Arsenic in Drinking Water 2001 Update (2001) / Chapter Skim
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4 Variability and Uncertainty
4 Variability and Uncertainty
Pages 133-168
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From page 133... ...
Given sufficient evidence, they combine data from multiple studies in the same species and from epidemiological and animal studies to estimate the health risks. These risks are estimated in the dose range for which observations have been made and are then extrapolated from these dose ranges to Tower doses that might be of concern for regulation.
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From page 134... ...
. VARIABILITY AND UNCERTAINTIES DISCUSSED IN TTIE 1999 REPORT In its discussion of variability in an arsenic risk assessment, the 1999 Subcommittee on Arsenic in Drinking Water concluded that characteristics of different individuals could contribute to variability in risk estimates.
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From page 135... ...
In addition, different foods contain varying concentrations of arsenic (IOM 2001~; therefore, an individuals food preferences will affect arsenic intake. Although this update focuses on risk from exposure to arsenic in drinking water, other factors that affect arsenic exposure from all sources are important to consider when interpreting the dose-response modeling based on use of available epidemiological data.
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From page 137... ...
The data clearly show vanability in water consumption with age, with the highest daily total water ingestion rates per unit of body weight occurring in infants and young children. In its risk assessment, EPA took the reported ingestion rates (given in milliliters per day)
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From page 138... ...
Water Consumption in the Taiwanese Study Population In its earlier risk assessment, EPA (1988) did not consider variability in water consumption per unit of body weight in the study populations when interpreting the epidemiological data on arsenic carcinogenicity in Taiwan or
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From page 139... ...
(b) So% ~ 70% 50% 40% 30% 20% 10% 0% 100% / Ad/ Of/ 0.5 - 0.9 4-6 7-10 - - - -11 -14 All ages 0 50 100 150 200 250 Water consumed, mL/kg/day 80% Anon /,7 - 15-19 - - 20 - 24 - 25-54 —55 - 64 —~ 65~ All ages 0 50 100 150 200 Water consumed, mL/kg/day 250 FIGURE 4-1 Cumulative distributions of water intake data by age.
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From page 140... ...
to account for variability in quantity of water consumed by the United States population without simultaneously accounting for variability in water consumption among the Taiwanese would have the result of underestimating the upper bound of risk attributable to arsenic in drinking water in the quantitative risk assessment. It is reasonable to assume that the Taiwanese had a variable intake of water as well, and biostatistical analysis should consider that the southwestern Taiwanese cohort consisted of a signif~cant proportion of males and females whose direct water consumption was less than 3.5 and 2.0 L/day, respectively.
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From page 141... ...
Although these data might support the hypothesis that children are at higher risk to the effects of arsenic in drinking water, the impact of the increased exposure in infants and young children on the risk assessment depends on what pattern of exposure correlates with the effect and whether the increased exposure is intrinsically accounted for in the design of the epidemiological studies used in the risk assessment. Those issues are discussed further in the section Dose Metrics and Model Uncertainty.
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From page 142... ...
Previous studies indicate that young individuals might have a lower rate of methylation of inorganic arsenic than adults (NRC 1999~. More recently, indigenous Andean children have been found to have about 45% oftheir urinary arsenic as dimethylarsinic acid (DMA)
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From page 143... ...
Because methylated forms of arsenic are readily excreted in urine, evaluation of arsenic methylation efficiency is generally based on the relative amounts of the different metabolites detected in urine (Vahter ~ 999a)
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From page 144... ...
In people living in northeastern Taiwan, where arsenic concentrations in drinking water might reach 3,000 ,ug/L, 27% of urinary arsenic was MMA (Chiou et al. ~ 997~; inorganic arsenic constituted only ~ 2% oftotal urinary arsenic metabolites.
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From page 145... ...
A few studies published to date on MA and DMA~ indicate variations in the excretion of these arsenic metabolites in urine. People exposed to arsenic in drinking water in Romania at 28-161 ,ug/L were found to excrete MA at 5-7 ,ug/L, on average, independent of the exposure concentration; in those individuals with very low exposures (2.8 ~Lg/L)
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From page 146... ...
. 70 80 90 100 50 60 70 80 90 100 FIGURE 4-2 Population variations in the percentage of urinary as various arsenic metabolites.
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From page 147... ...
The distribution pattern for the arsenic metabolites in the urine of individual Argentinian women exposed to arsenic in drinking water was remarkably stable over a period of about a week, indicating that an individual's methylation of inorganic arsenic is fairly constant over time (Concha 20014. Therefore, interindividual variation cannot be explained by the fact that in most studies there is only one urine sample per person.
