[Federal Register Volume 63, Number 61 (Tuesday, March 31, 1998)]
[Proposed Rules]
[Pages 15674-15692]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-8215]


      

[[Page 15673]]

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Part IV





Environmental Protection Agency





_______________________________________________________________________



40 CFR Parts 141 and 142



National Primary Drinking Water Regulations: Disinfectants and 
Disinfection Byproducts Notice of Data Availability; Proposed Rule

  Federal Register / Vol. 63, No. 61 / Tuesday, March 31, 1998 / 
Proposed Rules  

[[Page 15674]]



ENVIRONMENTAL PROTECTION AGENCY

40 CFR Parts 141 and 142

[WH-FRL-5988-7]


National Primary Drinking Water Regulations: Disinfectants and 
Disinfection Byproducts Notice of Data Availability

AGENCY: U.S. Environmental Protection Agency (USEPA).

ACTION: Notice of data availability; request for comments.

-----------------------------------------------------------------------

SUMMARY: In 1994 USEPA proposed a Stage 1 Disinfectants/Disinfection 
Byproducts Rule (D/DBP) to reduce the level of exposure from 
disinfectants and disinfection byproducts (DBPs) in drinking water 
(USEPA, 1994a). This Notice of Data Availability summarizes the 1994 
proposal and a subsequent Notice of Data Availability in 1997 (USEPA, 
1997a); describes new data that the Agency has obtained and analyses 
that have been completed since the 1997 Notice of Data Availability; 
requests comments on the regulatory implications that flow from the new 
data and analyses; and requests comments on several issues related to 
the simultaneous compliance with the Stage 1 DBP Rule and the Lead and 
Copper Rule. USEPA solicits comment on all aspects of this Notice and 
the supporting record. The Agency also solicits additional data and 
information that may be relevant to the issues discussed in the Notice.
    The Stage 1 D/DBP rule would apply to community water systems and 
nontransient noncommunity water systems that treat their water with a 
chemical disinfectant for either primary or residual treatment. In 
addition, certain requirements for chlorine dioxide would apply to 
transient noncommunity water systems because of the short-term health 
effects from high levels of chlorine dioxide.
    Key issues related to the Stage 1 D/DBP rule that are addressed in 
this Notice include the establishment of Maximum Contaminant Level 
Goals for chloroform, dichloroacetic acid, chlorite, and bromate and 
the Maximum Residual Disinfectant Level Goal for chlorine dioxide.

DATES: Comments should be postmarked or delivered by hand on or before 
April 30, 1998. Comments must be received or post-marked by midnight 
April 30, 1998.

ADDRESSES: Send written comments to DBP NODA Docket Clerk, Water Docket 
(MC-4101); U.S. Environmental Protection Agency; 401 M Street, SW., 
Washington, DC 20460. Comments may be hand-delivered to the Water 
Docket, U.S. Environmental Protection Agency; 401 M Street, SW., East 
Tower Basement, Washington, DC 20460. Comments may be submitted 
electronically to [email protected].

FOR FURTHER INFORMATION CONTACT: For general information contact, the 
Safe Drinking Water Hotline, Telephone (800) 426-4791. The Safe 
Drinking Water Hotline is open Monday through Friday, excluding Federal 
holidays, from 9:00 a.m. to 5:30 p.m. Eastern Time. For technical 
inquiries, contact Dr. Vicki Dellarco, Office of Science and Technology 
(MC 4304) or Mike Cox, Office of Ground Water and Drinking Water (MC 
4607), U.S. Environmental Protection Agency, 401 M Street SW., 
Washington DC 20460; telephone (202) 260-7336 (Dellarco) or (202) 260-
1445 (Cox).

SUPPLEMENTARY INFORMATION:
    Regulated entities. Entities potentially regulated by the Stage 1 
D/DBP rule are public water systems that add a disinfectant or oxidant. 
Regulated categories and entities include:

------------------------------------------------------------------------
                                                Examples of regulated   
                 Category                             entities          
------------------------------------------------------------------------
Public Water System.......................  Community and nontransient  
                                             noncommunity water systems 
                                             that add a disinfectant or 
                                             oxidant.                   
State Governments.........................  State government offices    
                                             that regulate drinking     
                                             water.                     
------------------------------------------------------------------------

    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 this table could also be regulated. To determine whether 
your facility may be regulated by this action, you should carefully 
examine the applicability criteria in Sec. 141.130 of the proposed rule 
(USEPA, 1994a). If you have questions regarding the applicability of 
this action to a particular entity, contact one of the persons listed 
in the preceding FOR FURTHER INFORMATION CONTACT section.
    Additional Information for Commenters. Please submit an original 
and three copies of your comments and enclosures (including 
references). The Agency requests that commenters follow the following 
format: Type or print comments in ink, and cite, where possible, the 
paragraph(s) in this Notice to which each comment refers. Commenters 
should use a separate paragraph for each method or issue discussed. 
Electronic comments must be submitted as a WP5.1 or WP6.1 file or as an 
ASCII file avoiding the use of special characters. Comments and data 
will also be accepted on disks in WordPerfect in 5.1 or WP6.1 or ASCII 
file format. Electronic comments on this Notice may be filed online at 
many Federal Depository Libraries. Commenters who want EPA to 
acknowledge receipt of their comments should include a self-addressed, 
stamped envelope. No facsimiles (faxes) will be accepted.
    Availability of Record. The record for this Notice, which includes 
supporting documentation as well as printed, paper versions of 
electronic comments, is available for inspection from 9 to 4 p.m. 
(Eastern Time), Monday through Friday, excluding legal holidays, at the 
Water Docket, U.S. EPA Headquarters, 401 M. St., S.W., East Tower 
Basement, Washington, D.C. 20460. For access to docket materials, 
please call 202/260-3027 to schedule an appointment.

Abbreviations Used in This Notice

AWWA: American Water Works Association
AWWARF: AWWA Research Foundation
BAT: Best Available Technology
BDCM: Bromodichloromethane
CMA: Chemical Manufacturers Association
CWS: Community Water System
DBCM: Dibromochloromethane
DBP: Disinfection Byproducts
D/DBP: Disinfectants and Disinfection Byproducts
DCA: Dichloroacetic Acid
ED10: Maximum likelihood estimate on a dose associated with 
10% extra risk
EPA: United States Environmental Protection Agency
ESWTR: Enhanced Surface Water Treatment Rule
FACA: Federal Advisory Committee Act
GAC: Granular Activated Carbon
HAA5: Haloacetic Acids (five)
HAN: Haloacetonitrile
ICR: Information Collection Rule
ILSI: International Life Sciences Institute
IESTWR: Interim Enhanced Surface Water Treatment Rule
IRFA: Initial Regulatory Flexibility Analysis
LCR: Lead and Cooper Rule
LED10: Lower 95% confidence limit on a dose associated with 
10% extra risk
LMS: Linear Multistage Model
LOAEL: Lowest Observed Adverse Effect Level
LTESTWR: Long-Term Enhanced Surface Water Treatment Rule

[[Page 15675]]

MCL: Maximum Contaminant Level
MCLG: Maximum Contaminant Level Goal
M-DBP: Microbial and Disinfectants/Disinfection Byproducts
mg/L: Milligrams per liter
MoE: Margin of Exposure
MRDL: Maximum Residual Disinfectant Level
MRDLG: Maximum Residual Disinfectant Level Goal
MTD: Maximum Tolerated Dose
NIPDWR: National Interim Primary Drinking Water Regulation
NOAEL: No Observed Adverse Effect Level
NODA: Notice of Data Availability
NPDWR: National Primary Drinking Water Regulation
NTNCWS: Nontransient Noncommunity Water System
NTP: National Toxicology Program
PAR: Population Attributable Risk
PQL: Practical Quantitation Limit
PWS: Public Water System
q1 *: Cancer Potency Factor
RFA: Regulatory Flexibility Act
RfD: Reference Dose
RIA: Regulatory Impact Analysis
RSC: Relative Source Contribution
SAB: Science Advisory Board
SBREFA: Small Business Regulatory Enforcement Fairness Act
SDWA: Safe Drinking Water Act, or the ``Act,'' as amended in 1986 and 
1996
SWTR: Surface Water Treatment Rule
TCA: Trichloroacetic Acid
TOC: Total Organic Carbon
TTHM: Total Trihalomethanes
TWG: Technical Working Group

Table of Contents

I. Introduction and Background
    A. 1979 Total Trihalomethane MCL
    B. Statutory Authority
    C. Regulatory Negotiation Process
    D. Overview of 1994 DBP Proposal
    1. MCLGs/MCLs/MRDLGs/MRDLs
    2. Best Available Technologies
    3. Treatment Technique
    4. Preoxidation (Predisinfection) Credit
    5. Analytical Methods
    6. Effect on Small Public Water Systems
    E. Formation of 1997 Federal Advisory Committee
II. Significant New Epidemiology Information for the Stage 1 
Disinfectants and Disinfection Byproducts Rule
    A. Epidemiological Associations Between the Exposure to DBPs in 
Chlorinated Water and Cancer
    1. Assessment of the Morris et al. (1992) Meta-Analysis
    a. Poole Report
    b. EPA's Evaluation of Poole Report
    c. Peer Review of Poole Report and EPA's Evaluation
    2. New Cancer Epidemiology Studies
    3. Quantitative Risk Estimation for Cancers From Exposure to 
Chlorinated Water
    4. Peer-Review of Quantitative Risk Estimates
    5. Summary of Key Observations
    6. Requests for Comments
    B. Epidemiological Associations Between Exposure to DBPs in 
Chlorinated Water and Adverse Reproductive and Developmental Effects
    1. EPA Panel Report and Recommendations for Conducting 
Epidemiological Research on Possible Reproductive and Developmental 
Effects of Exposure to Disinfected Drinking Water
    2. New Reproductive Epidemiology Studies
    3. Summary of Key Observations
    4. Request for Comments
III. Significant New Toxicological Information for the Stage 1 
Disinfectants and Disinfection Byproducts
    A. Chlorite and Chlorine Dioxide
    1. 1997 CMA Two-Generation Reproduction Rat Study
    2. External Peer Review of the CMA Study
    3. MCLG for Chlorite: EPA's Reassessment of the Noncancer Risk
    4. MRDLG for Chlorine Dioxide: EPA's Reassessment of the 
Noncancer Risk
    5. External Peer Review of EPA's Reassessment
    6. Summary of Key Observations
    7. Request for Comments
    B. Trihalomethanes
    1. 1997 International Life Sciences Institute Expert Panel 
Conclusions for Chloroform
    2. MCLG for Chloroform: EPA's Reassessment of the Cancer Risk
    a. Weight of the Evidence and Understanding of the Mode of 
Carcinogenic Action
    b. Dose-Response Assessment
    3. External Peer Review of EPA's Reassessment
    4. Summary of Key Observations
    5. Requests for Comments
    C. Haloacetic Acids
    1. 1997 International Life Sciences Institute Expert Panel 
Conclusions for Dichloroacetic Acid (DCA)
    2. MCLG for DCA: EPA's Reassessment of the Cancer Hazard
    3. External Peer Review of EPA's Reassessment
    4. Summary of Key Observations
    5. Requests for Comments
    D. Bromate
    1. 1998 EPA Rodent Cancer Bioassay
    2. MCLG for Bromate: EPA's Reassessment of the Cancer Risk
    3. External Peer Review of EPA's Reassessment
    4. Summary of Key Observations
    5. Requests for Comments
IV. Simultaneous Compliance Considerations: D/DBP Stage 1 Enhanced 
Coagulation Requirements and the Lead and Copper Rule
V. Compliance with Current Regulations
VI. Conclusions
VII. References

I. Introduction and Background

A. 1979 Total Trihalomethane MCL

    USEPA set an interim maximum contaminant level (MCL) for total 
trihalomethanes (TTHMs) of 0.10 mg/L as an annual average in November 
1979 (USEPA, 1979). There are four trihalomethanes (chloroform, 
bromodichloromethane, chlorodibromomethane, and bromoform). The interim 
TTHM standard applies to any PWS (surface water and/or ground water) 
serving at least 10,000 people that adds a disinfectant to the drinking 
water during any part of the treatment process. At their discretion, 
States may extend coverage to smaller PWSs. However, most States have 
not exercised this option. About 80 percent of the PWSs, serving 
populations of less than 10,000, are served by ground water that is 
generally low in THM precursor content (USEPA, 1979) and which would be 
expected to have low TTHM levels even if they disinfect.

B. Statutory Authority

    In 1996, Congress reauthorized the Safe Drinking Water Act. Several 
of the 1986 provisions were renumbered and augmented with additional 
language, while other sections mandate new drinking water requirements. 
As part of the 1996 amendments to the Safe Drinking Water Act, USEPA's 
general authority to set a Maximum Contaminant Level Goal (MCLG) and a 
National Primary Drinking Water Regulation (NPDWR) was modified to 
apply to contaminants that ``may have an adverse effect on the health 
of persons'', that are ``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' (1986 SDWA Section 1412 
(b)(3)(A) stricken and amended with 1412(b)(1)(A)).
    The Act also requires that at the same time USEPA publishes an 
MCLG, which is a non-enforceable health goal, it also must publish a 
NPDWR that specifies either a maximum contaminant level (MCL) or 
treatment technique (Sections 1401(1), 1412(a)(3), and 1412 (b)(4)B)). 
USEPA is authorized to promulgate a NPDWR ``that requires the use of a 
treatment technique in lieu of establishing a MCL,'' if the Agency 
finds that ``it is not economically or technologically feasible to 
ascertain the level of the contaminant'' (1412(b)(7)(A)).
    The 1996 Amendments also require USEPA to promulgate a Stage 1 
disinfectants/disinfection byproducts (D/DBP) rule by November 1998. In

[[Page 15676]]

addition, the 1996 Amendments require USEPA to promulgate a Stage 2 D/
DBP rule by May 2002 (Section 1412(b)(2)(C)).

C. Regulatory Negotiation Process

    In 1992 USEPA initiated a negotiated rulemaking to develop a D/DBP 
rule. The negotiators included representatives of State and local 
health and regulatory agencies, public water systems, elected 
officials, consumer groups and environmental groups. The Committee met 
from November 1992 through June 1993.
    Early in the process, the negotiators agreed that large amounts of 
information necessary to understand how to optimize the use of 
disinfectants to concurrently minimize microbial and DBP risk on a 
plant-specific basis were unavailable. Nevertheless, the Committee 
agreed that USEPA should propose a D/DBP rule to extend coverage to all 
community and nontransient noncommunity water systems that use 
disinfectants. This rule proposed to reduce the current TTHM MCL, 
regulate additional disinfection byproducts, set limits for the use of 
disinfectants, and reduce the level of organic compounds from the 
source water that may react with disinfectants to form byproducts.
    One of the major goals addressed by the Committee was to develop an 
approach that would reduce the level of exposure from disinfectants and 
DBPs without undermining the control of microbial pathogens. The 
intention was to ensure that drinking water is microbiologically safe 
at the limits set for disinfectants and DBPs and that these chemicals 
do not pose an unacceptable risk at these limits.
    Following months of intensive discussions and technical analysis, 
the Committee recommended the development of three sets of rules: a 
staged D/DBP Rule (proposal: 59 FR 38668, July 29, 1994), an 
``interim'' Enhanced Surface Water Treatment Rule (IESWTR) (proposal: 
59 FR 38832, July 29, 1994), and an Information Collection Rule (final 
61 FR 24354, May 14, 1996). The IESWTR would only apply to systems 
serving 10,000 people or more. The Committee agreed that a ``long-
term'' ESWTR (LTESWTR) would be needed for systems serving fewer than 
10,000 people when the results of more research and water quality 
monitoring became available. The LTESWTR could also include additional 
refinements for larger systems.

