EPA
United States
Environmental Protection
Agency
Six-Year Review
Chemical
Contaminants
Health Effects
Technical Support
Document
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Office of Water
Office of Science and Technology
EPA 822-R-02-001
February 2002
Printed on Recycled Paper
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EPA 822-R-02-001
Six-Year Review
Chemical Contaminants
Health Effects
Technical Support Document
February 2002
United States Environmental Protection Agency
Office of Water
Office of Science and Technology
Health and Ecological Criteria Division
1200 Pennsylvania Avenue, NW (4304T)
Washington, DC 20460
This report is issued in support of the preliminary revise/not revise decisions for the Six-Year
Review Notice of Intent. It is intended for public comment and does not represent final Agency
policy. EPA expects to issue a final version of this report with the publication of the final notice
in 2002, reflecting corrections due to public comment on the preliminary notice and the
supporting documents.
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CONTENTS
Abbreviations :...... ii
1. Introduction 1
2. Maximum contaminant level goal 1
2.1. Reference dose 1
2.2. Assessment of carcinogenicity : 2
3. Identifying candidates for possible regulatory revision 3
4. Nomination of chemicals for new risk.assessment . 5
4.1. Priority chemicals of potential reproductive/developmental concern . . . .; 5
4.2. Other nominations for new risk assessment '. 7
5. Summary 9
6. References ....;..... ...... 10
Tables
Table 1. Cancer classification systems used by EPA 13
Table 2. Chemicals considered under the first six-year review cycle 14
Table 3. Assessment by IRIS, OPP, ATSDR, and NAS of chemicals considered under
the first six-year review cycle 21
Table 4. Evaluation of the literature search for reproductive and developmental toxicity .... 25
Table 5. Overall review of chemicals 27
Six-Year Review Draft Health Effects Technical Support DocumentFebruary 2002
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Abbreviations
ATSDR Agency for Toxic Substances and Disease Registry
BMD Benchmark dose
DEHA Di(2-ethylhexyl)adipate
EC European Commission
EPA U.S. Environmental Protection Agency
FQPA Food Quality Protection Act
GI Gastrointestinal
IARC International Agency for Research on Cancer
IRIS Integrated Risk Information System
LOAEL Lowest-observed-adverse-effect level
MCL Maximum contaminant level
MCLG Maximum contaminant level goal
MF Modifying factor
MFL Million fibers per liter
MRL Minimal risk level
NA Not available
NAS National Academy of Sciences
NDWAC National Drinking Water Advisory Council
NIEHS National Institute of Environmental Health Sciences
NOAEL No-observed-adverse-effect level
NPDWR National primary drinking water regulation
NTP National Toxicology Program
OPP Office of Pesticide Programs
OST Office of Science and Technology
OW Office of Water
RfD Reference dose
RSC Relative source contribution
SDWA Safe Drinking Water Act
TT Treatment technology
UF Uncertainly factor
UL Tolerable upper intake level
WHO World Health Organization
11
Six-Year Review Draft Health Effects Technical Support Document February 2002
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1. INTRODUCTION
EPA has developed a. Protocol for the Review of Existing National Primary Drinking Water
Regulations (US EPA 2002a) based on recommendations of the National Drinking Water
Advisory Council (NDWAC 2000), through consultations with stakeholders representing a wide
variety of interest groups, and internal Agency deliberations. The Protocol outlines the approach
to be used to review and identify national primary drinking water regulations (NPDWRs) that
warrant revision, to maintain, or provide for greater, public health protection. The key elements
of the review process are health effects, analytical and treatment technology, other regulatory
revisions (e.g., monitoring and reporting requirements), occurrence and exposure analysis, and,
as appropriate, economic considerations.
The purpose of the health effects component of the review process is to identify, within the
limitations of the Agency's available resources, new health risk assessments that indicate
possible change to the maximum contaminant level goal (MCLG) and, perhaps, to the maximum
contaminant level (MCL).
A total of 68 regulated chemical contaminants are being considered during this first 6-year
review cycle. These are inorganic and organic contaminants regulated prior to the Safe Drinking
Water Act amendments of 1996, except arsenic, radionuclides, disinfectant residuals, and
disinfection by-products, which have undergone recent revision.
2. MAXIMUM CONTAMINANT LEVEL GOAL
Because the identification of contaminants for potential revision based on health effects is
dependent on whether or not the MCLG could change, a brief explanation of the derivation of the
MCLG is warranted. The MCLG is the maximum level of a contaminant in drinking water at
which no known or anticipated adverse health effects occur, allowing for an adequate margin of
safety. MCLGs are nonenforceable health goals. EPA establishes the MCL based on the MCLG.
The MCL is the maximum permissible level of a contaminant in water that is delivered to any
user of a public water system. Prior to the 1996 Amendments to the SDWA, the MCL was set as
close to the MCLG as was feasible. The 1996 Amendments to the SDWA permit consideration
of costs and benefits in establishing an MCL. MCLs are enforceable standards.
2.1. Reference Dose
For chemicals exhibiting a threshold for toxic effects, EPA establishes the MCLG on the
basis of an oral reference dose (RfD). A change in the RfD could lead to a change in the MCLG
and thus in the MCL. The RfD is an estimate (with uncertainty spanning perhaps an order of
magnitude) of a daily oral exposure to the human population (including sensitive subgroups) that
is likely to be without an appreciable risk of deleterious noncancer effects during a lifetime. The
RfD is derived as follows:
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RfD (mg/kg/day) = NOAEL or LOAEL or BMP
UF x MF
where:
NOAEL = no-observed-adverse-effect level (mg/kg/day)
LOAEL = lowest-observed-adverse-effect level (mg/kg/day)
BMD = benchmark dose (mg/kg/day)
UF = uncertainty factor
MF = modifying factor
The UF is used to account for the extrapolation uncertainties (e.g., interindividual variation,
interspecies differences, duration of exposure, use of a LOAEL in place of a NOAEL), and
database adequacy. The MF is used as a judgment factor to account for the confidence in the
critical study (or studies) used in the derivation of the RfD (US EPA 2000).
The MCLG is then derived from the RfD as follows:
MCLG (mg/liter) = RfD x bw x RSC
I
where:
bw = body weight (70 kg for adults, 10 kg for children, 4 kg for infants);
RSC = relative source contribution, the fraction of the RfD allocated to drinking
water (to take into account exposure from other sources);
I = daily drinking water intake (2 liters for adults, 1 liter for children, 0.64 liter
for infants).
