim et al. 1998 Population-based case-control study in Iowa, 1986-1989 Compared level and duration of THM exposure (cumulative and average), source of water, chlorination, and water consumption Colon and rectal cancer Increased risks of rectal cancer was associated with duration of exposure to chlorinated surface water and any chlorinated water, with evidence of an exposure-response relationship. Risk of rectal cancer is statistically significant increased with >60 years lifetime exposure to THMs in drinking water, and risk increased for individuals with low dietary fiber intake. Risks were similar for men and women and no effects were observed for tapwater measures. No associations were detected for water exposure measures and risk of colon cancer. Koivusalo et al. 1998 Population-based case-control study in Finland, 1991-1992 Estimated residential duration of exposure and level of drinking water mutagenicity Bladder and kidney cancer Drinking water mutagenicity was associated with a small, statistically significant, exposure-related excess risk for kidney and bladder cancers among men; weaker associations were detected for mutagenic water and bladder or kidney cancer among women. The effect of mutagenicity on bladder cancer was modified by smoking status, with an increased risk among non-smokers. Yang et al. 1998 Cross-sectional study in Taiwan, 1982-1991 Examined residence in chlorinated (mainly surface water sources) relative to non-chlorinated (mainly private well) water Cancer of rectum, lung, bladder, kidney, colon, and 11 others Residence in chlorinating municipalities (vs. non-chlorinating) was statistically significantly associated with the following types of cancer in both males and females: rectal, lung, bladder, and kidney cancer. Liver cancer and all cancers were also statistically significantly elevated in chlorinated towns for males only. Mortality rates for cancers of the esophagus, stomach, colon, pancreas, prostate, brain, breast, cervix uteri and uterus, and ovary were comparable for chlorinated and non-chlorinated residence. Doyle et al. 1997 Prospective cohort study in Iowa, 1987-1993 Examined chloroform levels and source of drinking water Colon, rectum, bladder, and 8 other cancers in women Statistically significant increased risk of colon cancer, breast cancer and all cancers combined was observed for women exposed to chloroform in drinking water, with evidence of exposure-response effects. No associations were detected between chloroform and bladder, rectum, kidney, upper digestive organs, lung, ovary, endometrium, or breast cancers, or for melanomas or non-Hodgkin's lymphoma. Surface water exposure (compared to ground water users) was also a significant predictor of colon and breast cancer risk. Freedman et al. 1997 Population-based case-control study in Maryland, 1975-1992 Estimated duration of exposure to chlorinated water. Compared exposure to chlorinated municipal water (yes/no) Bladder cancer There was a weak association between bladder cancer risk and duration of exposure to municipal water for male cigarette smokers, as well as an exposure-response relationship. No association was seen for those with no history of smoking, suggesting that smoking may modify a possible effect of chlorinated surface water on the risk of bladder cancer. King and Marrett 1996 Case-control study in Ontario, Canada, 1992-1994 Compared source of drinking water and chlorination status. Estimated TTHM levels, duration of exposure, and tap water consumption Bladder cancer Statistically significant associations were detected for bladder cancer and chlorinated surface water, duration or concentration of THM levels and tap water consumption metrics. Population attributable risks were estimated at 14 to 16 percent. An exposure-response relationship was observed for estimated duration of high THM exposures and risk of bladder cancer. McGeehin et al. 1993 Population-based case-control study in Colorado, 1990-1991 Compared source of drinking water, water treatment, and tap water versus bottled water. Estimated duration of exposure to TTHMs and levels of TTHMs, nitrates, and residual chlorine Bladder cancer Statistically significant associations were detected for bladder cancer and duration of exposure to chlorinated surface water. The risk was similar for males and females and among nonsmokers and smokers. The attributable risk was estimated at 14.9 percent. High tap water intake was associated with risk of bladder cancer in a exposure-response fashion. No associations were detected between bladder cancer and levels of TTHMs, nitrates, and residual chlorine. Cantor et al. 1987 (and Cantor et al. 1985) Population-based case-control study in 10 areas of the U.S., 1977-1978 Compared source of drinking water. Estimated total beverage and tap water consumption and duration of exposure Bladder cancer Bladder cancer was statistically associated with duration of exposure to chlorinated surface water for women and nonsmokers of both sexes. The largest risks were seen when both exposure duration and level of tap water ingestion were combined. No association was seen for total beverage consumption. Reviews/Meta-analyses Villanueva et al. 2004 Review and meta-analysis of 6 case-control studies Individual-based exposure estimates to THMs and water consumption over a 40-year period Bladder cancer The meta-analysis suggests that risk of bladder cancer in men increases with long-term exposure to TTHMs. An exposure-response pattern was observed among men exposed to TTHMs, with statistically significant risk seen at exposures higher than 50 ug/L. No association between TTHMs and bladder cancer was seen for women. Villanueva et al. 2003 (and Goebell et al. 2004) Review and meta-analysis of 6 case-control studies and 2 cohort studies Compared source of water and estimated duration of exposure to chlorinated drinking water Bladder cancer The meta-analysis findings showed a moderate excess risk of bladder cancer attributable to long-term consumption of chlorinated drinking water for both genders, particularly in men. Statistically significance seen with men and combined both sexes. The risk was higher when exposure exceeded 40 years. Villanueva et al. 2001 Qualitative review of 31 cancer studies Compared exposure to TTHM levels, mutagenic drinking water, water consumption, source water, types of disinfection (chlorination and chloramination), and residence times Cancer of bladder, colon, rectum, and 5 other cancers. Review found that although results for cancer studies varied and were not always statistically significant, evidence for bladder cancer is strongest, and all 10 of the bladder cancer studies showed increased cancer risks with ingestion of chlorinated water. The authors felt associations with chlorinated water and cancer of the colon, rectum, pancreas, esophagus, brain, and other cancers were inconsistent. WHO 2000 Qualitative reviews of various studies in Finland, U.S., and Canada Various exposures to THMs. Various cancers Studies reviewed reported weak to moderate increased relative risks of bladder, colon, rectal, pancreatic, breast, brain or lung cancer associated with long-term exposure to chlorinated drinking water. The authors felt evidence is inconclusive for an association between colon cancer and long-term exposure to THMs; that evidence is insufficient to evaluate a causal relationship between THMs and rectal, bladder, and other cancers. They found no association between THMs and increased risk of cardiovascular disease. Mills et al. 1998 Qualitative review of 22 studies Examined TTHM levels and water consumption. Compared source of water and 2 types of water treatment (chlorination and chloramination) Cancer of colon, rectum, and bladder Review suggests possible increases in risks of bladder cancer with