D. Overview of 1994 DBP Proposal

    The proposed D/DBP Stage 1 rule addressed a number of complex and 
interrelated drinking water issues. The proposal attempted to balance 
the control of health risks from compounds formed during drinking water 
disinfection against the risks from microbial organisms (such as 
Giardia lamblia, Cryptosporidium, bacteria, and viruses) to be 
controlled by the IESWTR.
    The proposed Stage 1 D/DBP rule applied to all community water 
systems (CWSs) and nontransient noncommunity water systems (NTNCWSs) 
that treat their water with a chemical disinfectant for either primary 
or residual treatment. In addition, certain requirements for chlorine 
dioxide would apply to transient noncommunity water systems because of 
the short-term health effects from high levels of chlorine dioxide. 
Following is a summary of key components of the 1994 proposed Stage 1 
D/DBP rule.
1. MCLGs/MCLs/MRDLGs/MRDLs
    EPA proposed MCLGs of zero for chloroform, bromodichloromethane, 
bromoform, bromate, and dichloroacetic acid and MCLGs of 0.06 mg/L for 
dibromochloromethane, 0.3 mg/L for trichloroacetic acid, 0.04 mg/L for 
chloral hydrate, and 0.08 mg/L for chlorite. In addition, EPA proposed 
to lower the MCL for TTHMs from 0.10 to 0.080 mg/L and added an MCL for 
five haloacetic acids (i.e., the sum of the concentrations of mono-, 
di-, and trichloroacetic acids and mono-and dibromoacetic acids) of 
0.060 mg/L. EPA also, for the first time, proposed MCLs for two 
inorganic DBPs: 0.010 mg/L for bromate and 1.0 mg/L for chlorite.
    In addition to proposing MCLGs and MCLs for several DBPs, EPA 
proposed maximum residual disinfectant level goals (MRDLGs) of 4 mg/L 
for chlorine and chloramines and 0.3 mg/L for chlorine dioxide. The 
Agency also proposed maximum residual disinfectant levels (MRDLs) for 
chlorine and chloramines of 4.0 mg/L, and 0.8 mg/L for chlorine 
dioxide. MRDLs protect public health by setting limits on the level of 
residual disinfectants in the distribution system. MRDLs are similar in 
concept to MCLs--MCLs set limits on contaminants and MRDLs set limits 
on residual disinfectants in the distribution system. MRDLs, like MCLs, 
are enforceable, while MRDLGs, like MCLGs, are not enforceable.
2. Best Available Technologies
    EPA identified the best available technology (BAT) for achieving 
compliance with the MCLs for both TTHMs and HAA5 as enhanced 
coagulation or treatment with granular activated carbon with a ten 
minute empty bed contact time and 180 day reactivation frequency 
(GAC10), with chlorine as the primary and residual disinfectant. The 
BAT for achieving compliance with the MCL for bromate was control of 
ozone treatment process to reduce formation of bromate. The BAT for 
achieving compliance with the chlorite MCL was control of precursor 
removal treatment processes to reduce disinfectant demand, and control 
of chlorine dioxide treatment processes to reduce disinfectant levels. 
EPA identified BAT for achieving compliance with the MRDL for chlorine, 
chloramine, and chlorine dioxide as control of precursor removal 
treatment processes to reduce disinfectant demand, and control of 
disinfection treatment processes to reduce disinfectant levels.
3. Treatment Technique
    EPA proposed a treatment technique that would require surface water 
systems and groundwater systems under the direct influence of surface 
water that use conventional treatment or precipitative softening to 
remove DBP precursors by enhanced coagulation or enhanced softening. A 
system would be required to remove a certain percentage of total 
organic carbon (TOC) (based on raw water quality) prior to the point of 
continuous disinfection. EPA also proposed a procedure to be used by a 
PWS not able to meet the percent reduction, to allow them to comply 
with an alternative minimum TOC removal level. Compliance for systems 
required to operate with enhanced coagulation or enhanced softening was 
based on a running annual average, computed quarterly, of normalized 
monthly TOC percent reductions.
4. Preoxidation (Predisinfection) Credit
    The proposed rule did not allow PWSs to take credit for compliance 
with disinfection requirements in the SWTR/IESWTR prior to removing 
required levels of precursors unless they met specified criteria. This 
provision was modified by the 1997 Federal Advisory Committee (see 
below).
5. Analytical Methods
    EPA proposed nine analytical methods (some of which can be used for 
multiple analyses) to ensure compliance with proposed MRDLs for 
chlorine, chloramines, and chlorine dioxide. EPA proposed methods for 
the analysis of TTHMs, HAA5, chlorite, bromate and total organic 
carbon.
6. Effect on Small Public Water Systems
    The Regulatory Flexibility Act (RFA), as amended by the Small 
Business

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Regulatory Enforcement Fairness Act (SBREFA), requires federal 
agencies, in certain circumstances, to consider the economic effect of 
proposed regulations on small entities. The agency must assess the 
economic impact of a proposed rule on small entities if the proposal 
will have a significant economic impact on a substantial number of 
small entities. Under the RFA, 5 U.S.C. 601 et seq., an agency must 
prepare an initial regulatory flexibility analysis (IRFA) describing 
the economic impact of a rule on small entities unless the agency 
certifies that the rule will not have a significant impact.
    In the l994 D/DBP and IESWTR proposals, EPA defined small entities 
as small PWSs--serving 10,000 or fewer persons--for purposes of its 
regulatory flexibility assessments under the RFA. EPA certified that 
the IESWTR will not have a significant impact on a substantial number 
of small entities, and prepared an IRFA for the DBP proposed rule. EPA 
did not, however, specifically solicit comment on that definition. EPA 
will use this same definition of small PWSs in preparing the final RFA 
for the Stage 1 DBP rule. Further, EPA plans to define small entities 
in the same way in all of its future drinking water rulemakings. The 
Agency solicited public comment on this definition in the proposed 
National Primary Drinking Water Regulations: Consumer Confidence 
Reports, 63 FR 7606, at 7620-21, February 13, 1998.

E. Formation of 1997 Federal Advisory Committee

    In May 1996, the Agency initiated a series of public informational 
meetings to exchange information on issues related to microbial and D/
DBP regulations. To help meet the deadlines for the IESWTR and Stage 1 
D/DBP rule established by Congress in the 1996 SDWA Amendments and to 
maximize stakeholder participation, the Agency established the 
Microbial and Disinfectants/Disinfection Byproducts (M-DBP) Advisory 
Committee under the Federal Advisory Committee Act (FACA) on February 
12, 1997, to collect, share, and analyze new information and data, as 
well as to build consensus on the regulatory implications of this new 
information. The Committee consists of 17 members representing USEPA, 
State and local public health and regulatory agencies, local elected 
officials, drinking water suppliers, chemical and equipment 
manufacturers, and public interest groups.
    The Committee met five times, in March through July 1997, to 
discuss issues related to the IESWTR and Stage 1 D/DBP rule. Technical 
support for these discussions was provided by a Technical Work Group 
(TWG) established by the Committee at its first meeting in March 1997. 
The Committee's activities resulted in the collection, development, 
evaluation, and presentation of substantial new data and information 
related to key elements of both proposed rules. The Committee reached 
agreement on the following major issues that were discussed in the 1997 
NODA (USEPA, 1997a): (1) Maintaining the proposed MCLs for TTHMs, HAA5 
and bromate; (2) modifying the enhanced coagulation requirements as 
part of DBP control; (3) including a microbial bench marking/profiling 
to provide a methodology and process by which a PWS and the State, 
working together, assure that there will be no significant reduction in 
microbial protection as the result of modifying disinfection practices 
in order to meet MCLs for TTHM and HAA5; (4) credit for compliance with 
applicable disinfection requirements should continue to be allowed for 
disinfection applied at any point prior to the first customer, 
consistent with the existing Surface Water Treatment Rule; (5) 
modification of the turbidity performance requirements and requirements 
for individual filters; (6) issues related to the MCLG for 
Cryptosporidium; (7) requirements for removal of Cryptosporidium; and 
(8) provision for conducting sanitary surveys.

II. Significant New Epidemiology Information for the Stage 1 
Disinfectant and Disinfection Byproducts Rule

    The preamble to the 1994 proposed rule provided a summary of the 
health criteria documents for the following DBPs: Bromate; chloramines; 
haloacetic acids and chloral hydrate; chlorine; chlorine dioxide, 
chlorite, and chlorate; and trihalomethanes (USEPA, 1994a). The 
information presented in 1994 was used to establish MCLGs and MRDLGs. 
On November 3, 1997, the EPA published a Notice of Data Availability 
(NODA) summarizing new information that the Agency has obtained since 
the 1994 proposed rule (USEPA, 1997a). The following sections briefly 
discuss additional information received and analyzed since the November 
1997 NODA. This new information concerns the following: (1) Recently 
published epidemiology studies examining the relationship between 
exposure to contaminants in chlorinated surface water and adverse 
health outcomes; (2) an assessment of the Morris et. al. (1992) meta-
analysis of the epidemiology studies published prior to 1996; (3) 
recommendations made by an International Life Science Institute (ILSI) 
expert panel on the application of the USEPA Proposed Guidelines for 
Carcinogen Assessment (USEPA, 1996b) to data sets for chloroform and 
dichloroacetic acid; and (4) new laboratory animal studies on bromate 
and chlorite (also applicable to chlorine dioxide risk). This Notice 
presents the conclusions of these supplemental analyses as well as 
their implications for MCLGs, MCLs, MRDLGs, and MRDLs. The new 
documents are included in the Docket for this action.
    As a result of this new information, the EPA requests comment on 
the following: (1) Revisions to estimates of potential cancer cases 
that can be attributed to exposure from DBPs in chlorinated surface 
water (USEPA, 1998a); (2) revisions to the noncancer assessment for 
chlorite and chlorine dioxide (USEPA, 1998b); (3) revisions to the 
cancer quantitative risks for chloroform (USEPA, 1998c); (4) updates on 
the cancer assessment for bromate (USEPA, 1998d); and (5) updates on 
the hazard characterization for dichloroacetic acid (USEPA, 1998e).
    As in 1994, the assessment of public health risks from chlorination 
of drinking water currently relies on inherently difficult and 
incomplete empirical analysis. On one hand, epidemiologic studies of 
the general population are hampered by difficulties of design, scope, 
and sensitivity. On the other hand, uncertainty is involved in using 
the results of high dose animal toxicological studies of a few of the 
numerous byproducts that occur in disinfected drinking water to 
estimate the risk to humans from chronic exposure to low doses of these 
and other byproducts. In addition, such studies of individual 
byproducts cannot characterize the entire mixture of disinfection 
byproducts in drinking water. Nevertheless, while recognizing the 
uncertainties of basing quantitative risk estimates on less than 
comprehensive information regarding overall hazard, EPA believes that 
the weight-of-evidence represented by the available epidemiological and 
toxicological studies on DBPs and chlorinated surface water continues 
to support a hazard concern and a protective public health approach to 
regulation.

A. Epidemiologic Associations Between Exposure to DBPs in Chlorinated 
Water and Cancer

    The preamble to the 1994 proposed rule discussed several cancer 
epidemiology studies that had been conducted over the past 20 years to

[[Page 15678]]

examine the association between exposure to chlorinated water and 
cancer (USEPA, 1994a). At the time of the 1994 proposed rule, there was 
disagreement among the members of the Negotiating Committee on the 
conclusions that could be drawn from these studies. Some members of the 
Committee felt that the cancer epidemiology data, taken in conjunction 
with the results from toxicological studies, provided ample and 
sufficient weight of evidence to conclude that exposure to DBPs in 
drinking water could result in increased cancer risk at levels 
encountered in some public water supplies. Other members of the 
Committee concluded that the cancer epidemiology studies on the 
consumption of chlorinated drinking water to date were insufficient to 
provide definitive information for the regulation. As a response, EPA 
agreed to pursue additional research to reduce the uncertainties 
associated with these data and to better characterize and project the 
potential human cancer risks associated with the exposure to 
chlorinated water. To implement this commitment, EPA sponsored an 
expert panel to review the state of cancer epidemiology research 
(USEPA, 1994b). As discussed in the 1997 NODA, EPA has implemented 
several of the panel's recommendations for short-and long-term research 
to improve the assessment of risks, using the results from cancer 
epidemiology studies.
    The 1994 proposed rule also presented the results of a meta-
analysis that pooled the relative risks from ten cancer epidemiology 
studies in which there was a presumed exposure to chlorinated water and 
its byproducts (Morris et al., 1992). A conclusion of this meta-
analysis was a calculated upper bound estimate of approximately 10,000 
cases of rectal and bladder cancer cases per year that could be 
associated with exposure to chlorinated water and its byproducts in the 
United States. The ten studies included in the meta-analysis had 
methodological issues and significant design differences. There was 
considerable debate among the members of the Negotiating Committee on 
the extent to which the results of this meta-analysis should be 
considered in developing benefit estimates associated with the proposed 
rule. Negotiators agreed that the range of possible risks attributed to 
chlorinated water should consider both toxicological data and 
epidemiological data, including the Morris et al. (1992) estimates. No 
consensus, however, could be reached on a single likely risk estimate.
    For purposes of estimating the potential benefits from the proposed 
rule, EPA used a range of estimated cancer cases that could be 
attributed to exposure to chlorinated waters of less than 1 cancer case 
per year up to 10,000 cases per year. The less than 1 cancer case per 
year was based on toxicology (the maximum likelihood cancer risk 
estimate calculated from animal assay data for THMs). The 10,000 cases 
per year was based on epidemiology (estimates from the Morris et al. 
(1992) meta-analysis).
1. Assessment of the Morris et al. (1992) Meta-Analysis
    Based on the recommendations from the 1994 expert panel on cancer 
epidemiology, EPA completed an assessment of the Morris et al. (1992) 
meta-analysis which comprises three reports: (1) A Report completed for 
EPA which evaluated the Morris et al. (1992) meta-analysis (Poole, 
1997); (2) EPA's assessment of the Poole report (USEPA, 1998f); and (3) 
a peer review of the Poole report and EPA's assessment of the Poole 
report (USEPA, 1998g). Each of these documents is briefly discussed 
below. The full reports together with Dr. Morris's comments on the 
Poole Review (Morris, 1997) can be found in the docket for this Notice.
    a. Poole Report. A report was prepared for EPA which made 
recommendations regarding whether the data used by Morris et al. (1992) 
should be aggregated into a single summary estimate of risk. The report 
also commented on the utility of the aggregated estimates for risk 
assessment purposes (Poole, 1997). This report was limited to the 
studies available to Morris et al. (1992) plus four additional studies 
that EPA requested to be included (Ijsselmuiden et al., 1992; McGeehin 
et al., 1993; Vena et al., 1993; and King and Marrett, 1996). Poole 
observed that there was considerable heterogeneity among the data and 
that there was evidence of publication bias within the body of 
literature. When there is significant heterogeneity among studies, 
aggregation of the results into a single summary estimate may not be 
appropriate. Publication bias refers to the situation where the 
literature search and inclusion criteria for studies used for the meta-
analysis indicate that the sample of studies used is not representative 
of all the research (published and unpublished) that has been done on a 
topic. In addition, Poole found that the aggregate estimates reported 
by Morris et al. (1992) were sensitive to small changes in the analysis 
(e.g., addition or deletion of a single study). Based on these 
observations, Poole recommended that the cancer epidemiology data 
considered in his evaluation should not be combined into a single 
summary estimate and that the data had limited utility for risk 
assessment purposes. Many of the reasons cited by Poole for why it was 
not appropriate to combine the studies into a single point estimate of 
risk were noted in the 1994 proposal (Farland and Gibb, 1993; Murphy, 
1993; and Craun, 1993).
    b. EPA's Evaluation of Poole Report. EPA reviewed the conclusions 
from the Poole report and generally concurred with Poole's 
recommendations (USEPA, 1998f). EPA concluded that Poole presented 
reasonable and supportable evidence to suggest that the work of Morris 
et al. (1992) should not be used for risk assessment purposes without 
further study and review because of the sensitivity of the results to 
analytical choices and to the addition or deletion of a single study. 
EPA agreed that the studies were highly heterogeneous, thus undermining 
the ability to combine the data into a single summary estimate of risk.
    c. Peer Review of Poole Report and EPA's Evaluation. The Poole 
report and EPA's evaluation were reviewed by five epidemiologic experts 
from academia, government, and industry (EPA, 1998g). Overall, these 
reviewers agreed that the Poole report was of high quality and that he 
had used defensible assumptions and techniques during his analysis. 
Most of the reviewers concluded that the report was correct in its 
assessment that these data should not be combined into a single summary 
estimate of risk.
2. New Cancer Epidemiology Studies
    Several cancer epidemiological studies examining the association 
between exposure to chlorinated surface water and cancer have been 
published subsequent to the 1994 proposed rule and the Morris et al. 
(1992) meta-analysis (McGeehin et al., 1993; Vena et al. 1993; King and 
Marrett, 1996; Doyle et al., 1997; Freedman et al., 1997; Cantor et al, 
1998; and Hildesheim et al., 1998). These studies, with the exception 
of Freedman et al. (1997), were described in the ``Summaries of New 
Health Effects Data'' (USEPA, 1997b) that was included in the docket 
for the 1997 NODA.
    In general, the new studies cited above are better designed than 
the studies published prior to the 1994 proposal. The newer studies 
generally include incidence cases of disease, interviews with the study 
subjects and better exposure assessments. Based on the entire cancer 
epidemiology database, bladder cancer studies provide

