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OCR for page 118
Ill
Epidemiology of the
Adverse Health
Effects of Arsenic and
Asbestos in Drinking Water
Both arsenic and asbestos were reviewed in earlier volumes of the Drinking
Water arid Health series. The discussions in this chapter are limited
primarily to important new epidemiological data that became available
after Volumes 1 and 3 had been completed and to reassessments of some
older studies of effects of arsenic and asbestos in human populations.
ARSENIC
Arsenic was evaluated in the first and third volumes of Drinking Water
and Health (National Research Council, 1977a, pp. 316-344; 1980, pp.
337-345~. It was also comprehensively evaluated in 1977 by another com-
mittee (National Research Council, 1977b). Epidemiological studies re-
viewed in those volumes have provided conflicting associations between the
presence of arsenic in drinking water and the development of skin cancer.
Some studies discussed below were reviewed in previous volumes, while
several were published after the previous volumes were prepared. One of
the new reports evaluated by the committee is a review of the carcinogenic-
ity data on arsenic, which was prepared by the International Agency for
Research on Cancer (1980~. That agency concluded that, although there is
inadequate evidence for the carcinogenicity of arsenic compounds in ani-
mals, there is "sufficient evidence that inorganic arsenic compounds are
skin and lung carcinogens in humans." This statement presumably applies
to all sources of arsenic, including drinking water. It is based on the conflict-
OCR for page 119
Adverse Health Effects of Arsenic and Asbestos 119
ing results from only two epidemiological studies (Morton et al., 1976;
Tseng, 1977; Tseng et al., 1968~.
The adverse health effects of exposure to arsenic compounds have been
examined in epidemiological investigations for nearly a century. Investiga-
tors have gathered and examined data from a variety of sources, including
patients given prescribed medicinal arsenic compounds, several occupa-
tionally exposed groups, and populations exposed to high levels of arsenic
in drinking water supplies (Arguello et al., 1939~. Although arsenic expo-
sure has been associated primarily with skin cancer, associations with
other cancers, cardiovascular dysfunctions, and a peripheral vascular dis-
order known as "blackfoot" disease have also been found.
Epidemiological investigations in Europe (Geyer, 1898), in several
South American countries, e.g., Argentina (Arguello et al., 1939) and
Chile (Borgono et al., 1977; Zaldivar, 1974), and in Taiwan (Tseng, 1977;
Tseng et al., 1968) have suggested an association between the effects of
chronic exposure to high levels of arsenic in drinking water and the occur-
rence of a variety of skin disorders, including skin cancer. The most signif-
icant of these reports was published by Tseng and colleagues, who not only
correlated a high prevalence of skin cancer and blackfoot disease with the
arsenic contents of drinking water supplies in Taiwan but also reported a
dose-response relationship between both skin cancer and blackfoot disease
and the duration of water intake based on a detailed house-to-house medi-
cal survey of approximately 40,000 people out of a total exposed popula-
tion of about 100,000 individuals (Tseng, 1977; Tseng et al., 1968~. The
inhabitants of the area with endemic arsenic exposure began using arte-
sian wells with high arsenic levels approximately 45 years before the study
by Tseng et al. (1968~. Most of these people were engaged in farming, fish-
ing, or salt production, and their socioeconomic status was considered to
be poor. Their diet was low in animal protein and fat, but high in carbohy-
drates. Their habits and customs were not considered different from those
of persons living in other parts of Taiwan. The overall prevalence rates for
skin cancer, hyperpigmentation, and keratosis were 10.6, 183.5, and 71.0
per 1,000, respectively. The skin cancers observed were atypical, in that
approximately three-quarters of them were located on parts of the body not
usually exposed to sunlight and more than 99~o of the patients had more
than one lesion.
The control population consisted of 7,500 persons living in a low arsenic
exposure area, where drinking water concentrations of the element ranged
from less than 1 ppb (~g/liter) up to 17 ppb. Approximately two-thirds
~—5,000) of the controls lived on the nearby island of Matsu. Most of them
were fisherman. The remainder of the controls, who lived in villages near
the endemic exposure area, were farmers and salt workers. The sex and
OCR for page 120
120 DRINKING WATER AND HEALTH
age distribution in the control group was similar to that in the exposed
group. Not a single case of melanosis, keratosis, or skin cancer was ob-
served in the control population.