Generally, EPA assumes that the relative source contribution from drinking water is 20% of
the RfD, unless other exposure data for the chemical are available. The RSC is one factor that
will determine whether or not a change in the RfD will lead to a change in the MCLG.
It has also been the Agency policy to apply an additional safety factor to the RfD for
chemicals with equivocal evidence of carcinogenicity (Section 2.2). This practice is another
factor that must be evaluated to determine the impact of a change in RfD on the MCLG.
2.2. Assessment of Carcinogenicity
For drinking water contaminants regulated prior to the 1996 SDWA, OW followed a three-
category regulatory cancer classification system (Categories I, II, or III). These categories specify
decisions as to degree of concern for an agent's carcinogenic potential as a contaminant of
drinking water, and define to some extent the approach to risk management that is taken for
establishing MCLGs. Categories I, II, and III are designations not defined in guidelines but that
reflect OW policy.
EPA used the six alphanumeric categories (A, Bl, B2, C, D, E) of the 1986 cancer
guidelines (US EPA 1986) in establishing the MCLG. The six-group classification system is
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often equated to the three-category system in the NPDWR Federal Register announcements.
Table 1 describes the three categories and, with few exceptions (e.g., beryllium), their usual
equivalent alphanumeric classification. If a chemical is a known or probable human carcinogen
(Category I, generally Group A or B), the MCLG is generally set at zero because it is assumed,
in the absence of other data, that there is no known threshold for carcinogenicity. If a chemical
falls in Group C, a RfD approach along with an additional safety factor is used in deriving the
MCLG. The methodology used for establishing MCLGs for chemicals with varying degrees of
evidence of carcinogenicity is briefly described in Table 1.
Recent Agency assessments also use the 1996 Proposed Guidelines for Carcinogen Risk
Assessment (US EPA 1996) or the draft revised Guidelines for Carcinogen Risk Assessment (US
EPA 1999). The proposed and revised Guidelines use standard descriptors as part of the hazard
narrative to express the weight of evidence for carcinogenic hazard potential. The new
descriptors permit consideration of exposure route and mode of action when making an
assessment of carcinogenicity. The hazard descriptors of the 1996 proposed Guidelines, used in
this review cycle, are in three categories: "known/likely," "cannot be determined," and "not
likely." Subdescriptors are provided under these categories to further differentiate an agent's
carcinogenic potential. These hazard descriptors are given in the text whenever appropriate.
3. IDENTIFYING CANDIDATES FOR POSSIBLE REGULATORY REVISION
EPA will identify regulated chemical contaminants for which there have been changes in
the RfD and/or in cancer risk assessment from oral exposure. Such changes could result in a
change in the MCLG and MCL. Chemicals thus identified are considered candidates for
regulatory revision.
Health risk assessments completed under the following programs will be examined:
EPA Integrated Risk Information System (IRIS)
EPA Office of Pesticide Programs (OPP)
« National Academy of Sciences (NAS)
Agency for Toxic Substances and Disease Registry (ATSDR)
Table" 2 lists the 68 chemicals included in the 6-year review process, the RfDs and cancer
groups on which the MCLGs are based, those established by IRIS and OPP, and assessment
dates. IRIS dates are difficult to determine with any precision because of numerous sequential
revisions described in the "Revision History" for each substance. Dates of IRIS assessments are
approximate and refer to the most recent date when significant revisions were made to the RfD or
cancer assessment. Risk assessments conducted by IRIS and OPP can be found on EPA's Web
addresses www.epa.goy/iris/index.html and www.epa.gov/pesticides/reregistration/status.htm.
IRIS and OPP do not use the three-category approach for cancer hazard characterization,
but use the 1986 Cancer Guidelines and, recently, the 1996 Proposed Guidelines (US EPA 1986,
1996). For easy comparison, Categories I, II, and III on which the MCLGs are based have been
replaced by the equivalent cancer groups of the 1986 cancer guidelines (Table 1). If the oral and
Six-Year Review Draft Health Effects Technical Support Document February 2002
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inhalation cancer groups differ, the cancer groups given in Table 2 are those for oral exposure.
Whenever appropriate, the cancer hazard descriptors of the 1996 proposed cancer guidelines are
also given in Table 2.
As indicated in Table 2, NAS established in 1997 a tolerable upper intake level (UL) for
fluoride of 10 mg/day for children older than 8 years and for adults, based on protection against
skeletal fluorosis (NAS 1997). The 1997 NAS evaluation of fluoride does not have an impact on
the MCLG. In addition, recent assessments of copper and selenium by NAS (2000 a,b) do not
have an impact on the MCLGs for these two chemicals.
ATSDR establishes oral minimal risk levels (MRLs) for non-neoplastic endpoints for acute,
intermediate, and chronic exposure durations. MRLs for oral chronic exposure are similar to
EPA's RfDs. The chronic MRL for cadmium is the only .one among the chemicals under
consideration that is more recent than and different from the RfD established by IRIS and in the
regulation of 1991. As such, cadmium would qualify for possible revision. However, a new IRIS
assessment of cadmium is due in 2002 or 2003 (Table 3). Review of cadmium should therefore
await completion of the Agency's ongoing assessment. In summary, ATSDR completed
assessments do not have an impact on the selection of chemicals for potential revision during this
first 6-year review cycle.
Seven chemicals given in bold in Table 2 potentially qualify for revision, because of
different RfD and/or cancer groups postdating the MCLG. However, updated assessments for
alachlor (IRIS), diquat (OPP), and glyphosate (IRIS) are expected in 2002 or 2003 (Table 3).
Therefore, review of these three chemicals should await completion of the Agency's ongoing
assessments. The remaining four chemicals are potential candidates for additional consideration
and are listed below together with the latest assessment date.
Beryllium (IRIS 1998)
Chromium (IRIS 1998)
Oxamyl (OPP 2000)
Picloram (OPP 1998)
This tentative identification of chemicals potentially qualifying for revision was conducted
independently of other considerations (e.g., magnitude of gain in health protection, data gaps,
analytical and treatment technology, occurrence), which may influence the final selection of
contaminants to be revised.
For some chemicals with an MCLG of zero (chlordane, vinyl chloride), a change in RfD
postdating the regulation occurred in 1998 or later without a change in cancer group. These
chemicals do not potentially qualify for revision because, following Agency policy, the MCLG
for these chemicals will remain at zero, irrespective of any change in RfD.