[[Page 15679]]

better evidence than other types of cancer for an association between 
exposure to chlorinated surface water and cancer. EPA believes the 
association between exposure to chlorinated surface water and colon and 
rectal cancer cannot be determined at this time because of the limited 
data available for these cancer sites (USEPA, 1998a).
3. Quantitative Risk Estimation for Cancers From Exposure to 
Chlorinated Water
    Under Executive Order 12866 (58 FR 51735, October 4, 1993), the EPA 
must conduct a regulatory impact analysis (RIA). In the 1994 proposal, 
EPA used the Morris et al. (1992) meta-analysis in the RIA to provide 
an upper-bound estimate of 10,000 possible cancer cases per year that 
could be attributed to exposure to chlorinated water and its associated 
byproducts. EPA also estimated that an upper bound of 1200-3300 of 
these cancer cases per year could be avoided if the requirements for 
the Stage 1 DBP rule were implemented (USEPA, 1994a). EPA acknowledged 
the uncertainty in these estimates, but believed they were the best 
that could be developed at the time.
    Based on the evaluations cited above, EPA does not believe it is 
appropriate to use the Morris et al. (1992) study as the basis for 
estimating the potential cancer cases that could be attributed to 
exposure to DBPs in chlorinated surface water. Instead, EPA is 
providing for comment an analysis based on a more traditional approach 
for estimating the potential cancer risks from exposure to DBPs in 
chlorinated surface water that does not rely on pooling or aggregating 
the epidemiologic data into a single summary estimate. Based on a 
narrower set of improved studies, this approach utilizes the population 
attributable risk (PAR) concept and presents a range of potential risks 
and not a single point estimate. As discussed below, there are a number 
of uncertainties associated with the use of this approach for 
estimating potential risks. Therefore, EPA requests comments on both 
the PAR methodology as well as on the assumptions upon which it is 
based.
    Epidemiologists use PAR to quantify the fraction of the disease 
burden in a population (e.g., cancer) that could be eliminated if the 
exposure was absent (e.g., DBPs in chlorinated water) (Rockhill, et 
al., 1998). PARs provide a perspective on the potential magnitude of 
risk associated with various exposures. The concept of PAR is known by 
many names (e.g, attributable fraction, attributable proportion, 
etiologic fraction). For this Notice, the term PAR will be used to 
avoid confusion. A range of PARs better captures the heterogeneity of 
the risk estimates than a single point estimate.
    In the PAR analysis of the cancer epidemiology data and the 
development of the range of potential cancer cases attributable to 
exposure to DBPs in chlorinated surface water, EPA recognizes that a 
causal relationship between chlorinated surface water and bladder 
cancer has not yet been demonstrated by epidemiology studies. However, 
several studies have suggested a weak association in various subgroups. 
EPA presents potential cancer case estimates as upper bounds of 
suggested risk as part of the Agency's analysis of potential costs and 
benefits associated with this rule. EPA focused its current evaluation 
on bladder cancer because the number of quality studies that are 
available for other cancer sites such as colon and rectal cancers are 
very limited.
    EPA estimated PARs for the best bladder cancer studies that 
provided enough information to calculate a PAR (USEPA, 1998a). In 
addition, EPA selected studies for inclusion in the quantitative 
analysis if they met all three of the following criteria: (1) The study 
was a population based case-control or cohort study conducted to 
evaluate the relationship between exposure to chlorinated drinking 
water and incidence cancer cases, based on personal interviews (no 
cohort studies were found that met all 3 criteria); (2) the study was 
of high quality and well designed (e.g., good sample size, high 
response rate, and adjusted for confounding factors); and (3) the study 
had adequate exposure assessments (e.g., residential histories, actual 
THM data). Based on the above selection criteria, five bladder cancer 
studies were selected for estimating PARs: Cantor et al., 1985; 
McGeehin et al. 1993; King and Marrett, 1996; Freedman et al., 1997; 
and Cantor et al., 1998. PARs were derived for two exposure categories: 
years of exposure to chlorinated surface water; and THM levels and 
years of chlorinated surface water exposure.
    The PARs from the five bladder cancer studies for the two exposure 
categories ranged from 2-17%. The uncertainties associated with these 
PAR estimates are large as expected, due to the common prevalence of 
both the disease (bladder cancer) and exposure (chlorinated drinking 
water). Based on 54,500 expected new bladder cancer cases in the U.S., 
as projected by NCI (1998) for 1997, the upper bound estimate of the 
number of potential bladder cancer cases per year potentially 
associated with exposure to DBPs in chlorinated surface water was 
estimated to be 1100-9300.
    EPA made several important assumptions when evaluating the 
application of the PAR range of estimated bladder cancer cases from 
these studies to the U.S. population. They include the following: (i) 
The study population selected for each of the cancer epidemiology 
studies are reflective of the entire U.S. population that develops 
bladder cancer; (ii) the percentage of bladder cancer cases exposed to 
DBPs in the reported studies are reflective of the bladder cancer cases 
exposed to DBPs in the U.S. population; (iii) the levels of DBP 
exposure in the bladder studies are reflective of the DBP exposure in 
the U.S. population; and (iv) the possible relationship between 
exposure to DBPs in chlorinated surface water and bladder cancer is 
causal.
    EPA believes that these assumptions would not be appropriate for 
estimating the potential upper bound cancer risk for the U.S. 
population based on a single study. However, the Agency believes that 
these assumptions are appropriate given the number of studies used in 
the PAR analysis and for gaining a perspective on the range of possible 
upper bound risks that can be used in establishing a framework for 
further cost-benefit analysis. In addition, EPA believes these 
assumptions are appropriate given the SDWA mandate that ``drinking 
water regulations be established if the contaminant may have an adverse 
effect on the health of persons'' (SDWA--Section 1412(b)(1)A). Because 
of this mandate, EPA believes that when the scientific data indicates 
there may be causality, such an analytical approach is appropriate. EPA 
believes the assumption of a potential causal relationship is supported 
by the weight-of-evidence from toxicology and epidemiology. Toxicology 
studies have shown several individual DBPs to be carcinogenic and 
mutagenic, while the epidemiology data have shown weak associations 
between several cancer sites and exposure to chlorinated surface water.
    EPA notes and requests comment on the following additional issues 
associated with basing an estimate of the potential bladder cancer 
cases that can be attributed to DBPs in chlorinated surface water from 
the five studies selected for this analysis. The results generally 
showed weak statistical significance and were not always consistent 
among the studies. For example, some reviewers believe that two studies 
showed statistically significant effects only for male smokers, while 
two other studies showed higher effects for non-smokers.

[[Page 15680]]

One study showed a significant association with exposure to chlorinated 
surface water but not chlorinated ground water, while another showed 
the opposite result. Furthermore, two studies which examined the 
effects of exposure to higher levels of THMs failed to find a 
significant association between level of THMs and cancer. The Agency 
notes that it is not necessary that statistical significance be shown 
in order to conduct a PAR analysis as was stated by peer-reviewers of 
this analysis.
4. Peer-Review of Quantitative Risk Estimates
    The quantitative cancer risks estimated from the five epidemiology 
studies derived through the calculation of individual PARs has 
undergone external peer review by three expert epidemiologists (USEPA, 
1998a). Two peer reviewers concurred with the decision to derive a PAR 
range. This approach was deemed more appropriate than the selection of 
a single study or aggregation of study results. One reviewer indicated 
significant reservations with this approach based not on the method, 
but the inconclusivity of the epidemiology database and stated that it 
was premature to perform a PAR analysis because it would suggest that 
the epidemiological information is more consistent and complete than it 
actually is. To better present the degree of variability, this reviewer 
suggested an alternative approach that involves a graphical 
presentation of the individual odds ratios and their corresponding 
confidence intervals. Two reviewers agreed that there is not enough 
information to present an estimate of the PAR for colon and rectal 
cancer.
    EPA understands the issues raised regarding the use of PARs and 
recognizes there may be controversy on using this approach with the 
available epidemiology data. However, as stated above, EPA believes the 
PAR approach is a useful tool for estimating the potential upper bound 
risk for use in developing the regulatory impact analysis. EPA agrees 
with two of the reviewers that there is not enough information to 
present an estimate of colon and rectal risk at this time using a PAR 
approach.
5. Summary of Key Observations
    The 1994 proposal included a meta-analysis of 10 cancer 
epidemiology studies that provided an estimate of the number of bladder 
and rectal cancer cases per year that could be attributed to 
consumption of chlorinated water and its associated byproducts (Morris 
et al., 1992). Based on the evaluations previously described, EPA does 
not believe it is appropriate to use the Morris et al. (1992) study as 
the basis for estimating the potential cancer cases that could be 
attributed to exposure to DBPs in chlorinated surface water. Instead, 
EPA has focused on a smaller set of higher quality studies and 
performed a PAR analysis to estimate the potential cancer risks from 
exposure to DBPs in chlorinated surface water that does not rely on 
pooling or aggregating the data into a single summary estimate, as was 
done by Morris et al. (1992). EPA focused the current evaluation on 
bladder cancer because there are more appropriate studies of higher 
quality available upon which to base this assessment than for other 
cancer sites. It was decided to present the potential number of cancer 
cases as a range instead of a single point estimate because this would 
better represent the uncertainties in the risk estimates. The number of 
potential bladder cancer cases per year that could be associated with 
exposure to DBPs in chlorinated surface water is estimated to be an 
upper bound range of 1100-9300 per year.
    In the PAR analysis of the cancer epidemiology data and the 
development of the range of potential cancer cases attributable to 
exposure to DBPs in chlorinated surface water, EPA presents the 
estimates as upper bounds of any suggested risk. As was debated during 
the 1992-1993 M/DBP Regulatory Negotiation process, EPA believes that 
there are insufficient data to conclusively demonstrate a causal 
association between exposure to DBPs in chlorinated surface water and 
cancer. EPA recognizes the uncertainties of basing quantitative 
estimates using the current health database on chlorinated surface 
waters and has identified a number of issues that must be considered in 
interpreting the results of this analysis. Nonetheless, the Agency 
believes that the overall weight-of-evidence from available 
epidemiologic and toxicologic studies on DBPs and chlorinated surface 
water continues to support a hazard concern and thus, a prudent public 
health protective approach for regulation.
6. Requests for Comments
    EPA is not considering any changes to the recommended regulatory 
approach contained in the 1994 proposal, and discussed further in the 
1997 NODA, based on the upper bound risk analysis issues discussed 
above. Nonetheless, EPA requests comments on the conclusions from the 
Poole report (Poole, 1997), EPA's assessment of the Poole report (EPA, 
1998f), the peer-review of the Poole report and EPA's assessment of the 
Poole report (EPA, 1998g); and Dr. Morris comments on the Poole review 
(Morris, 1997). EPA also requests comments on its quantitative analysis 
(PAR approach) to estimate the upper bound risks from exposure to DBPs 
in chlorinated surface water, the methodology for estimating the number 
of cancer cases per year that could be attributed to exposure to DBPs 
in chlorinated surface water, and any alternative approaches for 
estimating the upper bound estimates of risk. In particular, EPA 
requests comment on the extent to which the approach used in the PAR 
analysis addresses the concerns identified by Poole and others 
regarding the earlier Morris meta-analysis. EPA also requests comments 
on the peer review of the PAR analysis.

