Final Public Health Goal for Arsenic in Drinking Water

234 Pages·2004·0.92 MB·English

PUBLIC HEALTH GOALS FOR
CHEMICALS IN DRINKING WATER

ARSENIC

April 2004

Governor of the State of California
Arnold Schwarzenegger

Secretary for Environmental Protection
California Environmental Protection Agency

Terry Tamminen

Director

Office of Environmental Health Hazard Assessment
Joan E. Denton, Ph.D.
Public Health Goal for
ARSENIC
in Drinking Water

Prepared by

Office of Environmental Health Hazard Assessment
California Environmental Protection Agency

Pesticide and Environmental Toxicology Section
Anna M. Fan, Ph.D., Chief

Deputy Director for Scientific Affairs
George V. Alexeeff, Ph.D.

April 2004
LIST OF CONTRIBUTORS

PHG PROJECT REPORT SUPPORT
MANAGEMENT PREPARATION

Project Director Primary Author Administrative Support
Anna Fan, Ph.D. Joseph Brown, Ph.D. Edna Hernandez
Coordinator
Public Workshop Contributing Author Sharon Davis
Robert Howd, Ph.D. Lauren Zeise, Ph.D. Hermelinda Jimenez
Juliet Rafol Genevieve Vivar
Primary Reviewers
Coordination of Jay Beaumont, Ph.D. Library Support
External Review Martha Sandy, Ph.D. Charleen Kubota, M.L.S.
Moira Sullivan, M.S. .

Revisions/Responses Final Reviewers Web site Posting
Robert Howd, Ph.D. Robert Howd, Ph.D. Laurie Monserrat
Anna Fan, Ph.D.
George Alexeeff, Ph.D.

We acknowledge the contributions of Drs. Allan Smith and Nancy Lopipero of the
University of California at Berkeley, who prepared a large portion of the
epidemiological section and quantitative risk assessment under contract with the
Office of Environmental Health Hazard Assessment.

We thank the U.S. Environmental Protection Agency (Office of Water; National
Center for Environmental Assessment) and the faculty members of the University of
California with whom the Office of Environmental Health Hazard Assessment
contracted through the University of California Office of the President for their peer
reviews of the public health goal documents, and gratefully acknowledge the
comments received from all interested parties.
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PREFACE
Drinking Water Public Health Goals
Pesticide and Environmental Toxicology Section
Office of Environmental Health Hazard Assessment
California Environmental Protection Agency

This Public Health Goal (PHG) technical support document provides information on
health effects from contaminants in drinking water. PHGs are developed for
chemical contaminants based on the best available toxicological data in the scientific
literature. These documents and the analyses contained in them provide estimates of
the levels of contaminants in drinking water that would pose no significant health
risk to individuals consuming the water on a daily basis over a lifetime.
The California Safe Drinking Water Act of 1996 (amended Health and Safety Code,
Section 116365), amended 1999, requires the Office of Environmental Health
Hazard Assessment (OEHHA) to perform risk assessments and publish PHGs for
contaminants in drinking water based exclusively on public health considerations.
Section 116365 specifies that the PHG is to be based exclusively on public health
considerations without regard to cost impacts. The Act requires that PHGs be set in
accordance with the following criteria:
1. PHGs for acutely toxic substances shall be set at levels at which no known or
anticipated adverse effects on health will occur, with an adequate margin of
safety.
2. PHGs for carcinogens or other substances that can cause chronic disease shall
be based upon currently available data and shall be set at levels that OEHHA
has determined do not pose any significant risk to health.
3. To the extent the information is available, OEHHA shall consider possible
synergistic effects resulting from exposure to two or more contaminants.
4. OEHHA shall consider the existence of groups in the population that are
more susceptible to adverse effects of the contaminants than a normal healthy
adult.
5. OEHHA shall consider the contaminant exposure and body burden levels that
alter physiological function or structure in a manner that may significantly
increase the risk of illness.
6. In cases of insufficient data to determine a level of no anticipated risk,
OEHHA shall set the PHG at a level that is protective of public health with
an adequate margin of safety.
7. In cases where scientific evidence demonstrates that a safe dose-response
threshold for a contaminant exists, then the PHG should be set at that
threshold.
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8. The PHG may be set at zero if necessary to satisfy the requirements listed
above.
9. OEHHA shall consider exposure to contaminants in media other than
drinking water, including food and air and the resulting body burden.
10. PHGs published by OEHHA shall be reviewed every five years and revised
as necessary based on the availability of new scientific data.
PHGs published by OEHHA are for use by the California Department of Health
Services (DHS) in establishing primary drinking water standards (State Maximum
Contaminant Levels, or MCLs). Whereas PHGs are to be based solely on scientific
and public health considerations without regard to economic cost considerations,
drinking water standards adopted by DHS are to consider economic factors and
technical feasibility. Each standard adopted shall be set at a level that is as close as
feasible to the corresponding PHG, placing emphasis on the protection of public
health. PHGs established by OEHHA are not regulatory in nature and represent only
non-mandatory goals. By federal law, MCLs established by DHS must be at least as
stringent as the federal MCL if one exists.
PHG documents are used to provide technical assistance to DHS, and they are also
informative reference materials for federal, state and local public health officials and
the public. While the PHGs are calculated for single chemicals only, they may, if the
information is available, address hazards associated with the interactions of
contaminants in mixtures. Further, PHGs are derived for drinking water only and are
not intended to be utilized as target levels for the contamination of other
environmental media.