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4. NOMINATION OF CHEMICALS FOR NEW RISK ASSESSMENT
4.1. Priority Chemicals of Potential Reproductive/Developmental Concern
With the passage of the SDWA and FQPA of 1996, a concerted effort was made by EPA to
take into account reproductive and developmental effects, and effects of chemicals on sensitive
subpopulations. However, contaminants under consideration in this first 6-year review cycle
were regulated in 1992 or earlier and might not have received adequate scrutiny for reproductive
and developmental effects. Accordingly, a literature search was conducted by EPA's Office of
Science and Technology (OST) to identify contaminants for which developmental and/or
reproductive effects might now appear to be the critical effects.1 Contaminants thus identified
will be nominated, as high priority for new Agency assessments.
New assessments by IRIS or OPP are ongoing for several chemicals included in this first 6-
year review cycle. Any reproductive or developmental effects of these chemicals will be taken
fully into consideration as part of these new assessments. Therefore, evaluation of the literature
search for reproductive/developmental effects was not considered useful for the 33 chemicals
listed below with ongoing IRIS (US EPA 2002b) or OPP assessments. Expected completion
years of these assessments are indicated below. If, upon completion of these new assessments, it
is determined that there is a potential impact on the MCLG, the chemicals in question will be
considered candidates for possible revision.
Acrylamide (IRIS, 2004/2005)
Alachlor (IRIS, 2002/2003)
Antimony (IRIS, 2002/2003)
Asbestos (miS, 2004/2005)
Atrazine (OPP, 2002)
Benzo[a]pyrene (IRIS, 2002/2003)
Cadmium (IRIS, 2002/2003)
Carbofuran (OPP, 2002/2003)
Carbon tetrachloride (IRIS, 2002/2003)
Copper (IRIS, 2002/2003)
2,4-D (OPP, 2003/2004)
Di(2-ethylhexyl)phthalate (IRIS, 2002/2003)
1,2-Dichlorobenzene (IRIS, 2002/2003)
1,4-Dichlorobenzene (IRIS, 2002/2003)
1,2-Dichloroethane (IRIS, 2002/2003)
1,1-Dichloroethylene (IRIS, 2002/2003)
Diquat (OPP, 2002)
Endothall (OPP, 2003/2004)
Ethylbenzene (IRIS, 2002/2003)
Ethylene dibromide (IRIS, 2002/2003)
Glyphosate (IRIS, 2002/2003)
Lindane (IRIS, 2003/2004)
Methoxychlor (OPP, 2002/2003)
Pentachlorophenol (IRIS, 2002/2003)
Polychlorinated biphenyls (IRIS, 2002/2003)
Simazine (OPP, 2003/2004)
Styrene (IRIS, 2002/2003)
2,3,7,8-TCDD (IRIS, 2002/2003)
Tetrachloroethylene (IRIS, 2002/2003)
Toluene (IRIS, 2002/2003)
1,1,1-Trichloroethane (IRIS, 2003/2004) '
Trichloroethylene (IRIS, 2002/2003)
Xylenes (IRIS, 2002/2003)
1 Critical effect is defined as the biologically significant adverse effect expected to occur at the lowest dose.
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Other chemicals are not under review by IRIS or OPP but have an MCLG of zero (Table 2).
Evaluation of the literature search was not considered useful for these chemicals because an
MCLG of zero is already protective of public health and will not be affected by new information
on reproductive or developmental effects. However, for chemicals not recently evaluated and
having a zero MCLG, EPA reviewed available information to inquire whether recent data show a
mode of action that implies nonlinearity of the dose-response. EPA did not find any data to
support such a mode of action (IARC, 1999, 2001; ATSDR, 1999). These 12 chemicals and the
year of the most recent Agency cancer assessments are given below.
Benzene (00) 1,2-Dichloropropane (91) Hexachlorobenzene (92)
Chlordane (98) Epichlorohydrin (92) Lead (91)
l,2-Dibromo-3-chloropropane (91) Heptachlor (92) Toxaphene (91)
Dichloromethane (92) Heptachlor epoxide (92) Vinyl chloride (00)
In addition, for chemicals with a nonzero MCLG, evaluation of the literature search for
reproductive and developmental effects was not considered necessary for new Agency
assessments finalized in 1997 or later. These assessments have considered reproductive and
developmental toxicity as a part of the evaluation. Agency assessments finalized in 1997 or later
are available for seven chemicals. These are barium (1998), beryllium (1998), chromium (1998),
hexachlorocyclopentadiene (2001), inorganic mercury (1997), oxamyl (2000), and picloram
(1998).
The following summarizes the process of identifying chemicals for which evaluation of the
literature search for reproductive and developmental effects is not necessary:
Number of
chemicals
33
12
Reason for not evaluating reproductive and
developmental literature searches
Ongoing assessments by IRIS or OPP \
Zero MCLG already protective of reproductive and
developmental effects, and no indication at this time for
nonlinearity of the dose-response relationship.
Nonzero MCLGs, recent (si997) Agency assessments
available.
The literature search for reproductive and developmental effects for the remaining 16
chemicals listed in Table 4 was evaluated. For various reasons briefly described in Table 4, RfDs
for three chemicalscyanide, di(2-ethylhexyl)adipate and thalliumcould be affected by new
information on developmental and/or reproductive toxicity. The small number of chemicals thus
identified is not surprising, as EPA's selection of contaminants for new IRIS or OPP assessment
is biased toward chemicals for which there is an indication that reproductive and/or
developmental effects may be of concern. In conclusion, three chemicals are high priority and, at
the request of OST, new IRIS risk assessments have been initiated for these chemicals. The new
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risk assessments are expected to be completed in the 2004/2005 time frame for cyanide,
2003/2004 for di(2-ethylhexyl)adipate, and 2004/2005 for thallium (US EPA 2002b).
4.2. Other Nominations for New Risk Assessment
As described above, the literature search for reproductive and developmental effects for 16
chemicals was evaluated. Three of these chemicals were identified as of potential reproductive or
developmental concern, and IRIS risk assessments were initiated in 2002. It was considered
desirable to determine, through a literature search for all other toxicological endpoints, if new
health effects information had become available for any of the remaining 13 chemicals, in which
case the chemical would be nominated for a new assessment.