B. Epidemiologic Associations Between Exposure to DBPs in Chlorinated 
Water and Adverse Reproductive and Developmental Effects

    The 1994 proposed rule discussed several reproductive epidemiology 
studies. At the time of the proposal, it was concluded that there was 
no compelling evidence to indicate a reproductive and developmental 
hazard due to exposure to chlorinated water because the epidemiologic 
evidence was inadequate and the toxicological data were limited. In 
1993, an expert panel of scientists was convened by the International 
Life Sciences Institute to review the available human studies for 
developmental and reproductive outcomes and to provide research 
recommendations (USEPA/ILSI, 1993). The expert panel concluded that the 
epidemiologic results should be considered preliminary given that the 
research was at a very early stage (USEPA/ILSI, 1993; Reif et al., 
1996). The 1997 NODA and the ``Summaries of New Health Effects Data'' 
(USEPA, 1997b) presented several new studies (Savitz et al., 1995; 
Kanitz et al. 1996; and Bove et al., 1996) that had been published 
since the 1994 proposed rule and the 1993 ILSI panel review. Based on 
the new studies presented in the 1997 NODA, EPA stated that the results 
were inconclusive with regard to the association between exposure to 
chlorinated waters and adverse reproductive and developmental effects 
(62 FR 59395)

[[Page 15681]]

1. EPA Panel Report and Recommendations for Conducting Epidemiological 
Research on Possible Reproductive and Developmental Effects of Exposure 
to Disinfected Drinking Water
    EPA convened an expert panel in July 1997 to evaluate epidemiologic 
studies of adverse reproductive or developmental outcomes that may be 
associated with the consumption of disinfected drinking water published 
since the 1993 ILSI panel review. A report was prepared entitled ``EPA 
Panel Report and Recommendations for Conducting Epidemiological 
Research on Possible Reproductive and Developmental Effects of Exposure 
to Disinfected Drinking Water'' (USEPA, 1998h). The 1997 expert panel 
was also charged to develop an agenda for further epidemiological 
research. The 1997 panel concluded that the results of several studies 
suggest that an increased relative risk of certain adverse outcomes may 
be associated with the type of water source, disinfection practice, or 
THM levels. The panel emphasized, however, that most relative risks are 
moderate or small and were found in studies with limitations of their 
design or conduct. The small magnitude of the relative risk found may 
be due to one or more sources of bias, as well as to residual 
confounding (factors not identified and controlled). Additional 
research is needed to assess whether the observed associations can be 
confirmed. The panel considers a recent study by Waller et al. (1998), 
discussed below, to provide a strong basis for further research. This 
study was funded in part by EPA as an element of the research program 
agreed to as part of the 1992/1993 negotiated M/DBP rulemaking.
2. New Reproductive Epidemiology Studies
    Three new reproductive epidemiology studies have been published 
since the 1997 NODA. The first study (Klotz and Pyrch, 1998) examined 
the potential association between neural tube defects and certain 
drinking water contaminants, including some DBPs. In this case-control 
study, births with neural tube defects reported to New Jersey's Birth 
Defects Registry in 1993 and 1994 were matched against control births 
chosen randomly from across the State. Birth certificates were examined 
for all subjects, as was drinking water data corresponding to the 
mother's residence in early pregnancy. The authors reported elevated 
odds ratios (ORs), generally between 1.5 and 2.1, for the association 
of neural tube defects with TTHMs. However, the only statistically 
significant results were seen when the analysis was isolated to those 
subjects with the highest THM exposures (greater than 40 ppb) and 
limited to those subjects with neural tube defects in which there were 
no other malformations (odds ratio 2.1; 95% confidence interval 1.1-
4.0). Neither HAAs or haloacetonitriles (HANs) showed a clear 
relationship to neural tube defects but monitoring data on these DBPs 
were more limited than for THMs. Nitrates were not observed to be 
associated with neural tube defects. Certain chlorinated solvent 
contaminants were also studied but occurrence levels were too low to 
assess any relationship to neural tube defects. This study is available 
in the docket for this NODA. Although EPA has not completed its review 
of the study, the Agency is proceeding on the premise that this study 
will add to the weight-of-evidence concerning the potential adverse 
reproductive health effects from DBPs, but will not by itself provide 
sufficient evidence for further regulatory actions.
    Two studies looked at early term miscarriage risk factors. The 
first of these studies (Waller et al., 1998) examined the potential 
association between early term miscarriage and exposure to THMs. The 
second study (Swan et al., 1998) examined the potential association 
between early term miscarriage and tap water consumption. Both studies 
used the same group of pregnant women (5,144) living in three areas of 
California. They were recruited from the Santa Clara area, the Fontana 
area in southern California, or the Walnut Creek area. The women were 
all members of the Kaiser Permanente Medical Care Program and were 
offered a chance to participate in the study when they called to 
arrange their first prenatal visit. In the Waller et al. (1998) study, 
additional water quality information from the women's drinking water 
utilities were obtained so that THM levels could be determine. The Swan 
et al. (1998) study provided no quantitative measurements of THMs (or 
DBPs), and thus, provided no additional information on the risk from 
chlorination byproducts. Because of this, only the Waller et al. (1998) 
study is summarized below.
    In the Waller et al. (1998) study, utilities that served the women 
in this study were identified. Utilities' provided THM measurements 
taken during the time period participants were pregnant. The TTHM level 
in a participant's home tap water was estimated by averaging water 
distribution system TTHM measurements taken during a participants first 
three months of pregnancy. This ``first trimester TTHM level'' was 
combined with self reported tap water consumption to create a TTHM 
exposure level. Exposure levels of the individual THMs (e.g., 
chloroform, bromoform, etc.) were estimated in the same manner. Actual 
THM levels in the home tap water were not measured.
    Women with high TTHM exposure in home tap water (drinking five or 
more glasses per day of cold home tap water containing at least 75 ug 
per liter of TTHM) had an early term miscarriage rate of 15.7%, 
compared with a rate of 9.5% among women with low TTHM exposure 
(drinking less than 5 glasses per day of cold home tap water or 
drinking any amount of tap water containing less than 75 ug per liter 
of TTHM). An adjusted odds ratio for early term miscarriage of 1.8 (95% 
confidence interval 1.1-3.0) was determined.
    When the four individual trihalomethanes were studied, only high 
bromodichloromethane (BDCM) exposure, defined as drinking five or more 
glasses per day of cold home tap water containing 18 ug/L 
bromodichloromethane, was associated with early term miscarriage. An 
adjusted odds ratio for early term miscarriage of 3.0 (95% confidence 
interval 1.4-6.6) was determined.
3. Summary of Key Observations
    The Waller et al. (1998) study reports that consumption of tapwater 
containing high concentrations of THMs, particularly BDCM, is 
associated with an increased risk of early term miscarriage. EPA 
believes that while this study does not prove that exposure to THMs 
causes early term miscarriages, it does provide important new 
information that needs to be pursued and that the study adds to the 
weight-of-evidence which suggests that exposure to DBPs may have an 
adverse effect on humans.
    EPA has an epidemiology and toxicology research program that is 
examining the relationship between DBPs and adverse reproductive and 
developmental effects. In addition to conducting scientifically 
appropriate follow-up studies to see if the observed association in the 
Waller et al. (1998) study can be replicated elsewhere, EPA will be 
working with the California Department of Health Services to improve 
estimates of exposure to DBPs in the existing study population. A more 
complete DBP exposure data base is being developed by asking water 
utilities in the study area to provide additional information, 
including levels of other types of DBPs (e.g., haloacetic

[[Page 15682]]

acids). These efforts will help further assess the significance of the 
Waller et al. (1998) study, associated concerns, and how further 
follow-up work can best be implemented. EPA will collaborate with the 
Centers for Disease Control and Prevention (CDC) in a series of studies 
to evaluate if there is an association between exposure to DBPs in 
drinking water and birth defects. The Agency is also involved in a 
collaborative testing program with the National Toxicology Program 
(NTP) under which several individual DBPs have been selected for 
reproductive and developmental screening tests. Finally, EPA is 
conducting several toxicology studies on DBPs other endpoints of 
concern including examining the potential effects of BDCM on male 
reproductive endpoints. This information will be used in developing the 
Stage 2 DBP rule. In the meantime, the Agency plans to proceed with the 
1994 D/DBP proposal for tightening the control for DBPs.
4. Requests for Comments
    EPA is not considering any changes to the recommended regulatory 
approach contained in the 1994 proposal, and discussed further in the 
1997 NODA, based on the new reproductive epidemiology studies discussed 
above. Nonetheless, EPA requests comments on the findings from the 
Klotz, et al. (1998) and Waller et al. (1998) study and EPA's 
conclusions regarding the studies.

III. Significant New Toxicological Information for the Stage 1 
Disinfectants and Disinfection Byproducts

    The 1997 NODA reviewed new toxicological information that became 
available for several of the DBPs after the 1994 proposal (USEPA, 1997a 
and b). In that Notice, it was pointed out that several forthcoming 
reports were not available in time for consideration during the 1997 
FACA process. Reports now available include a two-generation 
reproductive rat study of sodium chlorite sponsored by the Chemical 
Manufacturer Association (CMA, 1996); an EPA two-year cancer rodent 
study of bromate (DeAngelo et al., 1998); and the International Life 
Sciences Institute (ILSI) expert panel report of chloroform and 
dichloroacetic acid (ILSI, 1997). These reports are discussed below, as 
well as EPA's analyses and conclusions based on this new information.

A. Chlorite and Chlorine Dioxide

    The 1994 proposal included an MCLG of 0.08 mg/L and an MCL of 1.0 
mg/L for chlorite. The proposed MCLG was based on an RfD of 3 mg/kg/d 
estimated from a lowest-observed-adverse-effect-level (LOAEL) for 
neurodevelopmental effects identified in a rat study by Mobley et al. 
(1990). This determination was based on a weight of evidence evaluation 
of all the available data at that time (USEPA, 1994a). An uncertainty 
factor of 1000 was used to account for inter- and intra-species 
differences in response to toxicity (a factor of 100) and a factor of 
10 for use of a LOAEL. The EPA proposed rule also included an MRDLG of 
0.3 mg/L and an MRDL of 0.8 mg/L for chlorine dioxide. The proposed 
MRDLG was based on a RfD of 3 mg/kg/d estimated from a no-observed-
adverse-effect-level (NOAEL) for developmental neurotoxicity identified 
from a rat study (Orme et al., 1985; see USEPA, 1994a). This 
determination was based on a weight of evidence evaluation of all the 
available data at that time (USEPA, 1994a). An uncertainty factor of 
300 was applied that was composed of a factor of 100 to account for 
inter- and intra-species differences in response to toxicity and a 
factor of 3 for lack of a two-generation reproductive study necessary 
to evaluate potential toxicity associated with lifetime exposure. To 
fill this important data gap, the Chemical Manufacturers Associations 
(CMA) agreed to conduct a two-generation reproductive study in rats. 
Sodium chlorite was used as the test compound. It should be noted that 
data on chlorite are relevant to assessing the risks of chlorine 
dioxide because chlorine dioxide rapidly disassociates to chlorite (and 
chloride) (USEPA, 1998b). Therefore, the new CMA two-generation 
reproductive chlorite study will be considered in assessing the risks 
for both chlorite and chlorine dioxide.
    Since the 1994 proposal, CMA has completed the two-generation 
reproductive rat study (CMA, 1996). EPA has reviewed the CMA study and 
has completed an external peer review of the study (EPA, 1997c). In 
addition, EPA has reassessed the noncancer health risk for chlorite and 
chlorine dioxide considering the new CMA study (USEPA, 1998b). This 
reassessment has been peer reviewed (USEPA, 1998b). Based on this 
reassessment, EPA is considering changing the proposed MCLG for 
chlorite from 0.08 mg/L to 0.8 mg/L based on the NOAEL identified from 
the new CMA study. Since data on chlorite are considered relevant to 
chlorine dioxide risks and the two generation reproduction data gap has 
been filled, EPA is also considering changing the proposed MRDLG for 
chlorine dioxide from 0.3 mg/L to 0.8 mg/L. The basis for these changes 
are discussed below.
1. 1997 CMA Two-Generation Reproduction Rat Study
    The CMA two-generation reproductive rat study was designed to 
evaluate the effects of chlorite (sodium salt) on reproduction and pre- 
and post-natal development when administered orally via drinking water 
for two successive generations (CMA, 1996). Developmental 
neurotoxicity, hematological, and clinical effects were also evaluated 
in this study.
    Sodium chlorite was administered at 0, 35, 70, and 300 ppm in 
drinking water to male and female Sprague Dawley rats (F0 
generation) for ten weeks prior to mating. Dosing continued during the 
mating period, pregnancy and lactation. Reproduction, fertility, 
clinical signs, and histopathology were evaluated in F0 and 
F1 (offspring from the first generation of mating) males and 
females. F1 and F2 (offspring from the second 
generation of mating) pups were evaluated for growth and development, 
clinical signs, and histopathology. In addition, F1 animals 
from each dose group were assessed for neurotoxicity (e.g., 
neurohistopathology, motor activity, learning ability and memory 
retention, functional observations, auditory startle response). Limited 
neurotoxicological evaluations were conducted on F2 pups.
    The CMA report concluded that there were no treatment related 
effects at any dose level for systemic, reproductive/developmental, and 
developmental neurological end points. The report indicates that there 
were small statistically significant decreases in the maximum response 
to auditory startle response in the F1 animals at the mid 
and high dose (70 and 300 ppm); this neurological effect was not 
considered to be toxicologically significant. A reduction in pup weight 
and decreased body weight gain through lactation in the F1 
and F2 animals and a decrease in body weight gain in the 
F2 males at 300 ppm were noted. Decreases in liver weight in 
F0 and F1 animals, as well as reductions in red 
blood cell indices in F1 animals at 300 ppm and 70 ppm were 
noted. Minor hematological effects were found in F1 females 
at 35 ppm. CMA concluded that the effects noted above were not 
clinically or toxicologically significant. A NOAEL of 300 ppm was 
identified in the CMA report for reproductive toxicity and for 
developmental neurotoxic effects, and a NOAEL of 70 ppm for 
hematological effects. EPA disagrees with the CMA conclusions regarding 
the NOAEL of 300 ppm for the reproductive and

[[Page 15683]]

developmental neurological effects for this study as discussed below.
2. External Peer Review of the CMA Study
    EPA has evaluated the CMA 2-generation reproductive study and 
concluded that the study design was consistent with EPA testing 
guidelines (USEPA, 1992). Additionally, an expert peer review of the 
CMA study was conducted and indicated that the study design and 
analyses were adequate (USEPA, 1997c). Although the study design was 
considered adequate and consistent with EPA guidelines, the peer review 
pointed out some limitations in the study (USEPA, 1997c). For example, 
developmental neurotoxicity evaluations were conducted after exposure 
ended at weaning. This is consistent with EPA testing guidelines and 
should potentially detect effects on the developing central nervous 
system. Nevertheless, the opportunity to detect neurological effects 
due to continuous or lifetime exposure may be reduced. The peer review 
generally questioned the CMA conclusions regarding the NOAELs for this 
study and indicated that the NOAEL should be lower than 300 ppm. The 
majority of peer reviews recommended that the NOAEL for reproductive/
developmental toxicity be reduced to 70 ppm given the treatment related 
effects found at 300 ppm, and that the NOAEL for neurotoxicity be 
reduced to 35 ppm based on significant changes in the maximum responses 
in startle amplitude and absolute brain weight at 70 and 300 ppm. The 
reviewers indicated that a NOAEL was not observed for hematological 
effects and noted that the CMA conclusion for selecting the 70 ppm 
NOAEL for the hematology variables needs to be explained further.
3. MCLG for Chlorite: EPA's Reassessment of the Noncancer Risk
    EPA has determined that the NOAEL for chlorite should be 35 ppm (3 
mg/kg/d chlorite ion, rounded) based on a weight of evidence approach. 
The data considered to support this NOAEL are summarized in USEPA 
(1998b) and included the CMA study as well as previous reports on 
developmental neurotoxicity (USEPA, 1998b). The NOAEL of 35 ppm (3 mg/
kg/d chlorite ion) is based on the following effects observed in the 
CMA study at 70 and 300 ppm chlorite: Decreases in absolute brain and 
liver weight, and lowered auditory startle amplitude. Decreases in pup 
weight were found at the 300 ppm and thus a NOAEL of 70 ppm for 
reproductive effects is considered appropriate (USEPA, 1998b). Although 
70 ppm appears to be the NOAEL for hemolytic effects, the NOAEL and 
LOAEL are difficult to discern for this endpoint given that minor 
changes were reported at 70 and 35 ppm. EPA considers the basis of the 
NOAELs to be consistent with EPA risk assessment guidelines (USEPA, 
1991, 1998i, 1996a). Furthermore, a NOAEL of 35 ppm is supported by 
effects (particularly neurodevelopmental effects) found in previously 
conducted studies of chlorite and chlorine dioxide (USEPA, 1998b).
    An RfD of 0.03 mg/kg/d is estimated using a NOAEL of 3 mg/kg/d and 
an uncertainty factor of 100 to account for inter- and intra-species 
differences. The revised MCLG for chlorite is calculated to be 0.8 mg/L 
by assuming an adult tap water consumption of 2 L per day for a 70 kg 
adult and using a relative source contribution of 80% (because most 
exposure to chlorite is likely to come from drinking water):
[GRAPHIC] [TIFF OMITTED] TP31MR98.024