exposure to chlorinated drinking water. The authors felt evidence for increased risk of colon and rectal cancers is inconclusive, though evidence is stronger for rectal cancer. Overall, bladder cancer data provide the strongest basis for quantifying cancer risks from DBPs. EPA has chosen this endpoint to estimate the primary benefits of the Stage 2 DBPR (see Section VI). ii. Toxicology. Cancer toxicology studies provide additional support that chlorinated water is associated with cancer. In general, EPA uses long term toxicology studies that show a dose response to derive MCLGs and cancer potency factors. Short term studies are used for hazard identification and to design long term studies. Much of the available cancer toxicology information was available for the Stage 1 DBPR, but there have also been a number of new cancer toxicology and mode of action studies completed since the Stage 1 DBPR was finalized in December 1998. In support of this rule, EPA has developed health criteria documents which summarize the available toxicology data for brominated THMs (USEPA 2005b), brominated HAAs (USEPA 2005c), MX (USEPA 2000b), MCAA (USEPA 2005d), and TCAA (USEPA 2005e). The 2003 IRIS assessment of DCAA (USEPA 2003b) and an addendum (USEPA 2005k) also provides analysis released after Stage 1. It summarizes information on exposure from drinking water and develops a slope factor for DCAA. IRIS also has toxicological reviews for chloroform (USEPA 2001a), chlorine dioxide and chlorite (USEPA 2000c), and bromate (USEPA 2001b), and is currently reassessing TCAA. Slope factors and risk concentrations for BDCM, bromoform, DBCM and DCAA have been developed and are listed in Table II.D-2. For BDCM, bromoform, and DBCM, table values are derived from the brominated THM criteria document (USEPA 2005b), which uses IRIS numbers that have been updated using the 1999 EPA Proposed Guidelines for Carcinogenic Risk Assessment (USEPA 1999a). For DCAA, the values are derived directly from IRIS. Table II.D-2.—Quantification of Cancer Risk Disinfection byproduct LED 10 a Slope factor (mg/kg/day) −1 10 −6 Risk concentration (mg/L) ED 10 a Slope factor (mg/kg/day) −1 10 −6 Risk concentration (mg/L) Bromodichloromethane 0.034 0.001 0.022 0.002 Bromoform 0.0045 0.008 0.0034 0.01 Dibromochloromethane 0.04 0.0009 0.017 0.002 Dichloroacetic Acid 0.048 0.0007 0.015 b 0.0023 b a LED 10 is the lower 95% confidence bound on the (effective dose) ED 10 value. ED 10 is the estimated dose producing effects in 10% of animals. b The ED 10 risk factors for DCAA have been changed from those given in the comparable table in the proposed Stage 2 DBPR to correct for transcriptional errors. More research on DBPs is underway at EPA and other research institutions. Summaries of on-going studies may be found on EPA's DRINK Web site ( http://www.epa.gov/safewater/drink/intro.html ). Two-year bioassays by the National Toxicology Program (NTP) released in abstract form have recently been completed on BDCM and chlorate. The draft abstract on BDCM reported no evidence of carcinogenicity when BDCM was administered via drinking water (NTP 2005a). Another recent study, a modified two-year bioassay on BDCM in the drinking water, reported little evidence of carcinogenicity (George et al. 2002). In a previous NTP study, tumors were observed, including an increased incidence of kidney, liver, and colon tumors, when BDCM was administered at higher doses by gavage in corn oil (NTP 1987). EPA will examine new information on BDCM as it becomes available. In the chlorate draft abstract, NTP found some evidence that it may be a carcinogen (NTP 2004). Chlorate is a byproduct of hypochlorite and chlorine dioxide systems. A long-term, two-year bioassay NTP study on DBA is also complete but has not yet undergone peer review (NTP 2005b). b. Reproductive and developmental health effects. Both human epidemiology studies and animal toxicology studies have examined associations between chlorinated drinking water or DBPs and reproductive and developmental health effects. Based on an evaluation of the available science, EPA believes the data suggest that exposure to DBPs is a potential reproductive and developmental health hazard. The following section briefly discusses the reproductive and developmental epidemiology and toxicology information available to EPA. Further discussion of these studies and EPA's conclusions can be found in the proposed Stage 2 DBPR (USEPA 2003a) and the Economic Analysis (USEPA 2005a). i. Epidemiology. As discussed previously, epidemiology studies have the strength of relating human exposure to DBP mixtures through multiple intake routes. Although the critical exposure window for reproductive and developmental effects is much smaller than that for cancer (generally weeks versus years), exposure assessment is also a main limitation of reproductive and developmental epidemiology studies. Exposure assessment uncertainties arise from limited data on DBP concentrations and maternal water usage and source over the course of the pregnancy. However, classification errors typically push the true risk estimate towards the null value (Vineis 2004). According to Bove et al. (2002), “Difficulties in assessing exposure may result in exposure misclassification biases that would most likely produce substantial underestimates of risk as well as distorted or attenuated exposure-response trends.” Studies of rare outcomes (e.g., individual birth defects) often have limited statistical power because of the small number of cases being examined. This limits the ability to detect statistically significant associations for small to moderate relative risk estimates. Small sample sizes also result in imprecision around risk estimates reflected by wide confidence intervals. In addition to the limitations of individual studies, evaluating reproductive and developmental epidemiology studies collectively is difficult because of the methodological differences between studies and the wide variety of endpoints examined. These factors may contribute to inconsistencies in the scientific body of literature as noted below. More recent studies tend to be of higher quality because of improved exposure assessments and other methodological advancements. For example, studies that use THM levels to estimate exposure tend to be higher quality than studies that define exposure by source or treatment. These factors were taken into account by EPA when comparing and making conclusions on the reproductive and developmental epidemiology literature. What follows is a summary of available epidemiology literature on reproductive and developmental endpoints such as spontaneous abortion, stillbirth, neural tube and other birth defects, low birth weight, and intrauterine growth retardation. Information is grouped, where appropriate, into three categories on fetal growth, viability, and malformations, and reviews are described separately afterward. Table II.D-3 provides a more detailed description of each study or review. Fetal growth. Many studies looked for an association between fetal growth (mainly small for gestational age, low birth weight, and pre-term delivery) and chlorinated water or DBPs. The results from the collection of studies as a whole are inconsistent. A number of studies support the possibility that exposure to chlorinated water or DBPs are associated with adverse fetal growth effects (Infante-Rivard 2004; Wright et al. 2004; Wright et al. 2003; Källén and Robert 2000; Gallagher et al. 1998; Kanitz et al. 1996; Bove et al. 1995; Kramer et al. 1992). Other studies showed mixed results (Porter et al. 2005; Savitz et al. 2005; Yang 2004) or did not provide evidence of an association (Toledano et al. 2005; Jaakkola et al. 2001; Dodds et al. 1999; Savitz et al. 1995) between DBP exposure and fetal growth. EPA