Arsenic in Drinking Water 2001 Update (2001) / Chapter Skim
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2 Human Health Effects
2 Human Health Effects
Pages 24-74
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From page 24... ...
Specific dermal effects are characteristic of chronic arsenic exposure. Diffuse or spotted hyperpigmentation has been seen after 6 months to 3 years by chronic ingestion of high doses of arsenic (0.04 mg/kg/day, or 40 ~g/kg/day)
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From page 25... ...
On the basis of data from several epidemiological studies, particularly those examining exposed populations in Taiwan, Argentina, and Chile, the Subcommittee on Arsenic in Drinking Water concluded that the "evidence is now sufficient to include bladder and lung cancer among the cancers that can be caused by ingestion of inorganic arsenic" (NE2C 1999~. The subcommittee further concluded that although some evidence indicated an increased risk of cancers other than skin, lung, and bladder, the database was not as strong, and confirmatory studies would be needed to establish arsenic as an underlying cause in other cancers.
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From page 26... ...
who resided their entire lives in one of four villages in a rural area of Bangladesh. Many villages in Bangladesh have high arsenic exposures resulting from the use of groundwater for drinking water; wells were drilled because of microbial contamination of surface waters.
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From page 27... ...
The authors concluded that the HWSE might have contributed to the apparent lack of arsenic-associated cardiovascular disease mortality in prior occupational cohort studies, in contrast to positive effects observed in several drinking-water studies. Dermal Effects Chronic arsenic exposure causes a characteristic pattern of noncancer dennal effects that begins with spotted hyperpigmentation and might later include palmer and planter hyperkeratosis.
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From page 28... ...
(l 998) conducted a cross-sectional survey of the prevalence of truncal hyperpigmentation and palmar-plantar keratosis in a region of West Bengal, India, with groundwater arsenic concentrations ranging from nondetectable to 3,400 ,ug/~.
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From page 29... ...
The age-adjusted prevalence of any arsenic-related skin lesion increased in relation to the arsenic concentration ofthe drinking water. In mates in the lowest exposure category (drinkingwater arsenic, < ~ 50 ~g/~)
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From page 30... ...
A small number of epidemiological studies investigating the relationship between arsenic exposure in humans and adverse reproductive effects have been published since the 1999 report, but they suffer from some limitations and are not necessarily applicable in populations exposed to arsenic in drinking water. A hospital case-control study found an increase of stillbirths in relation to the proximity of maternal residence to an arsenical pesticide production plans in Texas (]
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From page 31... ...
This study was based on recall of previous pregnancies, however, and ascertainment of the outcomes was not clearly defined. In summary, although several studies have addressed the potential reproductive effects of arsenic exposures in humans, the evidence is not conclusive.
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From page 32... ...
Although subjects lived in areas that apparently had different environmental arsenic concentrations, it was not stated whether the examiners were blinded to the location of residence. In addition, no data were presented regarding the concentration of arsenic in the children's drinking water, the concentration in the subjects' urine, or the presence of arsenic-related skin lesions in any subject.
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From page 33... ...
Examiners were not blinded to the presence of arsenic-related skin lesions. However, the large size of the study, the high odds ratios observed, and the positive trend with current arsenic exposure were such that the study provides support for reports of arsenic-associated pulmonary effects previously noted in Chile in the 1 960s and ~ 970s (see NRC ~ 999~.
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From page 34... ...
and albumin were normal and did not differ significantly between the groups. Twenty-six percent of the subjects from the middle- and high-exposure towns were reported to have at least one skin lesion associated with arsenic exposure.
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From page 35... ...
It is not clear whether differences in the intensity and temporal pattern of arsenic dose contributed to the disparate findings in those studies. Diabetes The main focus of research looking at the effects of arsenic on the endocrine system is the association between arsenic exposure and diabetes mellitus.
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From page 36... ...
I-~ .37~. Because only mortality attributed primarily to diabetes mellitus was examined, studies such as this one might underestimate an association between arsenic exposure and the population risk of the disease.
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From page 37... ...
was calculated as the product of the median arsenic concentration of the well water in every village that a subject inhabited at some point in his or her life multiplied by the length of time they consumed well water in that village. Individuals were excluded if complete arsenic exposure data were not available.
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From page 38... ...
General Issues with Exposure Measurement In reviewing relevant data developed on measuring arsenic exposure since the 1999 NRC report Arsenic and Drirlking Water, it is worthwhile to begin by considering concepts of exposure and dose, because numerous definitions and methods of estimating exposure have been developed. Exposure and dose are related but separate concepts.
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From page 39... ...
39 · A' o A, au · v)
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From page 40... ...
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From page 41... ...
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From page 42... ...
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From page 43... ...
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From page 44... ...
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From page 45... ...
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From page 47... ...
No biomarkers of arsenic exposure were used. The interview included information on history of well-water consumption, residential history, sociodemographic characteristics, cigarette smoking, personal and family medical history, occupation, and other potential risk factors.
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From page 48... ...
Cox's proportional hazards regression analysis (adjusted for sex, age, and cigarette smoking) was conducted to estimate relative risks and 95°/O confidence intervals by concentration and duration of arsenic exposure.
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From page 49... ...
, more than one well had been used in their houses, and their past arsenic exposure data were derived from their current well data (Cantor 2001~. Those 2,1 19 subjects had used their current well for approximately 60% of their life spans (standard deviation = 21 years)
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From page 50... ...
In an effort to avoid overmatching by geographic area, and thus relative concentrations of arsenic in drinking water, the authors sought to select controls from the study hospitals in a manner that would reflect the distribution of arsenic exposure in the overall population from which the cases arose. To do that, the probability of selecting a control from each ofthe Bight hospitals was based on the relative frequency of adm~ssion to that institution in 1991.