Therefore, EPA is considering an increase in the proposed MCLG for 
chlorite from 0.08 mg/L to 0.8 mg/L. A more detailed discussion of this 
assessment is included in the docket for this Notice (USEPA, 1998b).
4. MRDLG for Chlorine Dioxide: EPA's Reassessment of the Noncancer Risk
    EPA believes that data on chlorite are relevant to assessing the 
risk of chlorine dioxide because chlorine dioxide rapidly disassociates 
to chlorite (and chloride) (USEPA, 1998b). Therefore, the findings from 
the 1997 CMA two-generation reproductive study on sodium chlorite 
should be considered in a weight of evidence approach for establishing 
the MRDLG for chlorine dioxide. Based on all the available data, 
including the CMA study, a dose of 3 mg/kg/d remains as the NOAEL for 
chlorine dioxide (USEPA, 1998b). The MRDLG for chlorine dioxide is 
increased 3 fold from the 1994 proposal since the CMA 1997 study was a 
two-generation reproduction study. Using a NOAEL of 3 mg/kg/d and 
applying an uncertainty factor of 100 to account for inter- and intra-
species differences in response to toxicity, the revised MRDLG for 
chlorine dioxide is calculated to be 0.8 mg/L. This MRDLG takes into 
account an adult tap water consumption of 2 L per day for a 70 kg adult 
and applies a relative source contribution of 80% (because most 
exposure to chlorine dioxide is likely to come from drinking water):
[GRAPHIC] [TIFF OMITTED] TP31MR98.025

EPA is considering revising the MRDLG for chlorine dioxide from 0.3 mg/
L to 0.8 mg/L. A more detailed discussion of this assessment can be 
found in the docket for this Notice (USEPA, 1998b).
5. External Peer Review of EPA's Reassessment
    Three external experts have reviewed the EPA reassessment for 
chlorite and chlorine dioxide (see USEPA, 1998b). Two of the three 
reviewers generally agreed with EPA conclusions regarding the 
identified NOAEL of 35 ppm for neurodevelopmental toxicity. The other 
reviewer indicated that the developmental neurological results from the 
CMA study were transient, too inconsistent, and equivocal to identify a 
NOAEL. EPA believes that although different responses were found for 
startle response (as indicated by measures of amplitude, latency, and 
habituation), this is not unexpected given that these measures examine 
different aspects of the nervous system, and thus can be differentially 
affected. Although no neuropathology was observed in the CMA study, 
neurofunctional (or neurochemical)

[[Page 15684]]

changes such as startle responses can indicate potential neurotoxicity 
without neuropathological effects. Furthermore, transient effects are 
considered an important indicator of neurotoxicity as indicated in EPA 
guidelines (USEPA, 1998i). EPA maintains that the NOAEL is 35 ppm (3 
mg/kg/d) from the CMA chlorite study based on neurodevelopmental 
effects as well as changes in brain and liver weight. This conclusion 
is supported by previous studies on chlorite and chlorine dioxide 
(USEPA, 1998b). Other comments raised by the peer reviewers concerning 
improved clarity and completeness of the assessment were considered by 
EPA in revising the assessment document on chlorite and chlorine 
dioxide.
6. Summary of Key Observations
    EPA continues to believe that chlorite and chlorine dioxide may 
have an adverse effect on the public health. EPA identified a NOAEL of 
35 ppm for chlorite based on neurodevelopmental effects from the 1997 
CMA two-generation reproductive study, which is supported by previous 
studies on chlorite and chlorine dioxide. In addition, EPA identified a 
NOAEL of 70 ppm for reproductive/developmental effects and hemolytic 
effects. EPA considers this study relevant to assessing the risk to 
chlorine dioxide. Based on the EPA reassessment, EPA is considering 
adjusting the MCLG for chlorite from 0.08 mg/L to 0.8 mg/L. Because 
data on chlorite are considered relevant to chlorine dioxide risks, EPA 
is considering adjusting the MRDLG for chlorine dioxide from 0.3 mg/L 
to 0.8 mg/L. The MRDL for chlorine dioxide would remain at 0.8 mg/L. 
The MCL for chlorite would remain at 1.0 mg/L because as noted in the 
1994 proposal, 1.0 mg/L for chlorite is the lowest level achievable by 
typical systems using chlorine dioxide and taking into consideration 
the monitoring requirements to determine compliance. In addition, given 
the margin of safety that is factored into the estimation of the MCLG, 
EPA believes that 1.0 mg/L will be protective of public health. It 
should be noted that the MCLG and MRDLG presented for chlorite and 
chlorine dioxide are considered to be protective of susceptible groups, 
including children given that the RfD is based on a NOAEL derived from 
developmental testing, which includes a two-generation reproductive 
study. A two-generation reproductive study evaluates the effects of 
chemicals on the entire developmental and reproductive life of the 
organism. Additionally, current methods for developing RfDs are 
designed to be protective for sensitive populations. In the case of 
chlorite and chlorine dioxide a factor of 10 was used to account for 
variability between the average human response and the response of more 
sensitive individuals.
7. Requests for Comments
    Based on the recent two-generation reproductive rat study for 
chlorite (CMA, 1996), EPA is considering revising the MCLG for chlorite 
from 0.08 mg/L to 0.8 mg/L and the MRDLG for chlorine dioxide from 0.3 
mg/L to 0.8 mg/L. EPA requests comments on these possible changes in 
the MCLGs and on EPA's assessment of the CMA report.

B. Trihalomethanes

    The 1994 proposed rule included an MCL for TTHM of 0.08 mg/L. MCLGs 
of zero for chloroform, BDCM and bromoform were based on sufficient 
evidence of carcinogenicity in animals. The MCLG of 0.06 mg/L for 
dibromochloromethane (DBCM) was based on observed liver toxicity from a 
subchronic study and limited animal evidence for carcinogenicity. As 
stated in the 1997 NODA, several new studies have been published on 
bromoform, BDCM, and chloroform since the 1994 proposal. The 1997 NODA 
concluded that the new studies on THMs contribute to the weight-of-
evidence conclusions reached in the 1994 proposed rule, and that the 
new studies are not anticipated to change the proposed MCLGs for BDCM, 
DBCM, and bromoform. Since the 1997 NODA, the EPA has evaluated the 
significance of an ILSI panel report on the cancer risk assessment for 
chloroform. EPA has conducted a reassessment of chloroform (USEPA, 
1998c), considering the ILSI report. The EPA reassessment of chloroform 
has been peer reviewed (USEPA, 1998c). Based on EPA's reassessment, the 
Agency is considering changing the proposed MCLG for chloroform from 
zero to 0.3 mg/L.
1. 1997 International Life Sciences Institute Expert Panel Conclusions 
for Chloroform
    In 1996, EPA co-sponsored an ILSI project in which an expert panel 
was convened and charged with the following objectives: (i) Review the 
available database relevant to the carcinogenicity of chloroform and 
DCA, excluding exposure and epidemiology data; (ii) consider how end 
points related to the mode of carcinogenic action can be applied in the 
hazard and dose-response assessment; (iii) use guidance provided by the 
1996 EPA Proposed Guidelines for Carcinogen Assessment to develop 
recommendations for appropriate approaches for risk assessment; and 
(iv) provide a critique of the risk assessment process and comment on 
issues encountered in applying the proposed EPA Guidelines (ILSI, 
1997). The panel was made up of 10 expert scientists from academia, 
industry, government, and the private sector. It should be emphasized 
that the ILSI report does not represent a risk assessment, per se, for 
chloroform (or DCA) but, rather, provides recommendations on how to 
proceed with a risk assessment for these two chemicals.
    To facilitate an understanding of the ILSI panel recommendations 
for the dose-response characterization of chloroform, the EPA 1996 
Proposed Guidelines for Carcinogen Risk Assessment must be briefly 
described. For a more detail discussion of these guidelines, refer to 
USEPA (1996b).
    The EPA 1996 Proposed Guidelines for Carcinogen Risk Assessment 
describes a two-step process to quantifying cancer risk (USEPA, 1996b). 
The first step involves modeling response data in the empirical range 
of observation to derive a point of departure. The second step is to 
extrapolate from this point of departure to lower levels that are 
within the range of human exposure. A standard point of departure was 
proposed as the lower 95% confidence limit on a dose associated with 
10% extra risk (LED10). Based on comments from the public 
and the EPA's Science Advisory Board, the central or maximum likelihood 
estimate (i.e., ED10) is also being considered as a point of 
departure. Once the point of departure is identified, a straight-line 
extrapolation to the origin (i.e., zero dose, zero extra risk) is 
conducted as the linear default approach. The linear default approach 
would be considered for chemicals in which the mode of carcinogenic 
action understanding is consistent with low dose linearity or as a 
science policy choice for those chemicals for which the mode of action 
is not understood.
    The EPA 1996 Proposed Guidelines for Carcinogen Risk Assessment are 
different from the 1986 guidelines approach that applied the linearized 
multi-stage model (LMS) to extrapolate low dose risk. The LMS approach 
under the 1986 guidelines was the only default for low dose 
extrapolation. Under the 1996 proposed guidelines both linear and 
nonlinear default approaches are available. The nonlinear approach 
applies a margin of exposure (MoE) analysis rather than estimating the 
probability of effects at low doses. In order to use the nonlinear 
default, the agent's mode of action in causing tumors must be 
reasonably understood.

[[Page 15685]]

The MoE analysis is used to compare the point of departure with the 
human exposure levels of interest (i.e., MoE = point of departure 
divided by the environmental exposure of interest). The key objective 
of the MoE analysis is to describe for the risk manager how rapidly 
responses may decline with dose. A shallow slope suggests less risk 
reduction at decreasing exposure than does a steep one. Information on 
factors such as the nature of response being used for the point of 
departure (i.e., tumor data or a more sensitive precursor response) and 
biopersistence of the agent are important considerations in the MoE 
analysis. A numerical default factor of no less than 10-fold each may 
be used to account for human variability and for interspecies 
differences in sensitivity when humans may be more sensitive than 
animals.
    The ILSI expert panel considered a wide range of information on 
chloroform including rodent tumor data, metabolism/toxicokinetic 
information, cytotoxicity, genotoxicity, and cell proliferation data. 
Based on its analysis of the data, the panel concluded that the weight 
of evidence for the mode of action understanding indicated that 
chloroform was not acting through a direct DNA reactive mechanism. The 
evidence suggested, instead, that exposure to chloroform resulted in 
recurrent or sustained toxicity as a consequence of oxidative 
generation of highly tissue reactive and toxic metabolites (i.e., 
phosgene and hydrochloric acid (HCl)), which in turn would lead to 
regenerative cell proliferation. Oxidative metabolism was considered by 
the panel to be the predominant pathway of metabolism for chloroform. 
This mode of action was considered to be the key influence of 
chloroform on the carcinogenic process. The ILSI report noted that the 
weight-of-evidence for the mode of action was stronger for the mouse 
kidney and liver responses and more limited, but still supportive, for 
the rat kidney tumor responses.
    The panel viewed chloroform as a likely carcinogen to humans above 
a certain dose range, but considered it unlikely to be carcinogenic 
below a certain dose range. The panel indicated that ``This mechanism 
is expected to involve a dose-response relationship which is nonlinear 
and probably exhibits an exposure threshold.'' The panel, therefore, 
recommended the nonlinear default or margin of exposure approach as the 
appropriate one for quantifying the cancer risk associated with 
exposure to chloroform.
2. MCLG for Chloroform: EPA's Reassessment of the Cancer Risk
    In the 1994 proposed rule, EPA classified chloroform under the 1986 
EPA Guidelines for Carcinogen Risk Assessment as a Group B2, probable 
human carcinogen. This classification was based on sufficient evidence 
of carcinogenicity in animals. Kidney tumor data in male Osborne-Mendel 
rats reported by Jorgenson et al. (1985) was used to estimate the 
carcinogenic risk. An MCLG of zero was proposed. Because the mode of 
carcinogenic action was not understood at that time, EPA used the 
linearized multistage model and derived an upper bound carcinogenicity 
potency factor for chloroform of 6  x  10-3 mg/kg/d. The 
lifetime cancer risk levels of 10-6, 10-5, and 
10-4 were determined to be associated with concentrations of 
chloroform in drinking water of 6, 60, and 600 g/L.
    Since the 1994 rule, several new studies have provided insight into 
the mode of carcinogenic action for chloroform. EPA has reassessed the 
cancer risk associated with chloroform exposure (USEPA, 1998c) by 
considering the new information, as well as the 1997 ILSI panel report. 
This reassessment used the principles of the 1996 EPA Proposed 
Guidelines for Carcinogen Risk Assessment (USEPA, 1996b), which are 
considered scientifically consistent with the Agency's 1986 guidelines 
(USEPA, 1986). Based on the current evidence for the mode of action by 
which chloroform may cause tumorgenesis, EPA has concluded that a 
nonlinear approach is more appropriate for extrapolating low dose 
cancer risk rather than the low dose linear approach used in the 1994 
proposed rule. Because tissue toxicity is key to chloroform's mode of 
action, EPA has also considered noncancer toxicities in determining the 
basis for the MCLG. After evaluating both cancer risk and noncancer 
toxicities as the basis for the MCLG, EPA concluded that the RfD for 
hepatoxicity should be used. Hepatotoxicity, thus, serves as the basis 
for the MCLG given that this is the primary effect of chloroform and 
the more sensitive endpoint. Therefore, EPA is considering changing the 
proposed MCLG for chloroform from zero to 0.3 mg/L based on the RfD for 
hepatoxicity. The basis for these conclusions are discussed below.
    a. Weight of the Evidence and Understanding of Mode of Carcinogenic 
Action. EPA has fully considered the 1997 ILSI report and the new 
science that has emerged on chloroform since the 1994 proposed rule. 
Based on this new information, EPA considers chloroform to be a likely 
human carcinogen by all routes of exposure (USEPA, 1998c). Chloroform's 
carcinogenic potential is indicated by animal tumor evidence (liver 
tumors in mice and renal tumors in both mice and rats) from inhalation 
and oral exposures, as well as metabolism, toxicity, mutagenicity and 
cellular proliferation data that contribute to an understanding of mode 
of carcinogenic action. Although the precise mechanism of chloroform 
carcinogenicity is not established, EPA agrees with the ILSI panel that 
a DNA reactive mutagenic mechanism is not likely to be the predominant 
influence of chloroform on the carcinogenic process. EPA believes that 
there is a reasonable scientific basis to support a mode of 
carcinogenic action involving cytotoxicity produced by the oxidative 
generation of highly reactive metabolites, phosgene and HCl, followed 
by regenerative cell proliferation as the predominant influence of 
chloroform on the carcinogenic process (USEPA, 1998c). EPA, therefore, 
agrees with the ILSI report that the chloroform dose-response should be 
considered nonlinear.
    A recent article by Melnick et al. (1998) was published after the 
1997 ISLI panel report and concludes that cytotoxicity and regenerative 
hyperplasia alone are not sufficient to explain the liver 
carcinogenesis in female B6C3F1 mice exposed to trihalomethanes, 
including chloroform. Although this article raises some interesting 
issues, EPA views the results for chloroform supportive of the role 
that toxicity and compensatory proliferation may play in chloroform 
carcinogenicity because statistically significant increases (p<0.05) in 
hepatoxicity and cell proliferation are found for chloroform in this 
study.
    b. Dose-Response Assessment. EPA has used several different 
approaches for estimating the MCLG for chloroform: the LED10 
for tumor response; the ED10 for tumor response; and the RfD 
for hepatoxicity. Each of these approaches are described below. EPA 
believes the RfD based on hepatotoxicity serves as the most appropriate 
basis for the MCLG for the reasons discussed below.
    EPA has presented the linear and nonlinear default approaches to 
estimating the cancer risk associated with drinking water exposure to 
chloroform (USEPA, 1998c). EPA considered the linear default approach 
because of remaining uncertainties associated with the understanding of 
chloroform's mode of carcinogenic action: for example, lack of data on