Of the 13 chemicals under consideration, NAS conducted a recent assessment of selenium
(NAS 2000b). Therefore, selenium was eliminated from further consideration and a toxicological
literature search was conducted by OST for the remaining 12 chemicals. These are:
Dalapon
cis-1,2-Dichloroethylene
trans-1,2-Dichloroethylene
Dinoseb
Endrin
Fluoride (skeletal effects)
Monochlorobenzene
Nitrate
Nitrite
2,4,5-TP(Silvex)
1,2,4-Trichlorobenzene
1,1,2-Trichloroethane
There is new information on the effects of fluoride on bone and on the contribution of
various sources to total fluoride exposure (dental products, water, food, beverages, etc.). EPA
plans to request NAS to conduct a review of these data.
No new information was found for any of the remaining chemicals that could have an
impact on the MCLG. Accordingly, and for the tune being, these contaminants will not be
nominated for new assessments.
Because of considerable stakeholder interest in nitrate and nitrite, a more detailed rationale
for not considering these two chemicals as potential candidates for new IRIS assessments is
provided here. At the request of EPA, NAS evaluated the 1991 MCLGs and MCLs for nitrate
and nitrite. NAS evaluated the epidemiological and toxicological studies available for these
chemicals and concluded that EPA's current MCLGs and MCLs for nitrate and nitrite are
adequate to protect human health. NAS also concluded that exposure to nitrate/nitrite
concentrations found in drinking water in the United States is unlikely to contribute to human
cancer risk (NAS 1995). In 1997* California established Public Health Goals for nitrate and
nitrite hi drinking water identical to EPA's MCLGs and concluded that recent epidemiological
studies do not support an association between nitrate and nitrite exposure from drinking water
and increased cancer rates in humans (Cal/EPA 1997). More recently, the World Health
Organization (WHO) evaluated nitrate and nitrite and established the same "guideline values" for
these two chemicals as EPA's MCLGs, to protect against methemoglobinemia in bottle-fed
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infants below 3 months of age, the most susceptible segment of the population. WHO also
concluded that there is no evidence for an association between nitrite and nitrate exposure in
humans and the risk of cancer (WHO 1998).
A number of studies on nitrate and nitrite have become available since WHO's assessment
of 1998. Some of these studies that could possibly have an impact on the MCLGs are discussed
here. In an epidemiological study in Iowa, Weyer et al. (2001) found a positive relationship
between nitrate levels hi drinking water and risk of bladder and ovarian cancers, and an inverse
relationship for cancer of the uterine corpus and rectum. The authors recognized that additional
studies were needed before confirming these trends. Several limitations of the study were also
pointed out by the authors, including lack of information on individual water consumption and
poor characterization of the magnitude of exposure to nitrate, relatively small sample size for
bladder cancer, lack of information on occurrence of bladder infections, lack of information on
concomitant exposure to other contaminants in drinking water, including disinfection by-
products. No clear and consistent associations were found between increasing nitrate in drinking
water and non-Hodgkin's lymphoma, leukemia, or cancers of the colon, breast, lung, pancreas, or
kidney (Weyer et al. 2001). Other epidemiological studies of nitrate and/or nitrite and non-
Hodgkin's lymphoma (Ward et al. 1996), gastric, esophageal or brain cancer (Van Loon et al.
1998, Barrett et al. 1998) are also inconclusive. Several epidemiological studies of maternal
ingestion of nitrate in drinking water failed to confirm an association between nitrate exposure
and developmental effects hi offspring (e.g., Croen et al. 1997).
There are differing views on the role of nitrate/nitrite versus gastrointestinal infections as
the cause of infant methemoglobinemia (Avery 1999, Knobeloch et al. 2000). It is recognized
that bottle-fed infants have a high probability of developing GI infections because of their low
gastric acidity. It is also recognized that GI infections and low acidity enhance the conversion of
nitrate to nitrite and methemoglobin formation in infants. This is an additional reason for
considering these infants as a high-risk group for developing methemoglobinemia from exposure
to nitrate/nitrite (WHO 1998).
NTP carried out toxicology and carcinogenesis studies of sodium nitrite (NTP 2001). There
was no evidence of carcinogenic activity of sodium nitrite in male or female rats, rior in male
mice. There was equivocal evidence of carcinogenic activity hi female mice based on a positive
trend in the incidences of squamous cell papilloma or carcinoma (combined) of the forestomach.
Given these conclusions, a change in the cancer assessment of nitrite is not warranted at this
time.
The outcome of the review of nitrate and nitrite indicates that the basis of the current
MCLGs for these two chemicals remain appropriate and, therefore, we are not nominating nitrate
or nitrite for new IRIS assessments at this time.
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5. SUMMARY
All conclusions reached in this document should be considered tentative pending receipt of
public comments.
Four chemicals have been identified as potentially qualifying for revision on the basis of
new IRIS or OPP health assessments that could impact the MCLG. These are beryllium,
chromium, oxamyl, and picloram. This tentative identification of chemicals potentially
qualifying for revision was conducted independently of other considerations (e.g., analytical and
treatment technology, magnitude of gain in health protection, data gaps, occurrence), which may
influence the final selection of contaminants to be revised.
Three chemicals, cyanide, di(2-ethylhexyl)adipate, and thallium, are high priority because
of reproductive and/or developmental concerns. New IRIS health assessments of these chemicals
have been initiated. The new risk assessments are expected to be completed in the 2004/2005
time frame for cyanide, 2003/2004 for di(2-ethylhexyl)adipate, and 2004/2005 for thallium (US
EPA2002b).
New data have become available regarding the effect of fluoride on bone, and the
contribution of various sources to total fluoride exposure. EPA plans to request NAS to conduct
a review of these data.
Table 5 provides the details of the review process applied to each of the 68 chemicals under
consideration.
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6. REFERENCES
ATSDR (Agency for Toxic Substances and Disease Registry). 1992. Toxicologies! Profile for Thallium. Available
at: www.atsdr.oic.gov/toxpro2.htmlS-A-
ATSDR. 1996. Toxicological Profile for Selenium. Available at: www.atsdr.cdc.gov/toxpro2.html#-A-
ATSDR. 1997. Toxicological Profile for Cyanide. Available at: www.atsdr.cdc.'gov/toxpro2.html#-A-
ATSDR. 1999. Toxicological Profile for Lead. Available at: www.atedr.cdc.gov/toxpro2.htmW-A-
Avery AA 1999. Infantile methemoglobinemia: Reexamining the role of drinking water nitrates. Environ Health
Perspect 107(7):583-586.
Barrett JH, Parslow RC, McKinney PA et al. 1998. Nitrate in drinking water and the incidence of gastric,
esophageal, and brain cancer in Yorkshire, England. Cancer Causes Control 9:153-159.