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From page 148... ...
1999~. In a few children with some of the highest exposures, only 40-50% of urinary arsenic was DMA, MMA constituted 20%, and inorganic arsenic 25% of total urinary arsenic.
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From page 149... ...
Mexican people with signs of dermal toxicity due to exposure to arsenic in drinking water had a higher percentage of urinary arsenic MMA and a Tower percentage of DMA than those without visible dermal toxicity (Del Razo et al.
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From page 150... ...
SOURCES OF UNCERTAINTY Dose Metrics and Model Uncertainty The association between arsenic exposure and an adverse health effect can be calculated by comparing the response to a range of different dose metrics, including cumulative arsenic dose, average daily intake over a lifetime, and peak arsenic exposure, and using a wide range of different statistical models. The dose metric and model used can affect the calculation of risk estimates, and depending on how accurately exposure is measured by the dose metric, and how closely the metric is related to the end point of concern, more or less uncertainty is introduced to a risk assessment.
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From page 151... ...
However, if cumulative dose is important, or if arsenic acts as a late-stage carcinogen, information about the timing and amount of exposure is needed. At this time, the mode of action of arsenic and the dose metrics that are best correlated with the carcinogenic effects of exposure to arsenic in drinking water are not known.
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From page 152... ...
Ofthe estimated total arsenic intakes for infants, 42% originated from seafood and 31% from rice and rice cereals. Ofthe estimated total arsenic intakes, seafood contributed 76% to 90% for children (2-10 years old)
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From page 153... ...
Consistent with earlier studies, total arsenic concentrations (all concentrations reported as elemental arsenic per tissue wet weight) were highest in seafood (ranging from 160 ng/g in freshwater fish to 2,360 ng/g in saltwater fish)
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From page 154... ...
population. This hypothesis is based in part on the fact that cancer has been consistently associated with aspects of diet; both increased and decreased cancer risks have been associated with different dietary parameters (Doll and Peto ~ 981; N~C ~ 982; Steinmetz and Potter l99la,b; World Cancer Research Fund Panel 1997~.
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From page 155... ...
In a recent study from West Bengal, India (see Dermal Effects in Chapter 2) , it was demonstrated that among people exposed to high concentrations of arsenic in drinking water, those who were below 80% of standard body weight had a 1.6-fold increase in the prevalence of keratosis (Mazumder et al.
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From page 156... ...
Taken together, those data indicate that nutritional status might influence the risk for health effects following arsenic exposure. Thus, the risk estimates based on the population in southwestern Taiwan might have been influenced by the poor nutrition of that population at the time of the increased arsenic exposures.
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From page 157... ...
2000~. Second, although human diets vary substantially, patterns of cancer risk and protection against cancer are also relatively consistent across populations (WorId Cancer Research Fund Panel 1997~.
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From page 158... ...
(1995) examined the relationship between arsenic exposure in drinking water and bladder cancer and found a positive association between arsenic and bladder cancer only among smokers.
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From page 159... ...
~ 10~. Although the decision to implement a value-of-information approach reflects a policy choice, it might help to focus research efforts on those key uncertainties that would have the largest impact on our understanding of the magnitude of arsenic risks.
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From page 160... ...
· Geographical and cultural differences in arsenic exposures make it difficult to relate consumption habits in Taiwan with those in the United States. To make better comparisons and account for differences, more information is needed on arsenic content in foods, water-ingestion rates, foodpreparation practices, and nutritional status of the populations.
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From page 161... ...
· In considering how variability in the amount of drinking water consumed would affect quantitative risk assessment for arsenic, EPA should adjust for variability in consumption in the population that was the source of the data (e.g., the southwestern Taiwanese) , as well as in the general U.S.
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From page 162... ...
Clarification of the mechanisms of action of arsenic and development of an appropriate animal model for studying the effects of arsenic. Such clarification and development would help to reduce the uncertainty about dose metrics and the relevance of animal data for human risk assessments.
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From page 163... ...
1995. Case-control study of bladder cancer and arsenic in drinking water.
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From page 164... ...
2000. Lung cancer and arsenic concentrations in drinking water in Chile.
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From page 165... ...
1998. Arsenic levels in drinking water and the prevalence of skin lesions in West Bengal, India.
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From page 166... ...
1998. Marked increase in bladder and lung cancer mortality in a region of Northern Chile due to arsenic in drinking water.
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From page 167... ...
1979. Arsenic levels in human blood, urine, and hair in response to exposure via drinking water.
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From page 168... ...
2000. Arsenic methylation capacity and skin cancer.
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