[[Page 15686]]

cytotoxicity and cell proliferation responses in Osborne-Mendel rats, 
lack of mutagenicity data on chloroform metabolites, and the lack of 
comparative metabolic data between humans and rodents. Although these 
data deficiencies raise some uncertainty about how chloroform may 
influence tumor development at low doses, EPA views the linear dose-
response extrapolation approach as overly conservative in estimating 
low-dose risk.
    EPA concludes that the nonlinear default or margin of exposure 
approach is the preferred approach to quantifying the cancer risk 
associated with chloroform exposure because the evidence is stronger 
for a nonlinear mode of carcinogenic action. The tumor kidney response 
data in Osborne-Mendel rats from Jorgenson et al. (1985) are used as 
the basis for the point of departure (i.e., LED10 and 
ED10) because a relevant route of human exposure (i.e., 
drinking water) and multiple doses of chloroform (i.e., 5 doses 
including zero) were used in this study (USEPA, 1998c). The animal data 
were adjusted to equivalent human doses using body weight raised to the 
\3/4\ power as the interspecies scaling factor, as proposed in the 1996 
EPA Proposed Guidelines for Carcinogen Risk Assessment. The 
ED10 and LED10 were estimated to be 37 and 23 mg/
kg/d, respectively.
    As part of the margin of exposure analysis, a 100 fold factor was 
applied to account for the variability and uncertainty associated with 
intra- and interspecies differences in the absence of data specific to 
chloroform. An additional factor of 10 was applied to account for the 
remaining uncertainties associated with the mode of carcinogenic action 
understanding and the nature of the tumor dose response relationship 
being relatively shallow. EPA believes 1000 fold represents an adequate 
margin of exposure that addresses inter- and intra-species differences 
and uncertainties in the database. Other factors considered in 
determining the adequacy of the margin of exposure include the size of 
the human population exposed, duration and magnitude of human exposure, 
and persistence in the environment. Taking these factors into 
consideration, a MoE of 1000 is still regarded as adequate. Although a 
large population is chronically exposed to chlorinated drinking water, 
chloroform is not biopersistent and humans are exposed to relatively 
low levels of chloroform in the drinking water (generally under 100 
g/L), which are below exposures needed to induce a cytotoxic 
response. Furthermore, EPA believes that a MoE of 1000 is protective of 
susceptible groups, including children. The mode of action 
understanding for chloroform's cytotoxic and carcinogenic effects 
involves a generalized mechanism of toxicity that is seen consistently 
across different species. Furthermore, the activity of the enzyme 
(i.e., CYP2E1) involved in generating metabolites key to chloroform's 
mode of action is not greater in children than in adults, and probably 
less (USEPA, 1998c). Therefore, the ED10 of 37 mg/kg-d and 
the LED10 of 23 mg/kg-d is divided by a MoE of 1000 giving 
dose estimates of 0.037 and 0.023 mg/kg/d for carcinogenicity, 
respectively. These estimates would translate into MCLGs of 1.0 mg/L 
and 0.6 mg/L, respectively.
    The underlying basis for chloroform's carcinogenic effects involve 
oxidative generation of reactive and toxic metabolites (phosgene and 
HCl) and thus are related to its noncancer toxicities (e.g., liver or 
kidney toxicities). It is important, therefore, to consider noncancer 
outcomes in the risk assessment (USEPA, 1998c). The electrophilic 
metabolite phosgene would react with macromolecules such as 
phosphotidyl inositols or tyrosine kinases which in turn could 
potentially lead to interference with signal transduction pathways 
(i.e., chemical messages controlling cell division), thus, leading to 
carcinogenesis. Likewise, it is also plausible that phosgene reacts 
with cellular phospholipids, peptides, and proteins resulting in 
generalized tissue injury. Glutathione, free cysteine, histidine, 
methionine, and tyrosine are all potential reactants for electrophilic 
agents. Hepatoxicity is the primary effect observed following 
chloroform exposure, and among tissues studied for chloroform-oxidative 
metabolism, the liver was found to be the most active (ILSI, 1997). In 
the 1994 proposed rule, data from a chronic oral study in dogs (Heywood 
et al., 1979) were used to derive the RfD of 0.01 mg/kg/d (USEPA, 
1994a). This RfD is based on a LOAEL for hepatotoxicity and application 
of an uncertainty factor of 1000 (100 was used to account for inter-and 
intra-species differences and a factor of 10 for use of a LOAEL). The 
MCLG is calculated to be 0.3 mg/L by assuming an adult tap water 
consumption of 2 L of tap water per day for a 70 kg adult, and by 
applying a relative source contribution of 80% (EPA assumes most 
exposure is likely to come from drinking water):
[GRAPHIC] [TIFF OMITTED] TP31MR98.026

    Therefore, 0.3 mg/L based on hepatoxicity in dogs (USEPA, 1994a) is 
being considered as the MCLG because liver toxicity is a more sensitive 
effect of chloroform than the induction of tumors. Even if low dose 
linearity is assumed, as it was in the 1994 proposed rule, a MCLG of 
0.3 mg/L would be equivalent to a 5 x 10-5 cancer risk 
level. EPA concludes that an MCLG based on protection against liver 
toxicity should be protective against carcinogenicity given that the 
putative mode of action understanding for chloroform involves 
cytotoxicity as a key event preceding tumor development. Therefore, the 
recommended MCLG for chloroform is 0.3 mg/L. The assessment that forms 
the basis for this conclusion can be found in the docket for this 
Notice (USEPA, 1998c).
3. External Peer Review of EPA's Reassessment
    Three external experts reviewed the EPA reassessment of chloroform 
(USEPA, 1998c). The peer review generally indicated that the nonlinear 
approach used for estimating the carcinogenic risk associated with 
exposure to chloroform was reasonable and appropriate and that the role 
of a direct DNA reactive mechanism unlikely. Other comments concerning 
improved clarity and completeness of the assessment were considered by 
EPA in revising the chloroform assessment document.
4. Summary of Key Observations
    Based on the available evidence, EPA concludes that a nonlinear 
approach should be considered for estimating the carcinogenic risk 
associated with lifetime exposure to chloroform via drinking water. It 
should be noted that the margin of exposure approach taken for 
chloroform carcinogenicity is consistent with conclusions reached in a 
recent report by the World Health

[[Page 15687]]

Organization for Chloroform (WHO, 1997). The 1994 proposed MCLG was 
zero for chloroform. EPA believes it should now be 0.3 mg/L given that 
hepatic injury is the primary effect following chloroform exposure, 
which is consistent with the mode of action understanding for 
chloroform. Thus, the RfD based on hepatoxicity is considered a 
reasonable basis for the chloroform MCLG. EPA believes that the RfD 
used for chloroform is protective of sensitive groups, including 
children. Current methods for developing RfDs are designed to be 
protective for sensitive populations. In the case of chloroform a 
factor of 10 was used to account for variability between the average 
human response and the response of more sensitive individuals. 
Furthermore, the mode of action understanding for chloroform does not 
indicate a uniquely sensitive subgroup or an increased sensitivity in 
children.
    EPA continues to conclude that exposure to chloroform may have an 
adverse effect on the public health. EPA also continues to believe the 
MCL of 0.080 mg/L for TTHMs is appropriate despite the increase in the 
MCLG for chloroform. EPA believes that the benefits of the 1994 
proposed MCL of 0.080 mg/L for TTHMs will result in reduced exposure to 
chlorinated DBPs in general, not solely THMs. EPA considers this a 
reasonable assumption at this time given the uncertainties existing in 
the current health and exposure databases for DBPs in general. 
Moreover, the MCLGs for BDCM and bromoform remain at zero and thus, a 
TTHM MCL of 0.080 mg/L is appropriate to assure that levels of these 
two THMs are kept as low as possible. In addition, the MCL for TTHMs is 
used as an indicator for the potential occurrence of other DBPs in high 
pH waters. The MCL of 0.080 mg/L for TTHMs to control DBPs in high pH 
waters (in conjunction with the MCL of 0.060 mg/L for HAA5 to control 
DBPs in lower pH waters) and enhanced coagulation treatment technique 
remains a reasonable approach at this time for controlling chlorinated 
DBPs in general and protecting the public health. There is ongoing 
research being sponsored by the EPA, NTP, and the American Water Works 
Research Foundation to better characterize the health risks associated 
with DBPs.
5. Requests for Comments
    Based on the information presented above, EPA is considering 
revising the MCLG for chloroform from zero to 0.30 mg/L. EPA requests 
comments on this possible change in the MCLG and on EPA's cancer 
assessment for chloroform based on the results from the ILSI report 
(1997) and new data.

C. Haloacetic Acids

    The 1994 proposed rule included an MCL of 0.060 mg/L for the 
haloacetic acids (five HAAs-monobromoacetic acid, dibromoacetic acid, 
monochloroacetic acid, dichloroacetic acid, and trichloroacetic acid). 
An MCLG of zero was proposed for dichloroacetic acid (DCA) based on 
sufficient evidence of carcinogenicity in animals, and an MCLG of 0.3 
mg/L for trichloroacetic acid (TCA) was based on developmental toxicity 
and possible carcinogenicity. As pointed out in the 1997 NODA, several 
toxicological studies have been identified for the haloacetic acids 
since the 1994 proposal (also see USEPA, 1997b).
    Since the 1997 NODA, the EPA has evaluated the significance of the 
1997 ILSI panel report on the cancer assessment for DCA. EPA has 
conducted a reassessment of DCA (USEPA, 1998e) using the principles of 
the EPA 1996 Guidelines for Carcinogen Risk Assessment (USEPA, 1996b), 
which are considered scientifically consistent with the Agency's 1986 
guidelines (USEPA, 1986). This reassessment has been peer reviewed 
(USEPA, 1998e). Based on the scope of the ILSI report, EPA's own 
assessment and comments from peer reviewers, the Agency believes that 
the MCLG for DCA should remain as proposed at zero. This conclusion is 
discussed in more detail below.
1. 1997 International Life Sciences Institute Expert Panel Conclusions 
for Dichloroacetic Acid (DCA)
    ILSI convened an expert panel in 1996 (ILSI, 1997) to explore the 
application of the USEPA's 1996 Proposed Guidelines for Carcinogen Risk 
Assessment (USEPA, 1996a) to the available data on the potential 
carcinogenicity of chloroform and dichloroacetic acid (as described 
under the chloroform section). The panel considered data on DCA which 
included chronic rodent bioassay data and information on mutagenicity, 
tissue toxicity, toxicokinetics, and other mode of action information.
    The ILSI panel concluded that the tumor dose-response (liver tumors 
only) observed in rats and mice was nonlinear (ILSI, 1997). The panel 
noted that the liver was the only tissue consistently examined for 
histopathology. It further concluded that all the experimental doses 
that produced tumors in mice also produce hepatoxicity (i.e., most 
doses used exceeded the maximally tolerated dose). Although the mode of 
carcinogenic action for DCA was unclear, the ISLI panel concluded that 
DCA does not directly interact with DNA. It speculated that the 
hepatocarcinogenicity was related to hepatotoxicity, cell 
proliferation, and inhibition of program cell death (apoptosis). The 
panel concluded that the potential human carcinogenicity of DCA 
``cannot be determined'' given the lack of adequate rodent bioassay 
data, as well as human data. This conclusion is in contrast to the 1994 
EPA proposal in which it was concluded that DCA was a Group 
B2 probable human carcinogen. In its current reevaluation of 
DCA carcinogenicity, EPA disagrees with the panel's conclusion that the 
human carcinogenic potential of DCA can not be determined. EPA's more 
recent assessment of DCA data includes published information not 
available at the time of the ILSI panel assessment. Based on the 
current weight of the evidence EPA concludes that DCA is a likely human 
carcinogen as it did in the 1994 proposed rule for the reasons 
discussed below.
2. MCLG for DCA: EPA's Reassessment of the Cancer Hazard
    In the 1994 proposed rule, DCA was classified as a Group B2, 
probable human carcinogen in accordance with the 1986 EPA Guidelines 
for Carcinogen Risk Assessment (USEPA, 1986). The DCA categorization 
was based primarily on findings of liver tumors in rats and mice, which 
was regarded as ``sufficient'' evidence in animals. No lifetime risk 
calculation was conducted at that time; EPA proposed an MCLG of zero 
(USEPA, 1994a).
    EPA has prepared a new hazard characterization regarding the 
potential carcinogenicity of DCA in humans (USEPA, 1998e). The 
objective of this report was to develop a weight-of-evidence 
characterization using the principles of the EPA's 1996 Proposed 
Guidelines for Carcinogen Risk Assessment (USEPA, 1996), as well as to 
consider the issues raised by the 1997 ILSI panel report. The EPA 
hazard characterization relies on information available in existing 
peer-reviewed source documents. Moreover, this hazard characterization 
considers published information not available to the ILSI panel (e.g., 
mutagenicity studies). This new characterization addresses issues 
important to interpretation of rodent cancer bioassay data, in 
particular, mechanistic information pertinent to the etiology of DCA-
induced rodent liver tumors and their relevance to humans.
    Based on the hepatocarcinogenic effects of DCA in both rats and 
mice in multiple studies, and mode of action