notes that recent, higher quality studies provide some evidence of an increased risk of small for gestational age and low birth weight. Fetal viability. While the database of epidemiology studies for fetal loss endpoints (spontaneous abortion or stillbirth) remains inconsistent as a whole, there is suggestive evidence of an association between fetal loss and chlorinated water or DBP exposure. Various studies support the possibility that exposure to chlorinated water or DBPs is associated with decreased fetal viability (Toledano et al. 2005; Dodds et al. 2004; King et al. 2000b; Dodds et al. 1999; Waller et al. 1998; Aschengrau et al. 1993; Aschengrau et al. 1989). Other studies did not support an association (Bove et al. 1995) or reported inconclusive results (Savitz et al. 2005; Swan et al. 1998; Savitz et al. 1995) between fetal viability and exposure to THMs or tapwater. A recent study by King et al. (2005) found little evidence of an association between stillbirths and haloacetic acids after controlling for trihalomethane exposures, though non-statistically significant increases in stillbirths were seen across various exposure levels. Fetal malformations. A number of epidemiology studies have examined the relationship between fetal malformations (such as neural tube, oral cleft, cardiac, or urinary defects, and chromosomal abnormalities) and chlorinated water or DBPs. It is difficult to assess fetal malformations in aggregate due to inconsistent findings and disparate endpoints being examined in the available studies. Some studies support the possibility that exposure to chlorinated water or DBPs is associated with various fetal malformations (Cedergren et al. 2002; Hwang et al. 2002; Dodds and King 2001; Klotz and Pyrch 1999; Bove et al. 1995; Aschengrau et al. 1993). Other studies found little evidence (Shaw et al. 2003; Källén and Robert 2000; Dodds et al. 1999; Shaw et al. 1991) or inconclusive results (Magnus et al. 1999) between chlorinated water or DBP exposure and fetal malformations. Birth defects most consistently identified as being associated with DBPs include neural tube defects and urinary tract malformations. Other endpoints have also been examined in recent epidemiology studies. One study suggests an association between DBPs and decreased menstrual cycle length (Windham et al. 2003), which, if corroborated, could be linked to the biological basis of other reproductive endpoints observed. No association between THM exposure and semen quality was found (Fenster et al. 2003). More work is needed in both areas to support these results. Reviews. An early review supported an association between measures of fetal viability and tap water (Swan et al. 1992). Three other reviews found data inadequate to support an association between reproductive and developmental health effects and THM exposure (Reif et al. 1996; Craun 1998; WHO 2000). Mills et al. (1998) examined data on and found support for an association between fetal viability and malformations and THMs. Another review presented to the Stage 2 MDBP FACA found some evidence for an association with fetal viability and some fetal malformations and exposure to DBPs but reported that the evidence was inconsistent for these endpoints as well as for fetal growth (Reif et al. 2000). Reif et al. (2000) concluded that the weight of evidence from epidemiology studies suggests that “DBPs are likely to be reproductive toxicants in humans under appropriate exposure conditions,” but from a risk assessment perspective, data are primarily at the hazard identification stage. Nieuwenhuijsen et al. (2000) found some evidence for an association between fetal growth and THM exposure and concluded evidence for associations with other fetal endpoints is weak but gaining weight. A qualitative review by Villanueva et al. (2001) found evidence generally supports a possible association between reproductive effects and drinking chlorinated water. Graves et al. (2001) supports a possible association for fetal growth but not fetal viability or malformations. More recently, Bove et al. (2002) examined and supported an association between small for gestational age, neural tube defects and spontaneous abortion endpoints and DBPs. Following a meta-analysis on five malformation studies, Hwang and Jaakkola (2003) concluded that there was evidence which supported associations between DBPs and risk of birth defects, especially neural tube defects and urinary tract defects. Table II.D-3.—Summary of Reproductive/Developmental Epidemiology Studies Author(s) Study type Exposure(s) studied Outcome(s) measured Findings Porter et al. 2005 Cross-sectional study in Maryland, 1998-2002 Estimated THM and HAA exposure during pregnancy Intrauterine growth retardation No consistent association or dose-response relationship was found between exposure to either TTHM or HAA5 and intrauterine growth retardation. Results suggest an increased risk of intrauterine growth retardation associated with TTHM and HAA5 exposure in the third trimester, although only HAA5 results were statistically significant. Savitz et al. 2005 Population-based prospective cohort study in three communities around the U.S., 2000-2004 Estimated TTHM, HAA9, and TOC exposures during pregnancy. Indices examined included concentration, ingested amount, exposure from showering and bathing, and an integration of all exposures combined Early and late pregnancy loss, preterm birth, small for gestational age, and term birth weight No association with pregnancy loss was seen when looking at high exposure of TTHM compared to low exposure of TTHM. When examining individual THMs, a statistically significant association was found between bromodichloromethane (BDCM) and pregnancy loss. A similar, non-statistically significant association was seen between dibromochloromethane (DBCM) and pregnancy loss. Some increased risk was seen for losses at greater than 12 weeks' gestation for TTHM, BDCM, and TOX (total organic halide), but most results generally did not provide support for an association. Preterm birth showed a small inverse relationship with DBP exposure (i.e. higher exposures showed less preterm births), but this association was weak. TTHM exposure of 80 ug/L was associated with twice the risk for small for gestational age during the third trimester and was statistically significant. Toledano et al. 2005 Large cross-sectional study in England, 1992-1998 Linked mother's residence at time of delivery to modeled estimates of TTHM levels in water zones Stillbirth, low birth weight A significant association between TTHM and risk of stillbirth, low birth weight, and very low birth weight was observed in one of the three regions. When all three regions were combined, small, but non-significant, excess risks were found between all three outcomes and TTHM and chloroform. No associations were observed between reproductive risks and BDCM or total brominated THMs. Dodds et al. 2004 (and King et al. 2005) Population-based case-control study in Nova Scotia and Eastern Ontario, 1999-2001 Estimated THM and HAA exposure at residence during pregnancy. Linked water consumption and showering/bathing to THM exposure Stillbirth A statistically significant association was observed between stillbirths and exposure to total THM, BDCM, and chloroform. Associations were also detected for metrics, which incorporated water consumption, showering and bathing habits. Elevated relative risks were observed for intermediate exposures for total HAA and DCAA measures; TCAA and brominated HAA exposures showed no association. No statistically significant associations or dose-response relationships between any HAAs and stillbirth were detected after controlling for THM exposure. Infante-Rivard 2004 Case-control study of newborns in Montreal, 1998-2000 Estimated