- Email: [email protected]
Arsenic, cancer, and thoughtless policy
Ecotoxicology and Environmental Safety 55 (2003) 139–142
Commentary
Arsenic, cancer, and thoughtless policy Gary Kayajanian* 1600 South Joyce Street, Suite 1411, Arlington, VA 22202, USA Received 13 February 2002; accepted 7 March 2002
Abstract The current drinking water contaminant standard for arsenic is 50 mg/L, as an upper bound. There is no lower bound for the standard. In an analysis of three epidemiology studies, the author demonstrates a significant cancer incidence trough for arsenic near 50 mg/L. Allowing, and even requiring, a much lower arsenic standard is not a desirable health outcome. Since most water systems currently deliver arsenic at levels below 5 mg/L, an undesirable health outcome is expected. For these systems and others not near 50 mg/L, the level of arsenic should be adjusted to bring it near 50 mg/L. r 2003 Published by Elsevier Science (USA). Keywords: Arsenic; Cancer; Anticarcinogen; J-shaped exposure–response curve
1. Introduction The finding by scientists that arsenic is a human carcinogen at prolonged high exposures is a conclusion that is of little value to regulators, because it mispredicts and misreads the carcinogenic effects of arsenic at the low levels to which man is exposed. The author has examined three epidemiology data sets to support this argument, including the very study the EPA and the NRC have relied on to defend lowering the current arsenic maximum contaminant level from 50 mg/L in drinking water (National Research Council, 1999, 2001; US EPA, 2001).
2. Methodology On a graph in which human cancer mortality rate is plotted as a function of lifetime arsenic exposure level, imagine two data points—one that represents cancer mortality at a background arsenic exposure, and a second which reports a significantly elevated cancer mortality at a high arsenic exposure level. That highdose human cancer mortality elevation is sufficient to earn the designation ‘‘carcinogen’’ for arsenic. Such a designation is applied to arsenic without regard to *Corresponding author. E-mail address: [email protected] (G. Kayajanian).
exposure level, and carries with it the assumption that if one reduces exposure to arsenic, one also reduces cancer mortality over the full exposure range from high to background to zero. Whether the pattern of cancer reduction is linear, sublinear, exponential, or some combination, as exposure to arsenic decreases, cancer mortality must also decrease. Such is the foundation of current regulatory thinking. What if there is a third data point on the graph at a low arsenic level—between background and high exposures—where cancer mortality is significantly reduced from background mortality, thereby generating an exposure–response curve with a J shape. Because of the significant low-exposure reduction in cancer mortality, arsenic should be designated an ‘‘anti-carcinogen’’, which carries with it the assumption that as one reduces arsenic exposure from low through background to zero, cancer mortality increases. Such a low-exposure data point also negates the assumption, cited above, surrounding the high-dose cancer designation of arsenic. How does one distinguish between EPA’s traditional cancer classification of arsenic where cancer mortality always decreases as arsenic exposure decreases, and the J-shaped curve I have postulated for arsenic? It is accomplished by examining the cancer mortality associated with the low-exposure region of the graph, where the two models’ predictions are opposite. First, clarification is needed. The J-shaped curve I have described is defined by three data points. My
0147-6513/03/$ - see front matter r 2003 Published by Elsevier Science (USA). doi:10.1016/S0147-6513(02)00042-8
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G. Kayajanian / Ecotoxicology and Environmental Safety 55 (2003) 139–142
designation of these points (background, low, and high) is arbitrary and flows from my presentation of the model. If they represent the arsenic levels of an actual data set that the EPA Administrator relies on to set arsenic levels in drinking water, then she should increase the arsenic level to what corresponds to the cancer mortality trough. If the three points had different designations—say, below background, background, and high—where background corresponded to the trough, the Administrator should order no change in arsenic levels. And finally, if the three points were ‘‘further below background,’’ ‘‘below background,’’ and ‘‘high,’’ where the trough is associated with ‘‘below background,’’ she should lower the arsenic level to below background but not further. Therefore, if the J-shaped model describes the arsenic human mortality data, there is regulatory value in determining the arsenic exposure that corresponds to the cancer trough.