Cal/EPA (California Environmental Protection Agency). 1997. Public health goals for nitrate and nitrite in drinking
water. December 1997. Available at: http:/Avww.oehha.ca.gov/water/phg/allphgs.html
Cal/EPA. 1999. Public health goals for thallium in drinking water. December 1997. Available at:
http:/Avww.oebha.ca.gov/water/phg/allphgs.html. '
ChapinR, Gulati D, Barnes LH. 1997. Sodium nitrite. Environ Health Perspect 105 (Suppl 1).
Croen LA TodoroffK, Shaw GM. 1997. Maternal dietary nitrate exposure and risk for neural tube defects. Am J
Epidemiol 145:830.
EC (European Commission). 1999. European Commission Scientific Committee on Toxicity, Ecotoxicity and the
Environment: Opinion on the toxicological characteristics and risks of certain citrates and adipates used as a
substitute for phthalates as plasticisers in certain soft PVC products. 28 September 1999. Brussels, Belgium.
IARC (International Agency for Research on Cancer). 1999. IARC Monographs on the Evaluation of Carcinogenic
Risks to Humans, Re-evaluation of Some Organic Chemicals, Hydrazine and Hydrogen Peroxide. Vol. 71.1,2-
Dibromo-3-chloropropane, pp. 479-500; Dichloromethane, pp. 251-315; 1,2-Dichloropropane, pp. 1393-1400;
Epichlorohydrin, pp. 603-628. Lyon, France.
IARC. 2000. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Some Industrial Chemicals.
Lyon, France. Vol. 77: Di(2-ethylhexyl)adipate, pp. 149-175. Lyon, France.
IARC. 2001. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Some Thyrotropic Agents. .
Vol. 79: Chlordane and heptachlor, pp. 411 -492; Hexachlorobenzene, pp. 493-568; Toxaphene, pp. 569-604. Lyon,
France.
Knobeloch L, Salna B, Hogan A et al. 2000. Blue babies and nitrate-contaminated well water. Environ Health
Perspect 108(7):675-678.
NAS (National Academy of Sciences). 1995. Nitrate and nitrite in drinking water. Washington, DC :National
Academy Press.
NAS. 1997. Dietary reference intakes for calcium, phosphorus, magnesium, vitamin D, and fluoride. Washington,
DC: National Academy Press.
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NAS. 2000a. Copper in drinking water. Washington, DC: National Academy Press, Washington, DC.
NAS. 2000b. Dietary reference intakes for vitamin C, vitamin E, selenium, and carotenoids. Washington, DC:
National Academy Press.
NDWAQ (National Drinking Water Advisory Council). 2000. Recommended guidance for review of existing
national primary drinking water regulations, November 2000.
NTP (National Toxicology Program). 1993. Toxicity studies of sodium cyanide, (CAS No. 143-33-9) administered
by dosed water to F344/N rats and B6C3F1 mice.
NTP. 1996. Sodium selenate (rats), CAS No. 13410-01-0). Study number: RDGT 94011. May 1, 1996.
NTP. 2001. TR-495. Toxicology and carcinogenesis studies of sodium nitrite (CAS No. 7632-00-00) in F344/N
rats and B6C3F, mice.
US EPA. 1986. Guidelines for carcinogen risk assessment. FRVol. 51, No. 185: 33992-34003. September 24,
1986. Available at: http://cfbub.epa.gov/ncea/cfm/cancer.cfm?ActType=default.
US EPA. 1989. National primary and secondary drinking water regulations; Proposed Rule. FR Vol. 54, No. 97:
22062-22094. May 22, 1989.
US EPA. 1991. National primary drinking water regulations; Final Rule. FR Vol. 56, No. 20: 3526-3597. January
30,1991.
US EPA. 1996. Proposed guidelines for carcinogen risk assessment. FRVol. 61, No. 79: 17960-18011. April 23,
1996. Available at: http://cfpub.epa.gov/ncea/cfm/cancer.cfm?ActType=default.
US EPA. 1997. Mercury Study Report to Congress. December 1997. Office of Air Quality Planning & Standards
and Office of Research and Development. EPA-452/R-97-009. Available at:
http://www.epa.gov/ttncaaal/t3/reports/volume5.pdf.
US EPA. 1999. Guidelines for carcinogen risk assessment. NCEA-F-0644 Review Draft. July 1999. US EPA
Risk Assessment Forum. Washington DC.
US EPA. 2000. EPA Summary Report. Characterization of data variability and uncertainty: Health effects
assessments in the Integrated Risk Information System (IRIS). In response to Congress, HR 106-379. National
Center for Environmental Assessment, Office of Research and Development, Washington, DC. EPA/635/R-
00/005F. Available at: http://www.epa.gov/ncea/pdfs/iris/ncea_repf.pdf.
US EPA. 2002a. EPA Protocol for review of existing national primary drinking water regulations. Office of
Ground Water and Drinking Water.
US EPA. 2002b. Integrated Risk Information System (IRIS); Announcement of 2002 Program; Request for
information. FR Vol. 67, No. 6:1212-1215. January 9,2002. Available at: http://www.epa.gov/fedrgstr/EPAFR-
CONTENTS/2002/January/Day-09/contents.htm.
Van Loon AJ, Botterweck AA, Goldbohm RA, et al. 1998. Intake of nitrate and nitrite and the risk of gastric
cancer: A prospective cohort study. Br J Cancer 78:129-135.
Ward MH, Mark SD, Cantor KP, et al. 1996. Drinking water nitrate and the risk of non-Hodgkin's lymphoma.
Epidemiology 7:465-471.
Six-Year Review Draft Health Effects Technical Support Document February 2002 11
-------
Weyer PJ, Cerhan JR, Cross BC, et al. 2001. Municipal drinking water nitrate level and cancer risk in older
women: the Iowa Women's Health Study. Epidemiology 12(3):327-338.
WHO (World Health Organization). 1996. Guidelines for drinking-water quality, 2nd ed. Vol2: Health criteria
and other supporting information. Geneva, Switzerland. Available at:
http://ww\v.who.int/water_sanitation_health/GDWQ/Chemicals/Chemlist.html.
WHO. 1998. Guidelines for drinking-water quality, 2nd ed. Addendum to Vol. 1: Recommendations. Geneva,
Switzerland. Available at: http://www.who.int/water_sanitation_health/GDWQ/Chemicals/Chemlist.html.
WHO. 2002. World Health Organization. Environmental Health Criteria No. 227: Fluorides. Summary and
Conclusions. Geneva, Switzerland. Available at: http://www.who.int/pcs/pcs_new.html.
