[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]]
_______________________________________________________________________
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.
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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 owdocket@epamail.epa.gov.
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
[[Page 15677]]
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="">10
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,="">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
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of Science and Technology, Office of Water. October 1997.
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51. U.S. EPA. 1998d. Health Risk Assessment/Characterization of the
Drinking Water Disinfection Byproduct Bromate. Office of Science and
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52. U.S. EPA. 1998e. Dichloroacetic acid: Carcinogenicity
Identification Characterization Summary. National Center for
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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.
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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
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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