Additional information on PHGs can be obtained at the OEHHA Web site at
www.oehha.ca.gov.

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TABLE OF CONTENTS
LIST OF CONTRIBUTORS..................................................................................III
PREFACE................................................................................................................IV
TABLE OF CONTENTS........................................................................................VI
PUBLIC HEALTH GOAL FOR ARSENIC IN DRINKING WATER................1
SUMMARY.................................................................................................................1
INTRODUCTION......................................................................................................2
CHEMICAL PROFILE.............................................................................................4
Chemical Identity..............................................................................................4
Physical and Chemical Properties....................................................................5
Production and Uses.........................................................................................5
Sources..............................................................................................................6
ENVIRONMENTAL OCCURRENCE AND HUMAN EXPOSURE...................6
Air.....................................................................................................................6
Soil....................................................................................................................7
Water.................................................................................................................7
Food..................................................................................................................9
Other Sources..................................................................................................10
METABOLISM AND PHARMACOKINETICS..................................................10
Absorption......................................................................................................10
Distribution.....................................................................................................12
Metabolism.....................................................................................................12
Excretion.........................................................................................................17
Physiologically-Based Pharmacokinetic (PBPK) Models..............................19
Physiological/Nutritional Role.......................................................................20
TOXICOLOGY........................................................................................................21
Toxicological Effects in Animals and Plants..................................................21
Acute Toxicity..........................................................................................21
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Subchronic Toxicity..................................................................................22
Genetic Toxicity.......................................................................................23
Developmental and Reproductive Toxicity..............................................29
Immunotoxicity.........................................................................................35
Neurotoxicity............................................................................................36
Biochemical and Cellular Toxicity...........................................................37
Chronic Toxicity.......................................................................................40
Carcinogenicity.........................................................................................41
Toxicological Effects in Humans...................................................................47
Acute Toxicity..........................................................................................47
Subchronic Toxicity..................................................................................47
Genetic Toxicity.......................................................................................48
Developmental and Reproductive Toxicity..............................................59
Immunotoxicity.........................................................................................62
Neurotoxicity............................................................................................63
Hematotoxicity.........................................................................................65
Vascular Disease.......................................................................................67
Diabetes Mellitus......................................................................................70
Respiratory Disease..................................................................................72
Biochemical and Cellular Toxicity...........................................................74
Skin Effects...............................................................................................75
Overview of Noncancer Epidemiology....................................................78
Carcinogenicity.........................................................................................79
Vulnerability of Infants and Children.....................................................115
DOSE-RESPONSE ASSESSMENT......................................................................116
Noncarcinogenic Effects...............................................................................116
Mode of Action.......................................................................................116
Animal Studies........................................................................................117
Human Studies........................................................................................118
Carcinogenic Effects.....................................................................................127
Mode of Action.......................................................................................127
Quantitation of Cancer Risks..................................................................141
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CALCULATION OF PROPOSED PHG.............................................................164
Non-Cancer Effects......................................................................................164
Cancer Effects...............................................................................................168
Lung and Bladder Cancer.......................................................................168
RISK CHARACTERIZATION............................................................................169
Non-Cancer Effects......................................................................................169
Cancer Effects...............................................................................................170
Sources of Uncertainty in the Quantitative Risk Estimates....................170
SUMMARY AND COMPARISON OF RECENT RISK ASSESSMENTS......181
OTHER REGULATORY STANDARDS.............................................................183
REFERENCES.......................................................................................................184