12 Six-Year Review Draft Health Effects Technical Support Document February 2002
-------
Table 1. Cancer classification systems used by EPA (US EPA 1986,1989, 1991)
Three-category approach for
establishing MCLGs
Corresponding five-group classification
system of 1986 cancer guidelines
generally set a^zero
Category I:
Known or probable human
carcinogens: Strong evidence of
carcinogenicity
Sufficient human or animal evidence of
carcinogenicity.
Generally Group A or B
A: Human carcinogen
Sufficient evidence from epidemiological studies
to support a causal association.
B: Probable human carcinogen
El: Limited evidence of carcinogenicity from
epidemiological studies.
B2: Inadequate evidence or no data from
epidemiological studies; sufficient evidence from
animal studies.
TVICLG based
-------
Table 2. Chemicals considered under the first six-year review cycle
(New RfD and/or cancer assessment have become available for seven chemicals given in bold).
-pr,:.";:,.!'>i|||.
:f"^ :,4 ;||!
1. Acrylamide
2. Alachlor
3. Antimony
4. Asbestos (fibers > 10
um in length)
5. Atrazine
6. Barium
7. Benzene
8. Benzo[a]pyrene
fSSfii
0
(1/91)
0
(1/91)
0.006
(7/92)
7 MFL
(1/91)
0.003
(1/91)
2
(7/91)
0
(7/87)
0
(7/92)
v-^ s x^ ^\ v ^ "^
is&'
TT
0.002
0.006
7MFL
0.003
(1/91)
2
0.005
0.0002
^ '''ifeWk \
&~.\
0.0002
0.01
0.0004
0.005
0.07
-
,'V -'- 5::
Shv;
B2
B2
D
C2
C
D
A
B2
- , "HKH-I.
sX s %
0.0002
(91)
0.01
(93)
0.0004
(91)
NA
0.035
(93)
0.07
(98)
NA
NA
^ ;::;;]
tr?|
B2
(91)
NA
NA
3
(88)
NA
D4
(98)
A5
(00)
B2
(92)
: ',$«$*?
0.01
(9/98)
\*&****> \
^;:
(9/98)
Using the 1996 proposed cancer guidelines, alachlor is likely to be carcinogenic to humans at high doses,
but not likely at low doses.
2 Group C based on limited, evidence of carcinogenicity by the oral route (US EPA 1989). Group A by
inhalation exposure.
3 Limited animal evidence for carcinogenicity via ingestion, and epidemiologic data in this regard are
inadequate. Group A by inhalation exposure.
Using the 1996 proposed cancer guidelines, barium is considered not likely to be carcinogenic to humans
following oral exposure.
Using the 1996 proposed cancer guidelines, benzene is characterized as a known human carcinogen for all
routes of exposure.
14 Six-Year Review Draft Health Effects Technical Support Document February 2002
-------
Table 2 (continued)
., -^K'^
£ , *'...«.'... **.' %
Cltewical'i "~- «"" ' "",
A x ^ / ^
9. Beryllium
10. Cadmium
11. Carbofuran
12. Carbon tetrachloride
13. Chlordane
14. Chromium
(total)
Cr(VI)
Cr (III)
«[, , - RefflHationXnionfli/yjear) "J
, ,;Ki~ ^ *^ "V $»£«**. ^
'«GMr/v
mg/L^t
0.004
(7/92)
0.005
(1/91)
0.04
(1/91)
0
(7/87)
0
(1/91)
0.1
(1/91)
Wc4 : --
»%/£'
0.004
0.005
0.04
0.005
0.002
0.1
' £>Sf
-------
Table 2 (continued)
Chemical
15. Copper
16. Cyanide
17. 2,4-D (2,4-
Dichlorophenoxyacetic
acid)
18. Dalapon(2,2-
Dichloropropionic acid)
19. Di(2-ethylhexyl)
adipate
20. Di(2-ethylhexyl)
phthalate
21. l,2-Dibromo-3-
chloropropane (DBCP)
22. Dichlorobenzene o-
(1 ,2-Dichlorobenzene)
23. Dichlorobenzene p-
( 1 ,4-Dichlorobenzene)
24. Dichloroethane(l.,2-)
(Ethylene dichloride)
25. Dichloroethylene
0,1-)
26. Dichloroethylene
(cis-1,2-)
27. Dichloroethylene
(trans- 1,2-)
28. Dichloromethane
(methylene chloride)
29. Dichloropropane
0»
Regulation (month/year) .
MCLG,
mg/L
1.3 12
(6/91)
0.2
(7/92)
0.07
(1/91)
0.2
(7/92)
0.4
(7/92)
0
(7/92)
0
(1/91)
0.6
(1/91)
0.075
(7/87)
0
(7/87)
0.007.
(7/87)
0.07
(1/91)
0.1
(1/91)
0
(7/92)
0
(1/91)
MCI,
tng/L
TT12
0.2
0.07
0.2
0.4
0.006
0.0002
0.6
0.075
0.005
0.007
0.07
0.1
0.005
0.005
Rfl> -
mg/kg/d
0.02
0.01
0.03
0.6
0.02
0.09
0.1
0.009
0.01
0.02
0.06
Cancer
D
D
D
D
C
B2
B2
D
C
B2
C
D
D
B2
B2
; .juusti
Kfb
NA
0.02
(87)
0.01
(87)
0.03
(88)
0.6
(92)
0.02
(88)
NA
(91)
0.09
(90)
NA
(94)
NA
0.009
(89)
NA
0.02
(88)
0.06
(91)
NA
(91)
JtIM I"*! * '/
CtfDcerj:
grp. /-
D
(88)
D
NA
NA
C
(92)
B2
(88)
NA
D
(90)
NA
B2
(91)
C
(98)
D
(90)
NA
B2
(91)
NA
/
f£
-------
Table 2 (continued)
V* V . .
V % % S ^ " %% SW.TV. .-^
30. Dinoseb
31. Diquat
32. Endothall
33. Endrin
34. Epichlorohydrin
35. Ethylbenzene
36. Ethylene dibromide
(EDB; 1,2-Dibromoeth-
ane)
37. Fluoride 13
38. Glyphosate
39. Heptachlor
40. Heptachlor epoxide
s; ^vi^^W^^f^tv^T-;^
^l~
0.007
(7/92)
0.02
(7/92)
0.1
(7/92)
0.002'
(7/92)
0
(1/91)
0.7
(1/91)
0
(1/91)
4.0
(11/85)
0.7
(7/92)
0
(1/91)
0
(1/91)
£*H
0.007
0.02
0.1
0.002
TT
0.7
,0.00005
4.0
(4/86)
0.7
0.0004
0.0002
fSwil
0.001
0.0022
0.02
0.0003
NA
0.1
0.11 14
0.1
0.0005
0.000013
*&*
D
D
D
D
B2
D
B2
D
B2
B2
: -<«^»§ ^; i
^i
0.001
(89)
0.0022
(87)
0.02
(87) .