THM levels and water consumption during pregnancy. Exposure from showering and presence of two genetic polymorphisms Intrauterine growth retardation No associations were found between exposure to THMs and intrauterine growth retardation. However, a significant effect was observed between THM exposure and intrauterine growth retardation for newborns with the CYP2E1 gene variant. Findings suggest that exposure to THMs at the highest levels can affect fetal growth but only in genetically susceptible newborns. Wright et al. 2004 Large cross-sectional study: Massachusetts, 1995-1998 Estimated maternal third-trimester exposures to TTHMs, chloroform, BDCM, total HAAs, DCA, TCA, MX and mutagenicity in drinking water Birth weight, small for gestational age, preterm delivery, gestational age Statistically significant reductions in mean birth weight were observed for BDCM, chloroform, and mutagenic activity. An exposure-response relationship was found between THM exposure and reductions in mean birth weight and risk of small for gestational age. There was no association between preterm delivery and elevated levels of HAAs, MX, or mutagenicity. A reduced risk of preterm delivery was observed with high THM exposures. Gestational age was associated with exposure to THMs and mutagenicity. Yang et al. 2004 (and Yang et al. 2000) Large cross-sectional studies in Taiwan, 1994-1996 Compared maternal consumption of chlorinated drinking water (yes/no) Low birth weight, preterm delivery Residence in area supplied with chlorinated drinking water showed a statistically significant association with preterm delivery. No association was seen between chlorinated drinking water and low birth weight. Fenster et al. 2003 Small prospective study in California, 1990-1991 Examined TTHM levels within the 90 days preceding semen collection Sperm motility, sperm morphology No association between TTHM level and sperm mobility or morphology. BDCM was inversely associated with linearity of sperm motion. There was some suggestion that water consumption and other ingestion metrics may be associated with different indicators of semen quality. Shaw et al. 2003 2 case-control maternal interview studies: CA, 1987-1991 Estimated THM levels for mothers' residences from before conception through early pregnancy Neural tube defects, oral clefts, selected heart defects No associations or exposure-response relation were observed between malformations and TTHMs in either study. Windham et al. 2003 Prospective study: CA, 1990-1991 Estimated exposure to THMs through showering and ingestion over average of 5.6 menstrual cycles per woman Menstrual cycle, follicular phase length (in days) Findings suggest that THM exposure may affect ovarian function. All brominated THM compounds were associated with significantly shorter menstrual cycles with the strongest finding for chlorodibromomethane. There was little association between TTHM exposure and luteal phase length, menses length, or cycle variability. Wright et al. 2003 Cross-sectional study: Massachusetts, 1990 Estimated TTHM exposure in women during pregnancy (average for pregnancy and during each trimester) Birth weight, small for gestational age, preterm delivery, gestational age Statistically significant associations between 2nd trimester and pregnancy average TTHM exposure and small for gestational age and fetal birth weight were detected. Small, statistically significant increases in gestational duration/age were observed at increased TTHM levels, but there was little evidence of an association between TTHM and preterm delivery or low birth weight. Cedergren et al. 2002 Retrospective case-control study: Sweden, 1982-1997 Examined maternal periconceptional DBP levels and used GIS to assign water supplies Cardiac defects Exposure to chlorine dioxide in drinking water showed statistical significance for cardiac defects. THM concentrations of 10 ug/L and higher were significantly associated with cardiac defects. No excess risk for cardiac defect and nitrate were seen. Hwang et al. 2002 Large cross-sectional study in Norway, 1993-1998 Compared exposure to chlorination (yes/no) and water color levels for mother's residence during pregnancy Birth defects (neural tube defects, cardiac, respiratory system, oral cleft, urinary tract) Risk of any birth defect, cardiac, respiratory system, and urinary tract defects were significantly associated with water chlorination. Exposure to chlorinated drinking water was statistically significantly associated with risk of ventricular septal defects, and an exposure-response pattern was seen. No other specific defects were associated with the exposures that were examined. Dodds and King 2001 Population-based retrospective cohort in Nova Scotia, 1988-1995 Estimated THM, chloroform, and bromodichloromethane (BDCM) exposure Neural tube defects, cardiovascular defects, cleft defects, chromosomal abnormalities Exposure to BDCM was associated with increased risk of neural tube defects, cardiovascular anomalies. Chloroform was not associated with neural tube defects, but was associated with chromosomal abnormalities. No association between THM and cleft defects were detected. Jaakkola et al. 2001 Large cross-sectional study in Norway, 1993-1995 Compared chlorination (yes/no) and water color (high/low) for mother during pregnancy Low birth weight, small for gestational age, preterm delivery No evidence found for association between prenatal exposure to chlorinated drinking water and low birth weight or small for gestational age. A reduced risk of preterm delivery was noted for exposure to chlorinated water with high color content. Källén and Robert 2000 Large cross-sectional cohort study in Sweden, 1985-1994 Linked prenatal exposure to drinking water disinfected with various methods (no chlorine, chlorine dioxide only, sodium hypochlorite only) Gestational duration, birth weight, intrauterine growth, mortality, congenital malformations, and other birth outcomes A statistically significant difference was found for short gestational duration and low birth weight among infants whose mother resided in areas using sodium hypochlorite, but not for chlorine dioxide. Sodium hypochlorite was also associated with other indices of fetal development but not with congenital defects. No other effects were observed for intrauterine growth, childhood cancer, infant mortality, low Apgar score, neonatal jaundice, or neonatal hypothyroidism in relation to either disinfection method. Dodds et al. 1999 (and King et al. 2000b) Population-based retrospective cohort study in Nova Scotia, 1988-1995 Estimated TTHM level for women during pregnancy Low birth weight, preterm birth, small for gestational age, stillbirth, chromosomal abnormalities, neural tube defects, cleft defects, major cardiac defects A statistically significant increased risk for stillbirths and high total THMs and specific THMs during pregnancy was detected, with higher risks observed among asphyxia-related stillbirths. Bromodichloromethane had the strongest association and exhibited an exposure-response pattern. There was limited evidence of an association between THM level and other reproductive outcomes. No congenital anomalies were associated with THM exposure, except for a non-statistically significant association with chromosomal abnormalities. Klotz and Pyrch 1999 (and Klotz and Pyrch 1998) Population-based case-control study in New Jersey, 1993-1994 Estimated exposure of pregnant mothers to TTHMs and HAAs, and compared source of water Neural tube defects A significant association was seen between exposure to THMs and neural tube defects. No associations were observed for neural tube defects and haloacetic acids or haloacetonitriles. Magnus et al. 1999 Large cross-sectional study in Norway, 1993-1995 Compared chlorination (yes/no) and