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From page 51... ...
The expected impact of the overselection in the highest-exposure category is to diminish estimates of risk, and underselection in the Tower stratum is to enhance risk estimates. As the authors noted, this assessment is indirect, because in the data analysis the actual historical residential location of cases and controls rather than their location at the time of the study was used to determine arsenic exposure levels.
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From page 52... ...
Strengths of this study include an acceptable response rate, unbiased ascertainment of exposure, individual estimates of exposure, exposure coverage of most of the life span for most study subjects, incorporation of individual data on other potentially confounding risk factors for lung cancer, appropriate analyses of study data, and an adequate study size. This is the only study available for risk assessment that has individual estimates of exposure on all subjects for more than 40 years, well beyond the minimum latency for lung cancer.
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From page 53... ...
by the number of years of exposure to yield an exposure with units of parts per billion-years, arranged into three groups: |
From page 54... ...
Presumably, exposure that occurred during periods when a person did not live in one of the study communities was not included in the estimate of exposure used in the analysis, creating the possibility that cumulative lifetime arsenic exposure might have been incompletely ascertained for some of the cohort. The range of arsenic concentrations reported in Lewis et al.
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From page 55... ...
(1999a) study identified a total of 34 respiratory cancers, of which 30 were lung cancers, and a total of five bladder cancers.
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From page 56... ...
In particular, it has been argued that differences in general nutritional status or selenium intake between the relatively poor farming and fishing communities of southwestern Taiwan (the locate of high arsenic exposures from water and the studies used for the EPA risk assessment) and the remainder of the country were great enough to result in increases of risk that might erroneously be attributed to drinking-water arsenic exposures.
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From page 57... ...
It is possible that the relatively high arsenic exposure of the study population and the large size of the study in terms of person-years of observation might have enabled these statistically significant increases to emerge. Kurttio et al.
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From page 58... ...
Among the shorter latency group, smokers with average arsenic concentrations of 0.5 ~g/L or above had a relative risk of ~ 0.3 (95% CT = ~ . ~ 6-92.6~; the relative risk among nonsmokers in this arsenic exposure group was 0.87 (95% CT = 0.25-3.02~.
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From page 59... ...
Among subjects with toenail arsenic concentrations above the 97th percentile, the adjusted odds ratios were 2.07 (95% CT = 0.92-4.66)
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From page 60... ...
Two exposure metrics were used in the data analysis: peak arsenic concentration (PAC) , defined as the highest well-water arsenic concentration reported by an individual, and cumulative arsenic dosage (CAD)
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From page 61... ...
That period between the critical exposure to the carcinogenic agent and the occurrence of the cancer is referred to as the latency period. Latency is usually estimated by determining the period between the time of first exposure to the carcinogen and the clinical detection of the cancer, and studies have been conducted that provide information on the latency period of arsenicinduced skin cancer and internal cancers.
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From page 62... ...
(1998) studied 17 patients in Singapore with skin lesions who had taken Chinese medicines containing arsenic and estimated a mean latency period for Bowen's disease of 39 years (range of 29-50 years)
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From page 63... ...
In addition, many years usually elapse between the clinical diagnosis of skin cancer and mortality from skin cancer, implying a shorter latency for occurrence of those cancers. ~ the case of internal cancers, the data are from epidemiological studies; however, few of those studies address latency (see Table 2-3~.
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From page 64... ...
Using a time-window analysis of bladder cancer case-control data and arsenic exposure from the state of Utah, Bates et al.
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From page 65... ...
2000) in the arsenic endemic area of southwestern Taiwan found a positive association with cumulative arsenic exposure that was generally consistent with the prevalence study by Rahman et al.
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From page 66... ...
Findings from a large prevalence study in West Bengal, a small prevalence study in Bangladesh, and an ecological mortality study in the area of southwestern Taiwan where arsenic is endemic add to previous suggestions that arsenic ingestion might be associated with noncancer respiratory effects. The pathology that characterizes these effects has not been defined.
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From page 67... ...
They incorporated individualized information on long-term arsenic exposure and health outcome. They also gathered and analyzed information on other risk factors, such as smoking habits, from individuals.
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From page 68... ...
From a public-health perspective, the database of epidemiological studies linking arsenic in drinking water with increased risk of skin, bladder, and lung cancer provides a sound and adequate basis for quantitative assessment of cancerrisk. RECOMMENDATIONS Epidemiological studies are highly recommended to investigate the dose-response relationship between arsenic ingestion and the noncancer end points of circulatory system disease (particularly hypertension, cardiovascular disease, and cerebrovascular disease)
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From page 69... ...
· Epidemiological studies should be designed to be of sufficient size to determine risk in subpopulations that might be susceptible to the adverse effects of arsenic and to quantify the extent of interaction with host factors. · Data from additional follow-up of exposed populations, including populations in Utah, Chile, Bangladesh and West Bengal, should be considered, as appropriate, in future risk assessments.
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From page 70... ...
Tail 1995. Increased prevalence of hypertension and long-term arsenic exposure.
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From page 71... ...
Smith.2000. Lung cancer and arsenic concentrations in Mung water in Chile.
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From page 72... ...
2000. Measurement of low levels of arsenic exposure: a comparison of water and toenail concentrations.
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From page 73... ...
1998. Marked increase in bladder and lung cancer mortality in a region of northern Chile due to arsenic in Winking water.
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From page 74... ...
1998. Cutaneous manifestations of chronic arsenicism: review of seventeen cases.
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