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PUBLIC HEALTH GOAL FOR ARSENIC
IN DRINKING WATER
SUMMARY
A causal association between human arsenic exposure, usually in the form of inorganic
compounds containing trivalent arsenite (As III) or pentavalent arsenate (As V), and
various forms of human cancer has been established for many years. The International
Agency for Research on Cancer (IARC) evaluated arsenic in 1980 and classified "arsenic
and arsenic compounds" in Group 1, which includes "chemicals and groups of chemicals,
which are causally associated with cancer in humans." Arsenic is also known to be
atherogenic, genotoxic, teratogenic, and may cause other adverse developmental effects
in exposed children.
Quantitative risk assessments of arsenic from inhalation exposures include the
U.S. Environmental Protection Agency (EPA) Health Assessment Document for
Inorganic Arsenic (U.S. EPA, 1984), and the California Department of Health Services’
Health Effects of Inorganic Arsenic Compounds (CDHS, 1990). OEHHA’s Arsenic
Recommended Public Health Level for Drinking Water Draft (OEHHA, 1992a) provided
a quantitative risk assessment for arsenic in drinking water. The Special Report on
Ingested Inorganic Arsenic: Skin Cancer; Nutritional Essentiality (U.S. EPA, 1988) also
provided a quantitative risk assessment applicable to drinking water exposure. Recently
the National Research Council’s Subcommittee on Arsenic in Drinking Water also
conducted evaluations and quantitative risk assessments deriving theoretical lifetime
excess risk estimates up to 23 in 10,000 for bladder cancer in males and up to 18 in
10,000 for lung cancer in males at 10 ppb arsenic (NRC, 1999, 2001). The U.S. EPA’s
final rule on arsenic in drinking water (U.S. EPA, 2001) developed an MCLG of zero.
The MCLG is the functional equivalent of the California public health goal (PHG) for
drinking water. The U.S. EPA also established a national primary drinking water
regulation or MCL for arsenic of 10 ppb. U.S. EPA’s upper bound (90th percentile)
estimates of lifetime cancer risk at 10 ppb ranged up to 6.1 in 10,000. This federal
regulation does not become fully effective until 2006. In California the MCL for arsenic
will be determined by the Department of Health Services to be as close to the PHG as
possible considering other factors such as cost and analytical feasibility. All of these
assessments recognize the relatively high cancer risks associated with chronic exposure
to inorganic arsenic. The current assessment refines and extends our earlier arsenic risk
assessment (OEHHA, 1992a).
OEHHA has developed a public health goal (PHG) of 0.004 µg/L (4 ppt) for arsenic in
drinking water based on the mortality of arsenic-induced lung and urinary bladder
cancers observed in epidemiological studies of populations in Taiwan, Chile, and
Argentina. For lung and bladder tumors combined, and both sexes combined, the
estimated unit risk was 2.7x10-4 (µg/L)-1. Similar unit risks were derived from a mouse
bioassay using prenatal exposure to arsenic. The risk estimates were based on a low-dose
linear extrapolation approach although the mode of carcinogenic action is not fully
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understood. The actual risks of low-level exposure are unlikely to exceed these risk
estimates but could be lower or zero. It should be noted that at low water concentrations
of arsenic food-borne arsenic would become the dominant source (Yost et al., 1998).
A noncancer health protective value of 0.9 µg/L (0.9 ppb) was developed based on
vascular effects in a human epidemiological study of cerebrovascular disease (Chiou
et al., 1997b). A benchmark dose approach was used to derive this value, with an
uncertainty factor of 10 for inter-individual variation and three for extrapolation from the
lower bound on the effect levels (LEDs) to negligible effect levels.1
INTRODUCTION
Arsenic is a naturally occurring element in the earth's crust and is very widely distributed
in the environment. All humans are exposed to microgram quantities of arsenic
(inorganic and organic) largely from food (25 to 50 µg/day) and to a lesser degree from
drinking water and air. Some edible seafood may contain higher concentrations of
arsenic which is predominantly in less acutely toxic organic forms.
In certain geographical areas, natural mineral deposits may contain large quantities of
arsenic and this may result in higher levels of arsenic in water. Waste chemical disposal
sites may also be a source of arsenic contamination of water supplies. The main
commercial use of arsenic in the U.S. is in pesticides, mostly herbicides and in wood
preservatives. Misapplication or accidental spills of these materials could result in
contamination of nearby water supplies. Burning of fossil fuels also produces low levels
of arsenic emissions. Arsenic may also be found in low levels in tobacco smoke.
Most ingested arsenic is quickly absorbed through the gastrointestinal tract into the blood
stream. Most of the organic arsenic (e.g., arsenobetaine) is excreted unchanged or
metabolized (e.g., arsenocholine → arsenobetaine). The inorganic arsenic which is
absorbed is converted by the liver to methylated forms which may be more toxic (i.e.,
trivalent MMAIII and DMAIII) and more efficiently excreted in the urine (e.g, DMA).
Arsenic does not have a tendency to accumulate in the body at low environmental
exposure levels.
In humans, while ingestion of larger doses of arsenic may be lethal, lower levels of
exposure may cause a variety of systemic effects including irritation of the digestive tract,

1 This document is based in part on an assessment conducted by Smith and Lopipero
(2001) under an interagency agreement between OEHHA and the University of
California. It represents an updating of our earlier draft “Arsenic Recommended Public
Health Level” (OEHHA, 1992a), which in turn was based on information in the report
"Health Risk Assessment for Arsenic Ingestion" prepared by A.H. Smith et al. (1990)
under contract to the California Department of Health Services. Additional details can be
found in these earlier documents. Common abbreviations used in this document: As,
arsenic, form unspecified; AsV, arsenate; AsIII, arsenite; MMAV, monomethylarsinic acid;
MMAIII, monomethylarsonic acid; DMAV, dimethylarsinic acid; DMAIII, dimethylarsonic
acid; Asi, inorganic arsenic oxidation state unspecified; MMA, monomethylarsenic
oxidation state unspecified; DMA, dimethylarsenic oxidation state unspecified.
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