water color (high/low) at mothers' residences at time of birth Birth defects (neural tube defects, major cardiac, respiratory, urinary, oral cleft) Statistically significant associations were seen between urinary tract defects and chlorination and high water color (high content of organic compounds). No associations were detected for other outcomes or all birth defects combined. A non-statistically significant, overall excess risk of birth defects was seen within municipalities with chlorination and high water color compared to municipalities with no chlorination and low color. Gallagher et al. 1998 Retrospective cohort study of newborns in Colorado, 1990-1993 Estimated THM levels in drinking water during third trimester of pregnancy Low birth weight, term low birthweight, and preterm delivery Weak, non-statistically significant association with low birth weight and TTHM exposure during the third trimester. Large statistically significant increase for term low birthweight at highest THM exposure levels. No association between preterm delivery and THM exposure. Swan et al. 1998 Prospective study in California, 1990-1991 Compared consumption of cold tap water to bottled water during early pregnancy Spontaneous abortion Pregnant women who drank cold tap water compared to those who consumed no cold tap water showed a significant finding for spontaneous abortion at one of three sites. Waller et al. 1998 (and Waller et al. 2001) Prospective cohort in California, 1989-1991 Estimated TTHM levels during first trimester of pregnancy via ingestion and showering Spontaneous abortion Statistically significant increased risk between high intake of TTHMs and spontaneous abortion compared to low intake. BDCM statistically associated with increased spontaneous abortion; other THMs not. Reanalysis of exposure yielded less exposure misclassification and relative risks similar in magnitude to earlier study. An exposure-response relationship was seen between spontaneous abortion and ingestion exposure to TTHMs. Kanitz et al. 1996 Cross-sectional study in Italy, 1988-1989 Compared 3 types of water treatment (chlorine dioxide, sodium hypochlorite, and chlorine dioxide/sodium hypochlorite) Low birth weight, body length, cranial circumference, preterm delivery, and other effects Smaller body length and small cranial circumference showed statistical significant association with maternal exposure to chlorinated drinking water. Neonatal jaundice linked statistically to prenatal exposure to drinking water treated with chlorine dioxide. Length of pregnancy, type of delivery, and birthweight showed no association. Bove et al. 1995 (and Bove et al. 1992a & 1992b) Large cohort cross-sectional study in New Jersey, 1985-1988 Examined maternal exposure to TTHM and various other contaminants Low birth weight, fetal deaths, small for gestational age, birth defects (neural tube defects, oral cleft, central nervous system, major cardiac) Weak, statistically significant increased risk found for higher TTHM levels with small for gestational age, neural tube defects, central nervous system defects, oral cleft defects, and major cardiac defects. Some association with higher TTHM exposure and low birth weight. No effect seen for preterm birth, very low birth weight, or fetal deaths. Savitz et al. 1995 Population-based case-control study: North Carolina, 1988-1991 Examined TTHM concentration at residences and water consumption (during first and third trimesters) Spontaneous abortion, preterm delivery, low birth weight There was a statistically significant increased miscarriage risk with high THM concentration, but THM intake (based on concentration times consumption level) was not related to pregnancy outcome. No associations were seen for preterm delivery or low birth weight. Water source was not related to pregnancy outcome either, with the exception of a non-significant, increased risk of spontaneous abortion for bottled water users. There was a non-statistically significant pattern of reduced risk with increased consumption of water for all three outcomes. Aschengrau et al. 1993 Case-control study in Massachusetts, 1977-1980 Source of water and 2 types of water treatment (chlorination, chloramination) Neonatal death, stillbirth, congenital anomalies There was a non-significant, increased association between frequency of stillbirths and maternal exposure to chlorinated versus chloraminated surface water. An increased risk of urinary track and respiratory track defects and chlorinated water was detected. Neonatal death and other major malformations showed no association. No increased risk seen for any adverse pregnancy outcomes for surface water versus ground and mixed water use. Kramer et al. 1992 Population-based case-control study in Iowa, 1989-1990 Examined chloroform, DCBM, DBCM, and bromoform levels and compared type of water source (surface, shallow well, deep well) Low birth weight, prematurity, intrauterine growth retardation Statistically significant increased risk for intrauterine growth retardation effects from chloroform exposure were observed. Non-significant increased risks were observed for low birth weight and chloroform and for intrauterine growth retardation and DCBM. No intrauterine growth retardation or low birth weight effects were seen for the other THMs, and no effects on prematurity were observed for any of the THMs. Shaw et al. 1991 (and Shaw et al. 1990) Small case-control study: Santa Clara County, CA, 1981-1983 Estimated chlorinated tap water consumption, mean maternal TTHM level, showering/bathing exposure at residence during first trimester Congenital cardiac anomalies Following reanalysis, no association between cardiac anomalies and TTHM level were observed. Aschengrau et al. 1989 Case-control study in Massachusetts, 1976-1978 Source of water and exposure to metals and other contaminants Spontaneous abortion A statistically significantly association was detected between surface water source and frequency of spontaneous abortion. Reviews/Meta-analyses Hwang and Jakkola 2003 Review and meta-analysis of 5 studies Compared DBP levels, source of water, chlorine residual, color (high/low), and 2 types of disinfection: chlorination and chloramination Birth defects (respiratory system, urinary system, neural tube defects, cardiac, oral cleft) The meta-analysis supports an association between exposure to chlorination by-products and the risk of any birth defect, particularly the risk of neural tube defects and urinary system defects. Bove et al. 2002 Qualitative review of 14 studies Examined THM levels. Compared drinking water source and type of water treatment Birth defects, small for gestational age, low birth weight, preterm delivery, spontaneous abortion, fetal death Review found the studies of THMs and adverse birth outcomes provide moderate evidence for associations with small for gestational age, neural tube defects, and spontaneous abortions. Authors felt risks may have been underestimated and exposure-response relationships distorted due to exposure misclassification. Graves et al. 2001 Review of toxicological and epidemiological studies using a weight of evidence approach Examined water consumption, duration of exposure, THM levels, HAA levels, and other contaminants. Compared source of water, water treatment, water color (high/low), etc Low birth weight, preterm delivery, small for gestational age, intrauterine growth retardation, specific birth defects, neonatal death, decreased fertility, fetal resorption, and other effects Weight of evidence suggested positive association with DBP exposure for growth retardation such as small for gestational age or intrauterine growth retardation and urinary tract defects. Review found no support for DBP exposure and low birth weight, preterm delivery, some specific birth