More than 45~0 of the wells seeing as drinking water supplies for the
"exposed inhabitants" had arsenic levels in excess of 400 ppb, compared
with the U.S. Environmental Protection Agency (EPA) national drinking
water standard of 0.05 mg/liter (50 ppb) (U.S. Environmental Protection
Agency, 1976~. In attempts to establish a dose-response relationship, in-
vestigators compared three groups, based on drinking water levels of arse-
nic: ~ 300 ppb, 300 to 600 ppb, and ~ 600 ppb. There was a definite as-
cending gradient or prevalence of effects from the low to high arsenic
groups for both sexes in three different age groups, but no calculations of
statistical significance across exposed groups were presented.
In three epidemiological studies conducted in the United States, investi-
gators found no positive relationship between high levels of arsenic in
drinking water and adverse health effects. More than 200 residents of Fair-
banks, Alaska, exposed to drinking water containing mean arsenic levels
of 224 ppb displayed no increases in skin disorders, although the longest
exposure in the study population was only 10 years (Harrington et al.,
1978~. Similarly, Morton et al. (1976) did not note any increase in the inci-
dence of skin cancer between 1958 and 1971 in Lane County, Oregon,
where the arsenic content of the drinking water supplies was relatively
high; however, only 537O of the arsenic levels of those supplies exceeded 100
ppb. In a recent study in Utah, Southwick et al. (1981) compared the
health status of 145 people consuming drinking water containing arsenic
levels of approximately 200 ppb and a matched control group of 105 par-
ticipants from a neighboring community, where drinking water levels of
arsenic averaged 20 ppb. The investigators did not find any cutaneous
manifestations of arsenic toxicity. In addition, there was no excess of can-
cer incidence and death rates in the exposed community.
There are several possible explanations for the apparently conflicting
results discussed above. One is the striking difference in the arsenic levels
of the drinking water supplies surveyed; the average arsenic content of the
supplies in Taiwan greatly exceeds those of the U.S. communities studied.
Moreover, the duration of exposure was probably shorter and the amount
of arsenic ingested much less in the U.S. studies than in the Taiwan stud-
ies, where personal mobility is greatly limited. Furthermore, lack of ade-
quate nutrition and exposure to other environmental pollutants may have
exacerbated the effects of arsenic exposure in Taiwan. The differences in
exposure to sunlight between Taiwan and Alaska may have been a factor in
the observed absence of skin disorders in the Fairbanks study (Harrington
OCR for page 121
Adverse Health Effects of Arsenic are Asbestos 121
e! al., 1978) and the Utah study (Southwick et al., 1981~. None of the in-
vestigators attempted to determine which arsenic compounds were present
in the drinking water supplies surveyed. Since arsenic toxicity varies from
compound to compound, this may have been a factor in the conflicting
results of the different studies.
Unfortunately, the Taiwan studies did not include analyses of drinking
water constituents other than arsenic in the water sources of the exposed
and control groups. This lack of assessment reduces the extent to which
confidence can be placed in the postulated association between arsenic lev-
els and observed skin cancer. This is particularly relevant since Lu (1978)
recently reported the presence of ergot alkaloids in the Taiwan well water
associated with blackfoot disease. These alkaloids may cause symptoms
similar to those of blackfoot disease. Other aspects of the Taiwan study
might also be questioned. For example, there is a possibility that the ob-
servers might have been biased by knowledge of the high- or low-exposure
areas. Moreover, only about 30% of the skin cancers were verified by bi-
opsy. The extent to which these factors may affect the interpretation of the
findings is uncertain.
The assessment of arsenic for adverse health effects is confounded by
several issues. First, it is always of great value when epidemiological associ-
ations are supported with animal studies; however, animal studies have
generally not indicated that arsenic is carcinogenic (International Agency
for Research on Cancer, 1980; U.S. Environmental Protection Agency,
1979~. Second, arsenic is now recognized as an essential nutrient in several
mammalian species (e.g., the rat, chick, guinea pig, and goat) and possi-
bly in humans as well Extrapolation from data on animals suggests that
25 to 50 fig of arsenic per person may be the daily requirement for humans
(U.S. Environmental Protection Agency, 1979~.
When deriving the current maximum contaminant level (MCL) for arse-
nic, the EPA took into account the consumption of arsenic in food as well
as its association with skin cancer in the Taiwan study (U.S. Environmen-
tal Protection Agency, 1976~. Using data from Schroeder and Balassa
(1966), the agency estimated that humans consumed approximately 900 fig
of arsenic daily from food. The SO ~g/liter MCL (0.05 mg/liter) for arsenic
in drinking water was based on the assumption that not more than loo of
the total ingested arsenic would be prodded by that source. After the in-
terim arsenic standard was established, the estimate of dietary arsenic con-
sumption was greatly reduced from 900 to approximately 70 Heyday (U.S.