3. Analysis The first data set I examine is Table A10-1 of the 1999 NRC report cited above, on pp. 308 and 309. It is the Taiwan data set both EPA and the NRC relied on to draw conclusions about arsenic. That table reports the number of lung, liver, and bladder cancers in men and women in each of the 42 villages studied. Within each village these cancers are associated with a specific number of man- or woman-years of exposure. The 42 villages are rank-ordered from least to most arsenic in the drinking water, measured in units which are easily converted to micrograms per liter. Most of the villages had a single well source for water, and its arsenic level was used for the ranking. For those villages with an odd number of wells, the middle arsenic level was used to rank the village. For those villages with an even number of wells, the arithmetic mean of the middle two wells was used for ranking. For my analysis of cancer mortality in men, for arsenic exposure I grouped the villages by fives: the lowest five, the next lowest five, and so forth,y, generating nine exposure groups. For each exposure group I totaled the number of lung, liver, and bladder cancers (15 values for the first eight exposure groups) and put the sum in the numerator of a cancer measure. In the denominator I totaled the man-years associated with these cancers. For simplicity, I expressed the fraction as cancers/1000 man-years. These nine fractions are presented in Table 1. In the lowest exposure group of five villages, the number of cancers/1000 man-years is more than three times higher than in the next lowest group of five villages—a difference that is significant at Po0.001. The second lowest exposure group corresponds to the cancer mortality trough for the men.
The same process was used to analyze the cancer mortality data for the women, also presented in Table 1. In the lowest exposure group of five villages, the number of cancers/1000 woman-years is more than three times higher than in the second and third lowest exposure groups—a difference that is significant at Po0.001. The lowest exposure group included villages whose arsenic level ranged from 10 to 32 mg/L; the second group, from 42 to 60 mg/L; and the third from 65 to 110 mg/L. The EPA Administrator should establish a new arsenic standard with lower and upper bounds that correspond to the cancer mortality trough. How does this analysis differ from the Morales et al. (2000) treatment of the same data set that EPA relied on? They employed only four exposure groups, the lowest of which embraced the 13 villages with arsenic levels ranging from 0 to 100 mg/L—the five villages from my lowest exposure group, the five from my second lowest exposure group, and the next three villages. Their grouping obscured the significant mortality pattern between my lowest two exposure groups, and thereby did not contradict the traditional EPA modeling of cancer mortality data. The Utah mortality data set I employed to test my observations from the Taiwan Study was graciously provided by EPA staff, who calculated mean lifetime arsenic exposure in units convertible to micrograms per liter for each of the 4055 men and women whose deaths—some by cancer—were reported. I employed four exposure groups to measure changes in cancer mortality incidence: 0 to o25; 25 to o75; 75 to o150; and 150–175 mg/L. I employed two cancer mortality measures: the six cancer classifications which were elevated in the Taiwan data—lung, liver, bladder, kidney, colon, and melanoma—per hundred deaths (Chen et al., 1985); and total cancers per hundred deaths (Table 2). For the men, either cancer measure is higher in the lowest exposure group than in the next lowest group, but not significantly. For the women, the six-cancer measure is more than fourfold higher in the lowest exposure group than in the next lowest, which is significant (Po0.001); the total cancer measure is more than threefold higher in the lowest exposure group than in the next lowest, which is also significant (Po0.000001). For the population as a single unit, i.e., men and women combined, the six-cancer measure is 90% greater in the lowest exposure group than in the next lowest (Po0.02). The total cancer measure is 65% higher in the lowest exposure grouping than in the next lowest (Po0.001). A third data set, from the 1982 Cuzick et al.’s article in the British Journal of Cancer, is structurally different than the Taiwan and Utah data sets. The pooled population of men and women were intentionally dosed with arsenic for medicinal purposes and standardized
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Table 1 Taiwan’s internal cancer (lung, liver, and bladder) mortality data Village group 1
Exposure range (mg/L)
Int. cancer deaths per 1000 man years
10–32
P value and direction between groups
1.65
Int. Cancer deaths per 1000 woman years 1.62
o0.001, down 2
42–60
0.53
3
65–110
0.76
4
110–256
1.13
5
259–398
1.29
6
406–520
2.18
7
520–599
1.95
8
650–698
2.43
9
717–934
1.48
P value and direction between groups o0.001, down
0.51 o0.20, up
o0.93, up 0.52
o0.12, up
o0.05, up 0.98
o0.63, up
o0.40, down 0.75
o0.03, up
o0.11, up 1.25
o0.56, down
o0.47, up 1.49
o0.22, up
o0.17, up 1.99
o0.04, down
o0.10, down 1.29
Note. From National Research Council (1999).