0.0003
(89)
NA
0.1
(91) '
NA
0.0615
0.1216
(87)
0.1
(89)
0.0005
(91)
0.000013
(91)
S#3
D
(89)
NA
NA
D
(89)
B2
(92)
D
(91)
B2
(91)
NA
D
(89)
B2
(91)
B2
(91)
^^^§^v
Canceled
0.005
(3/95)
Canceled
Canceled
2
(9/93)
0.0005
(92)
,0.000013
(92)
. ^ *-.-. "'' % % \ "
E
(3/95)
E '
(9/93)
B2
(92)
B2
(92)
13 -
NAS (1997) established a tolerable upper intake level (UL) for fluoride of 10 mg/day for children older
than 8 years and for adults, based on protection against skeletal fluorosis. The 1997 NAS evaluation of fluoride does
not affect the MCLG. .
14-
This is the RfD calculated from the MCLG assuming 70kg body weight and intake of 2L/day. The
MCLG was developed from a lowest effect level for crippling skeletal fluorosis of 20mg/day with continuous
exposures over a 20-year or longer period. The LOAEL was divided by an uncertainty factor of 2.5 and a drinking
water intake of 2L/day to obtain the MCLG.
15
16
For objectionable dental fluorosis, a cosmetic effect.
For crippling skeletal fluorosis in humans.
Six-Year Review Draft Health Effects Technical Support DocumentFebruary 2002
17
-------
Table 2 (continued)
Chemical
41. Hexachlorobenzene
42. Hexachlorocyclo-
pentadiene
43. Lead
44. Lindane (y-hexa-
chlorocyclohexane)
45. Mercury (Inorganic)
46. Methoxychlor
47. Moriochlorobenzene
(Chlorobenzene)
48. Nitrate (as N)
49. Nitrite (as N)
Nitrate + Nitrite (as N)
Regulation (month/year) *
MCLG,
mg/L
0
(7/92)
0.05
(7/92)
0
(6/91)
0.0002
(1/91)
0.002
(1/91)
0.04
(1/91)
0.1
(1/91)
10
(1/91)
1
(1/91)
10
(1/91)
MCL,
mg/L
0.001
0.05
TT19
0.0002
.0.002
0.04
0.1
10
1
10
RfD
mg/kg/d '
0.0008
0.007
0.0003
0.0003
0.005
0.02
1.6 21
0.16 21
Cancer
grp,
B2
D
B2
C
D
D
D
D
D
^ ' IRIS (year): /
'Rfl>." ";
0.0008
(91)
0.006 "
(01)
NA
0.0003
(88)
0.0003 20
(97)
0.005
(90)
0.02
(90)
1.621
(91)
O.I22
(87)
* <
Cancer,
grp^ A
B2
(91)
18
(01)
B2
(88)
NA
20
(97)
D
(90)
D
(90)
NA
NA
, OPP (ttfonth&ear)
M>~','
ntg/kgtf "
Canceled
Cancer
8W
17 RfD based on the same toxicological study as that of the MCLG but using benchmark dose modeling for
the dose-response analysis.
18 E by inhalation exposure. The potential for carcinogenicity by the oral route is unknown.
19 Lead action level: 0.015 mg/L.
20 Mercury Study Report to Congress assessment (US EPA 1997): RfD for inorganic Hg of 0.0003
mg/kg/day retained. Using the 1996 proposed cancer guidelines, inorganic mercury is not likely to be a human
carcinogen at levels found in water.
21 RfD in mg N/kg/day back-calculated from epidemiological studies on the basis of 0.64 L/day and a 4-kg
infant.
RfD in mg N/kg/day back-calculated from epidemiological studies on the basis of 1 L/day and a 10-kg
child. It is equivalent to a RfD of 0.16 mg/kg/day if 0.64 L/day and a 4-kg infant were used.
18
Six-Year Review Draft Health Effects Technical Support Document February 2002
-------
Table 2 (continued)
sP-sit/ £, ,.>, , ^
-;-. , > -i
CJiemtealf \^ «
50. Oxamyl (Vydate)
51. Pentachlorophenol
52. Picloram
53. Polychlorinated
biphenyls (Aroclors)
54. Selenium23
55. Simazine
56. Styrene
57. 2,3,7,8-TCDD
(Dioxin)
58. Tetrachloroethylene
("perc")
59. Thallium
60. Toluene
61. Toxaphene
62. 2,4,5-TP (Silvex;
2,4,5-Trichloroplien-
oxypropionic acid)
63. Trichlorobenzene
(1,2,4-)
64. Trichloroethane
(1,1,1-)
~, ,"-^RegBlation'(,inonth/year)3'*t-) *
I'MGLG^
'mg/L'f^
0.2
(7/92)
0
(1/91)
0.5
(7/92)
0
(1/91)
0.05
(1/91)
0.004
(7/92)
0.1
(1/91)
0
(7/92)
0
(1/91)
0.0005
(7/92)
1 .
(1/91)
0
(1/91)
0.05
(1/91)
0.07
(7/92)
0.20
(7/87)
'AK3, %
mg/L ' *
0.2
0.001
0.5
0.0005
0.05
0.004
0.1
3x1 0-s
0.005
0.002
1
0.003
0.05
0.07
0.20
**"*.
Mm^kg/d, /}
0.025
0.03
0.07
0.005
0.005
0.2
io-9
0.01
0.00007
0.2
NA
0.008
0.01
0.035
"Cancer **
^ , ,
E
B2
D
B2
D
C
C
B2
B2
D
D
B2
D
D
D
1 JlRIS^jar/
1P>
, ' " ' //
0.025
(87)
0.03
(91)
0.07
(87)
2-7 xlO'5
(96)
0.005
(91)
0.005
(93)
0.2
(90)
0.01
(88)
0.00008
(90)
0.2
(90)
NA
0.008
(88)
0.01
(92)
NA
(91)
Cto&CKte ~
$W* - ;
NA ,
B2
(91)
NA
B2
(96)
D
(91)
NA
NA
NA
D
(90)
D
(90)
B2
(91)
D
(88)
D
(91)
D
(9.0)
"' OPP (month/year)-.