defects, and neonatal death, and inconsistent findings for all birth defects, all central nervous system defects, neural tube defects, spontaneous abortion, and stillbirth. Villanueva et al. 2001 Qualitative review of 14 reproductive and developmental health effect studies Compared exposure to TTHM levels, mutagenic drinking water, water consumption, source water, types of disinfection (chlorination and chloramination), and residence times Spontaneous abortion, low birth weight, small for gestational age, neural tube defects, other reproductive and developmental outcomes Review found positive associations between increased spontaneous abortion, low birth weight, small for gestational age, and neural tube defects and drinking chlorinated water in most studies, although not always with statistical significance. Nieuwenhuijsen et al. 2000 Qualitative review of numerous toxicological and epidemiological studies Examined levels of various DBPs, water consumption, and duration of exposure. Compared water color, water treatment, source of water, etc Low birth weight, preterm delivery, spontaneous abortions, stillbirth, birth defects, etc The review supports some evidence of association between THMs and low birth weight, but inconclusive. Review found no evidence of association between THMs and preterm delivery, and that associations for other outcomes (spontaneous abortions, stillbirth, and birth defects) were weak but gaining weight. Reif et al. 2000 Qualitative reviews of numerous epidemiological studies Compared source of water supply and methods of disinfection. Estimated TTHM levels Birth weight, low birth weight, intrauterine growth retardation, small for gestational age, preterm deliver, somatic parameters, neonatal jaundice, spontaneous abortion, stillbirth, developmental anomalies Weight of evidence suggested DBPs are reproductive toxicants in humans under appropriate exposure conditions. The review reports findings between TTHMs and effects on fetal growth, fetal viability, and congenital anomalies as inconsistent. Reviewers felt data are at the stage of hazard identification and did not suggest a dose-response pattern of increasing risk with increasing TTHM concentration. WHO 2000 Qualitative reviews of various studies in Finland, U.S., and Canada Various exposures to THMs Various reproductive and developmental effects Review found some support for an association between increased risks of neural tube defects and miscarriage and THM exposure. Other associations have been observed, but the authors believed insufficient data exist to assess any of these associations. Craun, ed. 1998 Qualitative review of 10 studies, focus on California cohort study Examined THM levels and water consumption, and compared source of water and water treatment (chlorine, chloramines, chlorine dioxide) Stillbirth, neonatal death, spontaneous abortion, low birth weight, preterm delivery, intrauterine growth retardation, neonatal jaundice, birth defects Associations between DBPs and various reproductive effects were seen in some epidemiological studies, but the authors felt these results do not provide convincing evidence for a causal relationship between DBPs and reproductive effects. Mills et al. 1998 Qualitative review of 22 studies Examined TTHM levels and water consumption. Compared source of water and 2 types of water treatment (chlorination and chloramination) Various reproductive and developmental effects Review found studies suggest possible increases in adverse reproductive and developmental effects, such as increased spontaneous abortion rates, small for gestational age, and fetal anomalies, but that insufficient evidence exists to establish a causal relationship. Reif et al. 1996 Review of 3 case-control studies and 1 cross-sectional study Examined THM levels at residences, dose consumption, chloroform. Compared source of waters and 2 types of water treatment (chlorination and chloramination) Birth defects (central nervous system, neural tube defects, cardiac, oral cleft, respiratory, urinary tract), spontaneous abortion, low birth weight, growth retardation, preterm delivery, intrauterine growth retardation, stillbirth, neonatal death Studies reviewed suggest that exposure to DBPs may increase intrauterine growth retardation, neural tube defects, major heart defects, and oral cleft defects. Review found epidemiologic evidence supporting associations between exposure to DBPs and adverse pregnancy outcomes to be sparse and to provide an inadequate basis to identify DBPs as a reproductive or developmental hazard. Swan et al. 1992 Qualitative review of 5 studies in Santa Clara County, CA (Deane et al. 1992, Wrensch et al. 1992, Hertz-Picciotto et al. 1992, Windham et al. 1992, Fenster et al. 1992) Compared maternal consumption of residence tap water to bottled water Spontaneous abortion Four of the studies reviewed suggest that women drinking bottled water during the first trimester of pregnancy may have reduced risk of spontaneous abortion relative to drinking tap water. No association seen in the fifth study. Review concluded that if findings are causal and not due to chance or bias, data suggest a 10-50% increase in spontaneous abortion risk for pregnant women drinking tap water over bottled water. ii. Toxicology. To date, the majority of reproductive and developmental toxicology studies have been short term and higher dose. Many of these studies are summarized in a review by Tyl (2000). A summary of this review and of additional studies is provided in the proposed Stage 2 DBPR (USEPA 2003a). Individual DBP supporting documents evaluate and assess additional studies as well (USEPA 2000b; USEPA 2000c; USEPA 2001a; USEPA 2001b; USEPA 2003b; USEPA 2005b; USEPA 2005c; USEPA 2005d; USEPA 2005e; USEPA 2005k). A number of recent studies have been published that include in vivo and in vitro assays to address mechanism of action. Overall, reproductive and developmental toxicology studies indicate a possible reproductive/developmental health hazard although they are preliminary in nature for the majority of DBPs, and the dose-response characteristics of most DBPs have not been quantified. Some of the reproductive effects of DCAA were quantified as part of the RfD development process, and impacts of DCAA on testicular structure are one of the critical effects in the study that is the basis of the RfD (USEPA 2003b). A few long term, lower dose studies have been completed. Christian et al. (2002a and 2002b) looked for an association between BDCM and DBAA and reproductive and developmental endpoints. The authors identified a NOAEL and LOAEL of 50 ppm and 150 ppm, respectively, based on delayed sexual maturation for BDCM and a NOAEL and LOAEL of 50 ppm and 250 ppm based on abnormal spermatogenesis for DBAA. The authors concluded that similar effects in humans would only be seen at levels many orders of magnitude higher than that of current drinking water levels. As discussed in more detail in the proposal, EPA believes that because of key methodological differences indicated as being important in other studies (Bielmeier et al. 2001; Bielmeier et al. 2004; Kaydos et al. 2004; Klinefelter et al. 2001; Klinefelter et al. 2004), definitive conclusions regarding BDCM and DBAA cannot be drawn. Other multi-generation research underway includes a study on BCAA, but this research is not yet published. Biological plausibility for the effects observed in reproductive and developmental epidemiological studies has been demonstrated through various toxicological studies on some individual DBPs (e.g., Bielmeier et al. 2001; Bielmeier et al. 2004; Narotsky et al. 1992; Chen et al. 2003; Chen et al. 2004). Some of these studies were conducted at high doses, but similarity of effects observed between toxicology studies and epidemiology studies