[[Page 15688]]

related effects (e.g., mutational spectra in oncogenes, elevated serum 
glucocorticoid levels, alterations in cell replication and death), EPA 
concludes that DCA should be considered as a ``likely'' cancer hazard 
to humans (USEPA, 1998e). This is similar to the 1994 view of a B2, 
probable human carcinogen, in the proposed rule.
    DCA concentrations as low as 0.5 g/L have been observed to cause a 
tumor incidence in mice of about 80% and in rats of about 20% in a 
lifetime bioassays, as well as inducing multiple tumors per animal 
(USEPA, 1998e). Higher doses of DCA are associated with up to 100% 
tumor incidence and as many as four tumors per animal in a number of 
studies. Time-to-tumor development in mice is relatively short and 
decreases with increased dose. The ILSI panel concluded that doses of 1 
g/L or greater in mice produced severe hepatotoxicity, and thus 
exceeded the MTD. They further indicated that there was marked 
hepatoxicity at 0.5 g/L of DCA, (albeit not as severe as the higher 
doses). EPA agrees that there was hepatoxicity at all the doses wherein 
there was a tumor response in mice. It should be noted that the MTD 
selected for the DeAngelo et al. (1991) mouse study was a dose that 
results in a 10% inhibition of body weight gain when compared to 
controls. This is within the limits designated in EPA guidelines 
(USEPA, 1998e). Furthermore, no hepatoxicity was seen in the rat 
studies, where DCA induced liver tumors of approximately 20% at the 
lowest dose, 0.5g/L (USEPA, 1998e). It appears that the ILSI report did 
not give full consideration to the rat tumor results as part of the 
overall weight-of-the-evidence for potential human carcinogenicity. EPA 
agrees with the ILSI panel, that the rodent assay data are not complete 
for DCA; for example, full histopathology is lacking for both sexes in 
two rodent species. This deficiency results in uncertainty concerning 
the potential of DCA to be tumorgenic at lower doses and at tissue 
sites other than liver. Nevertheless, the finding of increased tumor 
incidences as well as multiplicity at DCA exposure levels (0.5 g/L) in 
both rats and mice where minimal hepatotoxicity and no compensatory 
replication was seen supports the belief that observed tumors are 
related to chemical treatment.
    Although DCA has been found to be mutagenic and clastogenic, 
responses generally occur at relatively high exposure levels (USEPA, 
1998e). EPA acknowledges that a mutagenic mechanism may not be as 
important influence of DCA on the carcinogenic process at lower 
exposure levels as it might be at higher exposures. Evidence is still 
accumulating that suggests a mode of carcinogenic action for DCA 
through modification of cell signaling systems, with down-regulation of 
control mechanisms in normal cells giving a growth advantage to altered 
or initiated cells (USEPA, 1998e). The tumor findings in rodents and 
the mode of action information contributes to the weight-of-evidence 
concern for DCA (USEPA, 1998e; ILSI, 1997). EPA considers that a 
contribution of cytotoxicity and compensatory proliferation at high 
doses cannot be ruled out at this time; however, these effects were 
inconsistently observed in mice at lower exposure levels, and not at 
all in mice at 0.5 g/L, or in rats, at all exposure doses. Although the 
shape of the tumor dose responses are nonlinear, there is, however, an 
insufficient basis for understanding the possible mechanisms that might 
contribute to DCA tumorigenesis at low doses, as well as the shape of 
the dose response below the observable range of tumor responses.
    In summary, EPA considers the mode of action through which DCA 
induces liver tumors in both rats and mice to be unclear. As discussed 
above, EPA considers the overall weight of the evidence to support 
placing DCA in the ``likely'' group for human carcinogenicity 
potential. This hazard potential is indicated by tumor findings in mice 
and rats, and other mode of action data using the 1996 guideline 
weight-of-evidence process. The remaining uncertainties in the data 
base include incomplete bioassay studies for full histopathology and 
information on an understanding of DCA's mode of carcinogenic action. 
The likelihood of human hazard associated with low levels of DCA 
usually encountered in the environment or in drinking water is not 
understood. Although DCA tumor effects are associated with high doses 
used in the rodent bioassays, reasonable doubt exists that the mode of 
tumorgenesis is solely through mechanisms that are operative only at 
high doses. Therefore, as in the 1994 proposed rule, EPA believes that 
the MCLG for DCA should remain as zero to assure public health 
protection. NTP is implementing a new two year rodent bioassay that 
will include full histopathology at lower doses than those previously 
studied. Additionally, studies on the mode of carcinogenic action are 
being done by various investigators including the EPA health research 
laboratory.
3. External Peer Review of EPA's Reassessment
    Three external experts reviewed the EPA reassessment of DCA (USEPA, 
1998e). The review comments were generally favorable. There was a range 
of opinion on the issue of whether DCA should be considered a likely 
human cancer hazard. One reviewer agreed that the current data 
supported a human cancer concern for DCA, while another reviewer 
believed that it was premature to judge the human hazard potential. The 
third reviewer did not specifically agree or disagree with EPA's 
conclusion of ``likely'' human hazard. Other issues raised by the peer 
review concerned the dose response for DCA carcinogenicity. The peer 
review generally concluded on the one hand that the mode of action was 
incomplete to support a nonlinear approach, but on the other hand, the 
mutagenicity data did not support low dose linearity. One reviewer 
believed that the possibility of a low dose risk could not be 
dismissed. Other comments concerning improved clarity and completeness 
of the assessment were considered by EPA in revising the DCA assessment 
document.
4. Summary of Key Observations
    EPA continues to believe that exposure to DCA may have an adverse 
effect on the public health. Based on the above discussion, EPA 
considers DCA to be a ``likely'' cancer hazard to humans. This 
conclusion is similar to the conclusion reached in the 1994 proposed 
rule that DCA was a probable human carcinogen (i.e., Group 
B2 Carcinogen). EPA considers the DCA data inadequate for 
dose-response assessment, which was the view in the 1994 proposed rule. 
EPA, therefore, believes at this time that the MCLG should remain at 
zero to assure public health protection. The assessment that this 
conclusion is based on can be found in the docket for this Notice 
(USEPA, 1998e).
5. Requests for Comments
    Based on the information presented above, EPA is considering 
maintaining the MCLG of zero for DCA. EPA requests comments on 
maintaining the zero MCLG for DCA and on EPA's cancer assessment for 
DCA in light of conclusions from the ILSI report (1997) and new data.

D. Bromate

    The 1994 proposed rule included an MCL of 0.010 mg/L and an MCLG of 
zero for bromate. Since the 1994 proposed rule, EPA has completed and 
analyzed a new chronic cancer study in male rats and mice for bromate

[[Page 15689]]

(DeAngelo et al., 1998). EPA has reassessed the cancer risk associated 
with bromate exposure and had this reassessment peer reviewed (USEPA, 
1998d). Based on this reassessment, EPA believes that the MCLG for 
bromate should remain as zero.
1. 1998 EPA Rodent Cancer Bioassay
    In the cancer bioassay by DeAngelo et al. (1998), 78 male F344 rats 
were administered 0, 20, 100, 200, 400 mg/L potassium bromate 
(KBrO3) in the drinking water, and 78 male B6C3F1 mice were 
administered 0, 80, 400, 800 mg/L KBrO3. Exposure was 
continued through week 100. Although a slight increase in kidney tumors 
was observed in mice, there was not a dose-response trend. In rats, 
dose-dependent increases in tumors were found at several sites (kidney, 
testicular mesothelioma, and thyroid). This study confirms the findings 
of Kurokawa et al. (1986a and b) in which potassium bromate was found 
to be a multi-site carcinogen in rats.
2. MCLG for Bromate: EPA's Reassessment of the Cancer Risk
    In the 1994 proposal, EPA concluded that bromate was a probable 
human carcinogen (Group B2) under the 1986 EPA Guidelines for 
Carcinogen Risk Assessment weight of evidence classification approach. 
Combining the incidence of rat kidney tumors reported in two rodent 
studies by Kurokawa et al. (1986a), lifetime risks of 10-4 
10-5, and 10-6 were determined to be associated 
with bromate concentrations in water at 5, 0.5, and 0.05 ug/L, 
respectively.
    The new rodent cancer study by DeAngelo et al. (1998) contributes 
to the weight of the evidence for the potential human carcinogenicity 
of KBrO3 and confirms the study by Kurokawa et al. (1986a, 
b). Under the principles of the 1996 EPA Proposed Guidelines for 
Carcinogen Risk Assessment weight of evidence approach, bromate is 
considered to be a likely human carcinogen. This weight of evidence 
conclusion is based on sufficient experimental findings that include 
the following: Tumors at multiple sites in rats; tumor responses in 
both sexes; and evidence for mutagenicity including point mutations and 
chromosomal aberrations in vitro. It has been suggested that bromate 
causes DNA damage indirectly via lipid peroxidation, which generates 
oxygen radicals which in turn induce DNA damage. There is insufficient 
evidence, however, to establish lipid peroxidation and free radical 
production as key events responsible for the induction of the multiple 
tumor responses seen in the bromate rodent bioassays. The assumption of 
low dose linearity is considered to be a reasonable public health 
protective approach for extrapolating the potential risk for bromate 
because of limited data on its mode of action.
    Cancer risk estimates were derived from the DeAngelo et al. (1998) 
study by applying the one stage Weibull model for the low dose linear 
extrapolation (EPA, 1998d). The Weibull model, which is a time-to-tumor 
model, was considered to be the preferred approach to account for the 
reduction in animals at risk that may be due to the decreased survival 
observed in the high dose group toward the end of the study. However, 
mortality did not compromise the results of this study (USEPA, 1998d). 
The animal doses were adjusted to equivalent human doses using body 
weight raised to the \3/4\ power as the interspecies scaling factor as 
proposed in the 1996 EPA cancer guidelines (USEPA, 1996b). The 
incidence of kidney, thyroid, and mesotheliomas in rats were modeled 
separately and then the risk estimates were combined to represent the 
total potential risk to tumor induction. The upper bound cancer potency 
(q \1\*) for bromate ion is estimated to be 0.7 per mg/kg/d (USEPA, 
1998d). Assuming a daily water consumption of 2 liters for a 70 kg 
adult, lifetime risks of 10-4, 10-5 and 
10-6 are associated with bromate concentrations in water of 
5, 0.5 and 0.05 ug/L, respectively. This estimate of cancer risk from 
the DeAngelo et al. study is similar with the risk estimate derived 
from the Kurokawa et al. (1986a) study presented in the 1994 proposed 
rule. The cancer risk estimation presented for bromate is considered to 
be protective of susceptible groups, including exposures during 
childhood given that the low dose linear default approach was used as a 
public health conservative approach.
3. External Peer Review of the EPA's Reassessment
    Three external expert reviewers commented on the EPA assessment 
report for bromate (USEPA, 1998d). The reviewers generally agreed with 
the key conclusions in the document. The peer review indicated that it 
is a reasonable default to use the rat tumor data to estimate the 
potential human cancer risk. The peer review also indicated that the 
mode of carcinogenic action for bromate is not understood at this time, 
and thus it is reasonable to use a low dose linear extrapolation as a 
default. One reviewer indicated that it was not appropriate to combine 
tumor data from different sites unless it is shown that similar 
mechanisms are involved. EPA modeled the three tumor sites separately 
to derive the cancer potencies, and thus did not assume a similar mode 
of action. The slope factors from the different tumor response were 
combined in order to express the total potential tumor risk of bromate. 
Other comments raised by the peer reviewers concerning improved clarity 
and completeness of the assessment were considered by EPA in revising 
this document.
4. Summary of Key Observations
    EPA continues to believe that exposure to bromate may have an 
adverse effect on the public health. The DeAngelo et al. (1998) study 
confirms the tumor findings reported in the study by Kurokawa et al. 
(1986a) and contributes to the weight of the carcinogenicity evidence 
for bromate. EPA believes that the an MCL of 0.010 mg/L and an MCLG of 
zero should remain for bromate as proposed in 1994. The assessment that 
this conclusion is based on can be found in the docket for this Notice 
(USEPA, 1998d).
    5. Requests for Comments
    Based on the recent two-year cancer bioassay on bromate by DeAngelo 
et al. (1998), EPA is considering maintaining the MCLG of zero for 
bromate. EPA requests comments on maintaining the zero MCLG for bromate 
and on EPA's cancer assessment for bromate.

IV. Simultaneous Compliance Considerations: D/DBP Stage 1 Enhanced 
Coagulation Requirements and the Lead and Copper Rule

    EPA received comment on the November 3, 1997 Federal Register Stage 
1 D/DBP Notice of Data Availability that expressed concern regarding 
utilities' ability to comply with the Stage 1 D/DBP enhanced 
coagulation requirements and Lead and Copper Rule (LCR) requirements 
simultaneously. Commentors stated that enhanced coagulation will lower 
the pH and alkalinity of the water during treatment. They indicated 
concern that the lower pH and alkalinity levels may place utilities in 
noncompliance with the LCR by causing violations of optimal water 
quality control parameters and/or an exceedence of the lead or copper 
action levels. EPA is not aware of data that suggests that low pH and 
alkalinity levels cannot be adjusted upward following enhanced 
coagulation to meet LCR compliance requirements. However, as discussed 
below, the Agency solicits further comment and data on this issue.
    The LCR separates public water systems into three categories: large

[[Page 15690]]

(>50,000), medium (50,000 but >3,300) and small (<3,300). 
Small and medium systems that do not exceed the lead and copper action 
levels (90th percentile levels of 0.015 mg/L and 1.3 mg/L, 
respectively) during the required monitoring are deemed to have 
optimized corrosion control. These systems do not have to operate under 
optimal water quality control parameters. Optimal water quality control 
parameters consist of pH, alkalinity, calcium concentration, and 
phosphate and silicate corrosion inhibitors. They are designated by the 
State. Small and medium systems exceeding the action limits must 
operate under State specified optimal water quality parameters. Large 
systems must operate under optimal water quality parameters specified 
by the State unless the difference in lead levels between the source 
and tap water samples is less than the Practical Quantification Limit 
(PQL) of the prescribed method (0.005 mg/L).
    Maintenance of each optimal water quality control parameter 
mentioned above (except for calcium concentration) is directly related 
to meeting specified pH and alkalinity levels at the entry point to the 
distribution system and in tap samples to establish LCR compliance. In 
treatment trains that EPA is aware of, utilities have the technological 
capability to raise the pH (by adding caustic--NaOH, 
Ca(OH)2) and alkalinity (by adding Na2CO3 or 
NaHCO3) of the water following enhanced coagulation and 
before it enters the distribution system. Although certain utilities 
may need to add chemical feed points to provide chemical adjustment, pH 
and alkalinity can be maintained at the values used prior to the 
implementation of enhanced coagulation. Systems that operate with pH 
and alkalinity optimal water quality control parameters should be able 
to meet the State-prescribed values by providing pH and alkalinity 
adjustment prior to entry to the distribution system. Systems that 
operate without pH and alkalinity optimal water quality control 
parameters can raise the pH and alkalinity to the levels they were at 
before enhanced coagulation by providing chemical adjustment prior to 
distribution system entry.
    The goal of calcium carbonate stabilization is to precipitate a 
layer of CaCO3 scale on the pipe wall to protect it from 
corrosion. As the pH of a water decreases, the concentration of 
bicarbonate increases and the concentration of carbonate, which 
combines with calcium to form the desired CaCO3, decreases. 
At the lower pH used during enhanced coagulation, it will generally be 
more difficult to form calcium carbonate. However, post--coagulation pH 
adjustment will increase the pH and hence the concentration of 
carbonate available to form calcium carbonate scale. Systems that must 
meet a specific calcium concentration to remain in compliance with 
optimal water quality control parameters should not experience an 
increase in LCR violations due to the practice of enhanced coagulation 
provided the pH is adjusted prior to distribution system entry and the 
calcium level in the water prior to and after implementation of 
enhanced coagulation remains the same.
    EPA recognizes that the inorganic composition of the water may 
change slightly due to enhanced coagulation. For example, small amounts 
of anions and compounds that can affect corrosion rates (Cl-, 
SO4-2) may be removed or added to the water. The 
effect of these constituents is difficult to predict, but EPA believes 
they should be minimal for the great majority of systems due to the 
generally modest changes in the water's inorganic composition and 
because alkalinity and pH levels have a greater influence on corrosion 
rates. Increases in sulfate concentration due to increased alum 
addition during enhanced coagulation can actually lower the corrosion 
rates of lead pipe. EPA requests comment on whether changes in the 
inorganic matrix can be quantified to allow States to easily assess 
potential impacts to corrosion control.
    EPA requests comment on how lowering the pH and alkalinity during 
enhanced coagulation may cause LCR compliance problems, given that both 
pH and alkalinity levels can be adjusted to meet optimal water quality 
parameters prior to entry to the distribution system. EPA also requests 
comment on whether decreasing the pH and alkalinity during enhanced 
coagulation, and then increasing it prior to distribution system entry, 
may increase exceedences of lead and copper action levels.
    EPA is currently developing a simultaneous compliance guidance 
document working with stakeholders. The document will provide guidance 
to States and systems on maintaining compliance with other regulatory 
requirements (including the LCR) during and after the implementation of 
the Stage 1 D/DBP rule and the Interim Enhanced Surface Water Treatment 
Rule. EPA requests comment on what issues should be addressed in the 
guidance to mitigate concerns about simultaneous compliance with 
enhanced coagulation and LCR requirements. Further, the Agency requests 
comment on whether the proposed enhanced coagulation requirements and 
the existing LCR provisions that allow adjustment of corrosion control 
plans are flexible enough to address simultaneous compliance issues. Is 
additional regulatory language necessary to address this issue, or is 
guidance sufficient to mitigate potential compliance problems?