RfD, £
mj/$g/d
0.001
(10/00)
0.20
(4/98)
Canceled
Canceled
Canceled
Canceled
&
^Cancer "
w-^. '
E
(10/00)
E
(4/98)
23 NAS (2000b) tolerable upper intake level (UL) for selenium for adolescents and adults is 0.4 mg/day, a
value equivalent to the RfD of 0.005 mg/kg/day established in 1991.
Six-Year Review Draft Health Effects Technical Support Document February 2002
19
-------
Table 2 (continued)
Chemical
65. Trichloroethane
(1,1,2-)
66. Trichloroethylene
67. Vinyl chloride
68. Xylenes (total)
Regulation (month/year) -< Vv «
A«?£G,
mg/L
0.003
(7/92)
0
(7/87)
0
(7/87)
10
(1/91)
MCI,
mg/L
0.005
0.005
0.002
10
KfD
mg/kg/d
0.004
2
Cancer
8W'
C
B2
A
D
IRIS (year) , .,
?&> ''\
* * -
C
(91)
NA
(89)
A24
(00)
D
(88)
t»PP (month/year)'
Rfl>
Mtg/kgM
Canceled
Canceled
Cttacar
WP-;/ t
24 Using the 1996 proposed cancer guidelines, VC is a known human carcinogen by the inhalation route of
exposure, based on human epidemiological data, and by analogy the oral route because of positive animal bioassay
data as well as pharmacokinetic data allowing dose extrapolation across routes.
20
Six-Year Review Draft Health Effects Technical Support Document February 2002
-------
I
I
cs
I
tJ
c
IS
c
o
cj
so
"cs
J*1
«s
^g>
.
"§J
SJ
- -
;
-
v^
S'
1
"|-
on
%
C/3
> i
Acrylamide '9
S
PH
o<
O
00
Alachlor '91
S
Pi
p
00
oo
Antimony '92
1
oo
2
Pi
p
p
<
Asbestos '91
Pi
Q
oo oo
oo
Atrazine '91
00
s
g
<
t I
ON
1
00
2
i i
pi
p
oo
H
Benzene '87
Pi
Q
oo oo
Pi
p
{2
^
00
2
H- <
CN
Os
fl\
Benzo[a]pyren
P4
P
00
2
pi
p
00 .
H
i
oo
2
Pi
p
<
00
Cadmium '91
%
Carbofuran '91
oo
Pi
H
<
00
r-
00
-l
1
d
s
§
Ci
i
I
s
I
-a
I
!
1
-------
I
n
.2
2
^
s
%
o\
ON
g
^
S
»
S
00
00
Pi
p
GO GO
H <
< 2
Fluoride '86
-------
§
.x^
p-
s^
/r
*'J
J ^ ^
*"j"--S!
§s
OS
i
- IS,^
0\
/> ,
' ' SJ
s
i
:5K
-
a
,
,
s
f»K
^,
a*
^
Ov
-',
, ^v^-
7^-
'fee
-if
J-
^
&
CLj
OH
o
Glyphosate '92
Pi
Q
CO
H
»
OS
OS
5-
pa
0
O
§
£
o
I
do
E2J
t
^
«
£
^
2 Q
i
fr
pi
s
CO
l
^
la
I
I
i
-------
a
C3
H
'a
^
«S
O,
s
K,
$
^
s
s
s
s
§
Cliemicalf Year Regulated
^
oo
oo
HH ^^
P ^
1
-------
Table 4. Evaluation of the literature search for reproductive and developmental toxicity
(New IRIS assessments initiated for chemicals given in bold)
Clttamictg^ '* ^'~'
Cyanide
Dalapon
Di(2-ethylhexyl)adipate
cis- 1 ,2-Dichloroethylene
trans- 1,2-
Dichloroethylene
Dinoseb
Endrin
Fluoride
Monochlorobenzene
Nitrate
C0itoiients^ 3 '* s) , ' ~" ,i~. »- t -- >""" "« ,"-, V- t"^ """iC r«
Based on NTP (1993) 13-week study, ATSDR (1997) identified a NOAEL of 4.5
mg/kg/day for reproductive effects in male rats (decreases in epididymis and testis
weights and reduction in spermatid head size and count). The current 1992
NPDWR RfD of 0.02 mg/kg/day is based on a NOAEL of 10.8 mg/kg/day in a 2-
year study for weight loss, thyroid effects and myelin degeneration in rats. New
IRIS assessment initiated.
New information does not support need to revise RfD/MCLG
Current RfD/MCLG of 1992 based on a developmental toxicity study in rats that
identified a NOAEL of 170 mg/kg/day. WHO (1996) and the European
Commission (EC, 1999) considered the LOAEL to be 170 mg/kg/day and the
NOAEL to be the next lower dose of 28 mg/kg/day. Similarly, IARC (2000)
indicated effects at 170 mg/kg/day. New IRIS assessment initiated to reevaluate the
available developmental and reproductive studies, and to evaluate new studies that
have become available on the toxicity of DEHA and its metabolites.
New information does not support need to revise RfD/MCLG.
New information does not support need to revise RfD/MCLG.
Current RfD based on three-generation reproductive study in rats. Developmental
effects seen at higher doses than are reproductive effects. New information does not
support need to revise RfD/MCLG.
Reproductive and developmental effects occur at doses above those causing
hepatotoxicity, the critical effect New information does not support need to revise
RfD/MCLG.
No new studies identified in the literature search indicating that fluoride adversely
affects reproductive or developmental endpoints. Epidemiological studies show no
evidence of an association between the consumption of fluoridated drinking water
by mothers and increased risk of spontaneous abortion or congenital malformation
(WHO, 2002).
New information does not support need to revise RfD/MCLG.
Current RfD/MCLG established to protect infants, the most susceptible segment of
the population. Epidemiological studies of maternal nitrate exposure from drinking .
water and developmental effects in offspring or spontaneous abortion are
inconclusive (Croen et al. 1997). Reproductive and developmental effects in
experimental animals are not the critical effects. Epidemiological studies of nitrate
in drinking water and cancer incidence, including non-Hodgkin's lymphoma, a
childhood cancer, and bladder cancer are inconclusive (Weyer et al. 2001; Ward et
al. 1996). New information does not support need to revise RfD/MCLG.
Six-Year Review Draft Health Effects Technical Support Document February 2002
25
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Table 4 (continued)
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