strengthens the weight of evidence for a possible association between adverse reproductive and developmental health effects and exposure to chlorinated surface water. c. Conclusions. EPA's weight of evidence evaluation of the best available science on carcinogenicity and reproductive and developmental effects, in conjunction with the widespread exposure to DBPs, supports the incremental regulatory changes in today's rule that target lowering DBPs and providing equitable public health protection. EPA believes that the cancer epidemiology and toxicology literature provide important information that contributes to the weight of evidence for potential health risks from exposure to chlorinated drinking water. At this time, the cancer epidemiology studies support a potential association between exposure to chlorinated drinking water and cancer, but evidence is insufficient to establish a causal relationship. The epidemiological evidence for an association between DBP exposure and colon and rectal cancers is not as consistent as it is for bladder cancer, although similarity of effects reported in animal toxicity and human epidemiology studies strengthens the evidence for an association with colon and rectal cancers. EPA believes that the overall cancer epidemiology and toxicology data support the decision to pursue additional DBP control measures as reflected in the Stage 2 DBPR. Based on the weight of evidence evaluation of the reproductive and developmental epidemiology data, EPA concludes that a causal link between adverse reproductive or developmental health effects and exposure to chlorinated drinking water or DBPs has not been established, but that there is a potential association. Despite inconsistent findings across studies, some recent studies continue to suggest associations between DBP exposure and various adverse reproductive and developmental effects. In addition, data from a number of toxicology studies, although the majority of them were conducted using high doses, demonstrate biological plausibility for some of the effects observed in epidemiology studies. EPA concludes that no dose-response relationship or causal link has been established between exposure to chlorinated drinking water or disinfection byproducts and adverse developmental or reproductive health effects. EPA's evaluation of the best available studies, particularly epidemiology studies is that they do not support a conclusion at this time as to whether exposure to chlorinated drinking water or disinfection byproducts causes adverse developmental and reproductive health effects, but do provide an indication of a potential health concern that warrants incremental regulatory action beyond the Stage 1 DBPR. D. DBP Occurrence and DBP Control New information on the occurrence of DBPs in distribution systems raises issues about the protection provided by the Stage 1 DBPR. This section presents new occurrence and treatment information used to identify key issues and to support the development of the Stage 2 DBPR. For a more detailed discussion see the proposed Stage 2 DBPR (USEPA 2003a). For additional information on occurrence of regulated and nonregulated DBPs, see the Occurrence Assessment for the Final Stage 2 Disinfectants and Disinfection Byproducts Rule (USEPA 2005f). 1. Occurrence EPA, along with the M-DBP Advisory Committee, collected, developed, and evaluated new information that became available after the Stage 1 DBPR was published. The Information Collection Rule (ICR) (USEPA 1996) provided new field data on DBP exposure for large water systems and new study data on the effectiveness of several DBP control technologies. The unprecedented amount of information collected under the ICR was supplemented by a survey conducted by the National Rural Water Association, data provided by various States, the Water Utility Database (which contains data collected by the American Water Works Association), and ICR Supplemental Surveys for small and medium water systems. After analyzing the DBP occurrence data, EPA and the Advisory Committee reached three significant conclusions that in part led the Advisory Committee to recommend further control of DBPs in public water systems. First, the data from the Information Collection Rule showed that the RAA compliance calculation under the Stage 1 DBPR allows elevated TTHM or HAA5 levels to regularly occur at some locations in the distribution system while the overall average of TTHM or HAA5 levels at all DBP monitoring locations is below the MCLs of the Stage 1 DBPR. Customers served at those sampling locations with DBP levels that are regularly above 0.080 mg/L TTHM and 0.060 mg/L HAA5 experience higher exposure compared to customers served at locations where these levels are consistently met. Second, the new data demonstrated that DBP levels in single samples can be substantially above 0.080 mg/L TTHM and 0.060 mg/L HAA5. Some customers receive drinking water with concentrations of TTHM and HAA5 up to 75% above 0.080 mg/L and 0.060 mg/L, respectively, even when their water system is in compliance with the Stage 1 DBPR. Some studies support an association between acute exposure to DBPs and potential adverse reproductive and developmental health effects (see Section III.C for more detail). Third, the data from the Information Collection Rule revealed that the highest TTHM and HAA5 levels can occur at any monitoring site in the distribution system. In fact, the highest concentrations did not occur at the maximum residence time locations in more than 50% of all ICR samples. The fact that the locations with the highest DBP levels vary in different public water systems indicates that the Stage 1 DBPR monitoring may not accurately represent the high DBP concentrations that actually exist in distribution systems, and that additional monitoring is needed to identify distribution system locations with elevated DBP levels. These data showed that efforts beyond the Stage 1 DBPR are needed to provide more equitable protection from DBP exposure across the entire distribution system. The incremental regulatory changes made under the Stage 2 DBPR meet this need by reevaluating the locations of DBP monitoring sites and addressing high DBP concentrations that occur at particular locations or in single samples within systems in compliance. 2. Treatment The analysis of the new treatment study data confirmed that certain technologies are effective at reducing DBP concentrations. Bench- and pilot-scale studies for granular activated carbon (GAC) and membrane technologies required by the Information Collection Rule provided information on the effectiveness of the two technologies. Other studies found UV light to be highly effective for inactivating Cryptosporidium and Giardia at low doses without promoting the formation of DBPs (Malley et al. 1996; Zheng et al. 1999). This new treatment information adds to the treatment options available to utilities for controlling DBPs beyond the requirements of the Stage 1 DBPR. E. Conclusions for Regulatory Action After extensive analysis of available data and rule options considered by the Advisory Committee and review of public comments on the proposed Stage 2 DBPR (USEPA, 2003a), EPA is finalizing a Stage 2 DBPR control strategy consistent with the key elements of the Agreement in Principle signed in September 2000 by the participants in the Stage 2 M-DBP Advisory Committee. EPA believes that exposure to chlorinated drinking water may be associated with cancer, reproductive, and developmental health risks. EPA determined that the risk-targeting measures recommended in the Agreement in Principle will require only those systems with the greatest risk to make treatment and operational changes and will maintain simultaneous protection from potential health concerns from DBPs and microbial contaminants. EPA has carefully evaluated and expanded upon the recommendations of the Advisory Committee and public comments to develop today's rule. EPA also made simplifications where possible to minimize complications for public water systems as they transition to compliance with the Stage 2 DBPR while expanding public health protection. The requirements of the Stage 2 DBPR are described in detail in Section IV of this preamble. IV. Explanation of Today's Action A. MCLGs MCLGs are set at concentration levels at which no known or anticipated adverse health effects occur, allowing for an adequate margin of safety. Establishment of an MCLG for each specific contaminant is based on the available evidence of carcinogenicity or noncancer adverse health effects from drinking water exposure using EPA's guidelines for risk assessment. MCLGs are developed to ensure they are protective of the entire population. Today's rule provides MCLGs for chloroform and two haloacetic acids, monochloroacetic acid (MCAA) and trichloroacetic acid (TCAA). 