V. Compliance With Current Regulations

    EPA reaffirms its commitment to the current Safe Drinking Water Act 
regulations, including those related to microbial pathogen control and 
disinfection. Each public water system must continue to comply with the 
current regulations while new microbial and D/DBP rules are being 
developed.

VI. Conclusions

    This Notice summarizes new health information received and analyzed 
for DBPs since the November 3, 1997 NODA and requests comments on 
several issues related to the simultaneous compliance with the Stage 1 
D/DBP Rule and the Lead and Copper Rule. Based on this new information, 
EPA has developed several new documents. EPA is requesting comments on 
this new information and EPA's evaluation of the information included 
in the new documents. Based on an assessment of the new toxicology 
information, EPA believes the MCLs and MRDLs in the 1994 proposal, and 
confirmed in the 1997 FACA process, will not change. Based on the new 
information, EPA is considering increasing the proposed MCLG of zero 
for chloroform to 0.30 mg/L and the proposed MCLG for chlorite from 
0.080 mg/L to 0.80 mg/L. EPA is also considering increasing the MRDLG 
for chlorine dioxide from 0.3 mg/L to 0.8 mg/L.

VII. References

    1. Bove, F.J., et al. 1995. Public Drinking Water Contamination and 
Birth Outcomes. Amer. J. Epidemiol., 141(9), 850-862.
    2. Cantor KP, Hoover R, Hartge P, et al. 1985. Drinking water 
source and bladder cancer: a case-control study. In Jolley RL, Bull RJ, 
Davis WP, et al. (eds), Water chlorination: chemistry, environmental 
impact and health effects, vol. 5. Lewis Publishers, Inc., Chelsea, MI 
pp 145-152
    3. Cantor KP, Hoover R, Hartge P. et al. 1987. Bladder cancer, 
drinking water

[[Page 15691]]

source and tap water consumption: a case control study. JNCI; 79:1269-
79.
    4. Cantor KP, Lunch CF, Hildesheim M, Dosemeci M, Lubin J, Alavanja 
M, Craun GF. 1998. Drinking water source and chlorination byproducts. 
I. Risk of bladder cancer. Epidemiology; 9:21-28.
    5. CMA. 1997. Sodium Chlorite: Drinking Water Rat Two-Generation 
Reproductive Toxicity Study. Chemical Manufacturers Association. 
Quintiles Report Ref. CMA/17/96.
    6. Craun, G.F. 1993. Epidemiology studies of water disinfection and 
disinfection byproducts. In: Proceedings: Safety of Water Disinfection: 
Balancing Chemical and Microbial Risk. pp. 277-303, International Life 
Sciences Institute Press, Washington, D.C.
    7. Deangelo, A.B., Daniel, F.B, Stober, J.A., and Olson, G.R. 1991. 
The Carcinogenicity of Dichloroacetic Acid in the Male B6C3F1 mouse. 
Fundam. Appli. Toxicol. 16:337-347.
    8. DeAngelo AB, George MH, Kilburn SR, Moore TM, Wolf DC. 1998. 
Carcinogenicity of Potassium Bromate Administered in the Drinking Water 
to Make B6C3F1 Mice and F344/N Rats, Toxicologic Pathology vol. 26, No. 
4 (in press).
    9. Doyle TJ, Sheng W, Cerhan JR, Hong CP, Sellers TA, Kushi, LH, 
Folsom AR. 1997. The association of drinking water source and 
chlorination by-products with cancer incidence among postmenopausal 
women in Iowa: a prospective cohort study. American Journal of Public 
Health. 87:7.
    10. Farland, WH and HJ Gibb. 1993. U.S. perspective on balancing 
chemical and microbial risks of disinfection. In: Proceedings: Safety 
of Water Disinfection: Balancing Chemical and Microbial Risk. pp. 3-10, 
International Life Sciences Institute Press, Washington, D.C.
    11. Freedman M, Cantor KP, Lee NL, Chen LS, Lei HH, Ruhl CE, and 
Wang SS. 1997. Bladder cancer and drinking water: a population-based 
case-control study in Washington County, Maryland (United States). 
Cancer Causes and Control. 8, pp 738-744.
    12. Heywood R, et al. 1979. Safety Evaluation of Toothpaste 
Containing Chloroform. III. Long-Term Study in Beagle Dogs. J. Environ. 
Pathol. Toxicolo. 2:835-851.
    13. Hildesheim ME, Cantor KP, Lynch CF, Dosemeci M, Lubin J, 
Alavanja M, and Craun GF. 1998. Drinking water source and chlorination 
byproducts: Risk of colon and rectal cancers. Epidemiology. 9:1, pp: 
29-35.
    14. Ijsselmuiden CB, et al. 1992. Cancer of the Pancreas and 
Drinking Water: A Population-Based Case-Control Study in Washington 
County, Maryland. Am. J. Epidemiol. 136:836-842.
    15. ILSI. 1997. An Evaluation of EPA's Proposed Guidelines for 
Carcinogen Risk Assessment Using Chloroform and Dichloroacetate as Case 
Studies: Report of an Expert Panel. International Life Sciences 
Institute, Health and Environmental Sciences Institute November, 1997.
    16. Jorgenson, TA, EF Meier henry, CJ Rushbrrok, RJ Bull, and M. 
Robinson. 1985. Carcinogenicity of chloroform in drinking water to male 
Osborne-Mendal rats and female B6C3F1 mice. Fundam. Appl. Toxicol. 
5:760-769.
    17. Kanitz, S. et al. 1996. Association Between Drinking Water 
Disinfection and Somatic Parameters at Birth. Environ. Health 
Perspectives, 104(5), 516-520.
    18. King, W. D. and L. D. Marrett. 1996. Case-Control Study of 
Water Source and Bladder Cancer. Cancer Causes and Control, 7:596-604.
    19. Klotz, JB and Pyrch, LA. 1998. A Case-Control Study of Neural 
Tube Defects and Drinking Water Contaminants. New Jersey Department of 
Health and Senior Services. Sponsored by Agency for Toxic Substances 
and Disease Registry. January 1998.
    20. Kurokawa et al. 1986a Long-term in vivo carcinogenicity tests 
of potassium bromate, sodium hypochlorite, and sodium chlorite 
conducted in Japan. Environ Health Perspect 69:221-235.
    21. Kurokawa et al. 1986b. Dose response studies on the 
carcinogenicity of potassium bromate in F344 rats after long-term oral 
administration. J Natl Cancer Inst 77:977-982.
    22. Melnick, R., M. Kohn, J.K. Dunnick, and J.R. Leininger. 1998. 
Regenerative Hyperplasia Is Not Required for Liver Tumor Induction in 
Female B6C3F1 Mice Exposed to Trihalomethanes. Tox. And Applied Pharm. 
148: 137-147.
    23. McGeehin, M. A. et al. 1993. Case-Control Study of Bladder 
Cancer and Water Disinfection Methods in Colorado. Am. J. Epidemiology, 
138:492-501.
    24. Mobley, S.A, D.H. Taylor, R.D. Laurie, and R.J. Pfohl. 1990. 
Chlorine dioxide depresses T3 uptake and delays development of 
locomotor activity in young rats. In: Water Chlorination: Chemistry, 
Environmental Impact and Health Effects. Vol 6. Lolley, Condie, 
Johnson, Katz, Mattice and Jacobs, ed. Lewis Publ., Inc. Chelsea MI., 
pp. 347-360.
    25. Morris, R.D. et al. 1992. Chlorination, Chlorination By-
products, and Cancer: A Meta-Analyis. American Journal of Public 
Health, 82(7): 955-963.
    26. Morris, RD. 1997. Letter from Dr. RD Morris to Patricia Murphy 
on response to Poole Critique. December 11, 1997.
    27. Murphy, PA. 1993. Quantifying chemical risk form 
epidemiological studies: application to the disinfectant byproduct 
issues. In: Proceedings: Safety of Water Disinfection: Balancing 
Chemical and Microbial Risk. pp. 373-389, International Life Sciences 
Institute Press, Washington, D.C.
    28. NCI. 1998. Cancer Facts, National Cancer Institute, National 
Institutes of Health. http://www.meb.uni-bonn.de/cancer net/600314.html
    29. Orme, J. D.H. Taylor, R.D. Laurie, and R.J. Bull. 1985. Effects 
of Chlorine Dioxide on Thyroid Function in Neonatal Rats. J. Tox. and 
Environ. Health. 15:315-322.
    30. Poole, C. 1997. Analytical Meta-Analysis of Epidemiological 
Studies of Chlorinated Drinking Water and Cancer: Quantitative Review 
and Reanalysis of the Work Published by Morris et al., Am J Public 
Health 1992:82:955-963. National Center for Environmental Assessment, 
Office of Research and Development, September 30, 1997.
    31. Reif, J. S. et al. 1996. Reproductive and Developmental Effects 
of Disinfection By-products in Drinking Water. Environmental Health 
Prospectives. 104(10):1056-1061.
    32. Rockhill, B, B. Newman, and C. Weinberg. 1998. Use and Misuse 
of Population Attributable Fraction. Am. J. Public Health. 88(1):15-19.
    33. Savitz, D. A., Andrews, K. W. and L. M. Pastore. 1995. Drinking 
Water and Preganancy Outcome in Central North Carolina: Source, Amount, 
and Trihalomethane levels. Environ. Health Perspectives. 103(6), 592-
596.
    34. Swan SH, Waller K, Hopkins B, Windham G, Fenster L, Schaefer C, 
Neutra R., 1998. A prospective study of spontaneous abortion: Relation 
to amount and source of drinking water consumed in early pregnancy, 
Epidemiology 9(2):126-133.
    35. U.S. EPA. 1979. National Interim Primary Drinking Water 
Regulations; Control of Trihalomethanes in Drinking Water. Vol. 44, No. 
231. November 29, 1979. Pp. 68624-68707.
    36. U.S. EPA. 1986. Guidelines for carcinogen risk assessment, FR 
51(185):33992-34003.
    37. U.S. EPA. 1991. Guidelines for developmental toxicity risk 
assessment (Notice), FR 56(234):63798-63826.
    38. U.S. EPA. 1992. Guidelines for reproductive testing. CFR 
798.4700. July 1, 1992.

[[Page 15692]]

    39. U.S. EPA/ILSI. 1993. A Review of Evidence on Reproductive and 
Developmental Effects of Disinfection By-Products in Drinking Water. 
Washington: U.S. Environmental Protection Agency and International Life 
Sciences Institute.
    40. U.S. EPA. 1994a. National Primary Drinking Water Regulations; 
Disinfectants and Disinfection Byproducts; Proposed Rule. FR, 
59:145:38668. (July 29, 1994).
    41. U.S. EPA. 1994b. Workshop Report and Recommendations for 
Conducting Epidemiologic Research on Cancer and Exposure to Chlorinated 
Drinking Water. U.S. EPA, July 19-21, 1994.
    42. U.S. EPA. 1994c. U.S. Environmental Protection Agency. 
Regulatory Impact Analysis of Proposed Disinfectant/Disinfection By-
Products Regulations. Washington, D.C.
    43. U.S. EPA. 1996a. Reproductive toxicity risk assessment 
guidelines, FR 61(212):56274-56322.
    44. U.S. EPA. 1996b. Proposed guidelines for carcinogen risk 
assessment, FR 61(79):17960-18011.
    45. U.S. EPA. 1997a. National Primary Drinking Water Regulations; 
Disinfectants and Disinfection Byproducts; Notice of Data Availability; 
Proposed Rule. Fed. Reg., 62 (No. 212):59388-59484. (November 3, 1997).
    46. U.S. EPA. 1997b. Summaries of New Health Effects Data. Office 
of Science and Technology, Office of Water. October 1997.
    47. U.S. EPA. 1997c. External Peer Review of CMA Study -2- 
Generation, EPA Contract No. 68-C7-0002, Work Assignment B-14, The 
Cadmus Group, Inc., October 9, 1997.
    48. U.S. EPA. 1998a. Quantification of Cancer Risk from Exposure to 
Chlorinated Water. Office of Science and Technology, Office of Water. 
March 13, 1998.
    49. U.S. EPA. 1998b. Health Risk Assessment/Characterization of the 
Drinking Water Disinfection Byproduct Chlorine Dioxide and the 
Degradation Byproduct Chlorite. Office of Science and Technology, 
Office of Water. March 13, 1998.
    50. U.S. EPA. 1998c. Health Risk Assessment/Characterization of the 
Drinking Water Disinfection Byproduct Chloroform. Office of Science and 
Technology, Office of Water. March 13, 1998.
    51. U.S. EPA. 1998d. Health Risk Assessment/Characterization of the 
Drinking Water Disinfection Byproduct Bromate. Office of Science and 
Technology, Office of Water. March 13, 1998.
    52. U.S. EPA. 1998e. Dichloroacetic acid: Carcinogenicity 
Identification Characterization Summary. National Center for 
Environmental Assessment--Washington Office. Office of Research and 
Development. March 1998.
    53. U.S. EPA. 1998f. NCEA Position Paper Regarding Risk Assessment 
Use of the Results from the Published Study: Morris et al. Am J Public 
Health 1992;82:955-963. National Center for Environmental Assessment, 
Office of Research and Development, October 7, 1997.
    54. U.S. EPA. 1998g. Synthesis of the Peer-Review of Meta-analysis 
of Epidemiologic Data on Risks of Cancer from Chlorinated Drinking 
Water. National Center for Environmental Assessment, Office of Research 
and Development, February 16, 1998.
    55. U.S. EPA. 1998h. EPA Panel Report and Recommendation for 
Conducting Epidemiological Research on Possible Reproductive and 
Developmental Effects of Exposure to Disinfected Drinking Water. Office 
of Research and Development.
    56. U.S. EPA. 1998i. Final guidelines for neurotoxicity risk 
assessment.
    57. Vena JE, Graham S, Freudenheim JO, Marshall J, Sielezny M, 
Swanson M, Sufrin G. 1993. Drinking water, fluid intake, and bladder 
cancer in western New York. Archives of Environmental Health. 48:(3)
    58. Waller K, Swan SH, DeLorenze G, Hopkins B., 1998. 
Trihalomethanes in drinking water and spontaneous abortion. 
Epidemiology. 9(2):134-140.
    59. WHO. 1997. Rolling Revision of WHO Guidelines for Drinking-
Water Quality; Report of Working Group Meeting on Chemical Substances 
for the Updating of WHO Guidelines for Drinking-Water Quality. Geneva, 
Switzerland, 22-26 April 1997.
    National Primary Drinking Water Regulations: Disinfectants and 
Disinfection Byproducts Notice of Data Availability page 86 of 86.

    Dated: March 24, 1998.
Robert Perciasepe,
Assistant Administrator for Office of Water.
[FR Doc. 98-8215 Filed 3-30-98; 8:45 am]
BILLING CODE 6560-50-U