Environmental Protection Agency, 1976, 1977, 1979~. Because the ration-
ale behind the drinking water standard (U.S. Environmental Protection
Agency, 1976) is to keep the arsenic exposure from drinking water at 105ro
OCR for page 122
122 DRINKING WATER AND HEALTH
of total ingested arsenic, the more recently recognized lower dietary expo-
sure may necessitate a reevaluation of the current drinking water stan-
dard.
An important related issue is that the EPA has decided that there is no
threshold dose for chemical carcinogens. Consequently, there is no safe
exposure level to a carcinogen. Various biostatistical models have been
used to predict the risk of cancer occurrence when human exposures are
much lower than those in the observable range for which dose-response
relationships are known. The EPA Carcinogen Assessment Group used a
modified "one-hit" model to apply this type of downward extrapolation to
the Taiwan data (U.S. Environmental Protection Agency, 1981~. The
results indicated that the lifetime risk of skin cancer from drinking water
containing 20 ppb (or approximately one-half of the federal standard)
would be 1 per 100. This prediction is at variance with the negative find-
ings in the U.S. epidemiological studies cited above. Although the negative
epidemiological studies on U.S. populations raise questions about the can-
cer risk estimations based on the Taiwan data, it is not possible to deter-
mine whether such discrepancies are caused by inadequacies of the Taiwan
studies, the specific risk assessment model used, or a combination of both.
CONCLUSIONS AND RECOMMENDATIONS
The epidemiological studies on U.S. populations have failed to confirm the
association between arsenic in drinking water and the incidence of cancer
observed in Taiwan. Furthermore, only 0.4~o of the drinking water sam-
ples taken from public water supplies in the United States have exceeded a
total arsenic concentration of 0.01 mg/liter (National Research Council,
1980~. This finding is in sharp contrast to the average concentration of 0.4
mg/liter (400 ppb) reported in the Taiwan studies. It is therefore the opin-
ion of this committee that 0.05 mg/liter provides a sufficient margin of
safety, but that further experimental research and epidemiological evalua-
tions of the association of elevated levels of arsenic in drinking water and
skin cancer be undertaken.
Continued study of those U.S. populations exposed to high levels of ar-
senic in their drinking water appear warranted. Efforts should also be di-
rected toward discovering the differences that exist between the chemical
species of arsenic in Taiwan and those in the United States or the presence
of any other potentially confounding factors. Moreover, the development
of an appropriate animal model for carcinogenicity studies would help to
resolve the equivocal epidemiological studies. In addition, there should be
investigations about interactions of arsenic and other environmental fac-
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Adverse Health Effects of Arsenic and Asbestos 123
tors that may account for the observed differences in clinical studies as well
as the effects of diet, race, and climate.
Research should also be designed to evaluate the possible essentiality of
arsenic for humans a requirement that has been demonstrated in four
mammalian species. In the absence of new data, the conclusion reached in
the third volume of Drinking Water and Health remains valid, i.e., "If
0.05 mg/kg of dietary [total] arsenic is also a nutritionally desirable levee
for people, then the adequate human diet should provide a daily intake of
approximately 25 to 50 fig. The current American diet does not meet this
presumed requirement" (National Research Council, 1980~. The unre-
solved status of this issue is further reason for maintaining the current
MCL for arsenic.
ASBESTOS
Asbestos fibers in drinking water and their putative health effects were
reviewed in the first volume of Drinking Water arid Health (National Re-
search Council, 1977, pp. 144-168~. At that time, there were only limited
data from which to evaluate the potential adverse health effects of orally
ingested asbestos. A number of research recommendations suggested in
that volume have been, to some extent, fulfilled. Advances have been made
in the detection, identification, and quantification of asbestos fibers in
drinking water. Several chronic feeding studies completed since that time
have failed to show an effect between the ingestion of various fiber types
and the development of cancer at any site.
There have also been a number of epidemiological studies in which the
exposure to asbestos in drinking water and the incidence of cancer at se-
lected sites have been investigated. This renew is limited to a discussion
and evaluation of those studies and the development of a model to predict
the risks, if any, from such exposure.
BACKGROUND
A marked increase in the incidence rates of lung cancer and both pleural
and peritoneal mesothelioma has been absented in workers exposed to as-
bestos through inhalation (International Agency for Research on Cancer,
1977~. An excess of gastrointestinal tract cancers has also been.found in
these occupationally exposed groups.
The general population may be exposed to asbestos fibers in "air, be`,er-
ages, drinking water, food and pha~..aceutical and dental preparations
and by consumer use of asbestos containing products" (International
Representative terms from entire chapter:
skin cancer