1. Chloroform MCLG a. Today's rule. The final MCLG for chloroform is 0.07 mg/L. The MCLG was calculated using toxicological evidence that the carcinogenic effects of chloroform are due to sustained tissue toxicity. EPA is not changing the other THM MCLGs finalized in the Stage 1 DBPR. b. Background and analysis. The MCLG for chloroform is unchanged from the proposal. The MCLG is calculated using a reference dose (RfD) of 0.01 mg/kg/day and an adult tap water consumption of 2 L per day for a 70 kg adult. A relative source contribution (RSC) of 20% was used in accordance with Office of Water's current approach for deriving RSC through consideration of data that indicate that other routes and sources of exposure may potentially contribute substantially to the overall exposure to chloroform. See the proposed Stage 2 DBPR (USEPA 2003a) for a detailed discussion of the chloroform MCLG. ER04JA06.003 Based on an analysis of the available scientific data on chloroform, EPA believes that the chloroform dose-response is nonlinear and that chloroform is likely to be carcinogenic only under high exposure conditions (USEPA 2001a). This assessment is supported by the principles of the 1999 EPA Proposed Guidelines for Carcinogen Risk Assessment (USEPA 1999a) and reconfirmed by the 2005 final Cancer Guidelines (USEPA 2005i). The science in support of a nonlinear approach for estimating the carcinogenicity of chloroform was affirmed by the Chloroform Risk Assessment Review Subcommittee of the EPA SAB Executive Committee (USEPA 2000d). Since the nonzero MCLG is based on a mode of action consideration specific to chloroform, it does not affect the MCLGs of other trihalomethanes. c. Summary of major comments. EPA received many comments in support of the proposed MCLG calculation for chloroform, although some commenters disagreed with a non-zero MCLG. At this time, based on an analysis of all the available scientific data on chloroform, EPA concludes that chloroform is likely to be carcinogenic to humans only under high exposure conditions that lead to cytotoxicity and regenerative hyperplasia and that chloroform is not likely to be carcinogenic to humans under conditions that do not cause cytotoxicity and cell regeneration (USEPA 2001a). Therefore, the dose-response is nonlinear, and the MCLG is set at 0.07 mg/L. This conclusion has been reviewed by the SAB (USEPA 2000d), who agree that nonlinear approach is most appropriate for the risk assessment of chloroform; it also remains consistent with the principles of the 1999 EPA Proposed Guidelines for Carcinogenic Risk Assessment (USEPA 1999a) and the final Cancer Guidelines ( USEPA 2005i), which allow for nonlinear extrapolation. EPA also received some comments requesting a combined MCLG for THMs or HAAs. This is not appropriate because these different chemicals have different health effects. 2. HAA MCLGs: TCAA and MCAA a. Today's rule. Today's rule finalizes the proposed Stage 2 MCLG for TCAA of 0.02 mg/L (USEPA 2003a) and sets an MCLG for MCAA of 0.07 mg/L. EPA is not changing the other HAA MCLGs finalized in the Stage 1 DBPR (USEPA 1998a). b. Background and analysis. The Stage 1 DBPR included an MCLG for TCAA of 0.03 mg/L and did not include an MCLG for MCAA (USEPA 1998a). Based on toxicological data published after the Stage 1 DBPR, EPA proposed new MCLGs for TCAA and MCAA of 0.02 mg/L and 0.03 mg/L, respectively, in the Stage 2 proposal (USEPA 2003a). The proposed TCAA MCLG and its supporting analysis is being finalized unchanged in today's final rule. The MCLG calculation for MCAA is revised in this final rule, based on a new reference dose, as discussed later. See the proposed Stage 2 DBPR (USEPA 2003a) for a detailed discussion of the calculation of the MCLGs. TCAA. The MCLG for TCAA was calculated based on the RfD of 0.03 mg/kg/day using a 70 kg adult body weight, a 2 L/day drinking water intake, and a relative source contribution of 20%. An additional tenfold risk management factor has been applied to account for the possible carcinogenicity of TCAA. This approach is consistent with EPA policy. TCAA induces liver tumors in mice (Ferreira-Gonzalez et al. 1995; Pereira 1996; Pereira and Phelps 1996; Tao et al. 1996; Latendresse and Pereira 1997; Pereira et al. 1997) but not in rats (DeAngelo et al. 1997). Much of the recent data on the carcinogenicity of TCAA have focused on examining the carcinogenic mode(s) of action. However, at this time, neither the bioassay nor the mechanistic data are sufficient to support the development of a slope factor from which to quantify the cancer risk. ER04JA06.000 The chronic bioassay for TCAA by DeAngelo et al. (1997) was selected as the critical study for the development of the RfD. In this chronic drinking water study, a dose-response was noted for several endpoints and both a LOAEL and NOAEL were determined. The data are consistent with the findings in both the Pereira (1996) chronic drinking water study and the Mather et al. (1990) subchronic drinking water study. The RfD of 0.03 mg/kg/day is based on the NOAEL of 32.5 mg/kg/day for liver histopathological changes in rats (DeAngelo et al. 1997). A composite uncertainty factor of 1000 was applied in the RfD determination. A default uncertainty factor of 10 was applied to the RfD to account for extrapolation from an animal study because data to quantify rat-to-human differences in toxicokinetics or toxicodynamics are not available. The default uncertainty factor of 10 was used to account for human variability in the absence of data on differences in human susceptibility. Although subchronic and chronic studies of TCAA have been reported for multiple species, many studies have focused on liver lesions and a full evaluation of a wide range of potential target organs has not been conducted in two different species. In addition, there has been no multi-generation study of reproductive toxicity and the data from teratology studies in rats provide LOAEL values but no NOAEL for developmental toxicity. Thus, an additional uncertainty factor of 10 was used to account for database insufficiencies. The MCLG calculation also includes a relative source contribution (RSC) of 20%. The RSC was derived consistent with Office of Water's current approach for deriving RSC. In addition to disinfected water, foods are expected to contribute to daily exposure to TCAA (Raymer et al. 2001, 2004; Reimann et al. 1996). Some of the TCAA in foods comes from cleaning and cooking foods in chlorinated water. Additional TCAA is found in some foods because of the widespread use of chlorine as a sanitizing agent in the food industry (USFDA 1994). EPA was not able to identify any dietary sur [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%3A06-3. Public record. Not legal advice.