Table 2 Utah cancer mortality as a function of lifetime arsenic exposure: limited cancer grouping (lung, liver, bladder, kidney, colon, and melanoma) and total cancer in men and women Exposure range (mg/L)
Size of group
Men 0 to o25
932
Number of six cancer grouping
Cancers per 100 people
25
2.682
P Value, direction between groups
Number of total cancers
Cancers per 100 people
75
8.047
o0.39, down
P value, direction between groups
o0.58, down
25 to o75
554
11
1.986
40
7.220
75 to o150
273
5
1.832
31
11.355
150–175
334
15
4.491
40
11.976
Women 0 to o25
838
22
2.625
77
9.189
13
2.784
23 57
9.504 13.735
152
8.588
53
5.191
54
10.485
97
12.951
o0.08, up o0.07, up
o0.01, down
25 to o75
467
3
0.642
75 to o150 150–175
242 415
5 10
2.066 2.410
Men+women 0 to o25
1770
47
2.655
25 to o75
1021
14
1.371
75 to o150
515
10
1.942
150–175
745
25
3.338
o0.000001, down
o0.10, up
o0.01, up
o0.02, down
o0.001, down
o0.43, up
o0.001, up
o0.13, up
cancer mortality was presented as a function of two variables: increasing total dose and time in years since the first dose (Table 3, which borrows heavily from Cuzick’s Table 3.). In this study, I view the outside reference as the lowest exposure group, and the lowest
o0.21, up
dosed group as the next lowest exposure group. In all the time intervals (0–5, 6–10, 11–20, and beyond 20 years), the lowest dosed group (p500 mg) had fewer cancers than expected from the outside reference. Over all time intervals 10 cancers were observed in the lowest
G. Kayajanian / Ecotoxicology and Environmental Safety 55 (2003) 139–142
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Table 3 Observed (O) and expected (E) cancers by dose and time from first known treatment
Time (years) o5 5–9 10–19 X20 All years
Dose:o500 mg
500–999 mg
O
E
O
0 3 4 3 10
2.99 3.37 7.14 4.84 18.34
2 3 4 0 9
1000–1999 mg
X2000 mg
All levels
E
O
E
O
E
O
E
1.45 1.25 2.21 1.87 6.78
0 1 4 2 7
1.05 1.04 1.75 0.74 4.58
0 4 0 4 8
0.95 1.01 1.86 2.33 6.15
2 11 12 9 34
6.45 6.67 12.90 9.78 35.85
Note. From Cuzick et al. (1982).
dosed group, and 18.34 cancers were expected from the outside reference (Po0.06). At the higher dosings, 14.41 cancers were expected; 24 were observed. The most common dosing regimen in the Cuzick study was 250 mg/month, and the mean exposure time was about 9 months. Clearly, as a short-term exposure data set, Cuzick study is not equatable to Taiwan and Utah, and not helpful in establishing any exposure placement of a lifetime cancer mortality trough. Still, it establishes a J shape for the cancer mortality curve. The Cuzick data may be helpful in suggesting the effect of arsenic on cancer mortality. In the 5 years following initial arsenic medication, 6.45 cancer deaths were expected; in the second 5 years, 6.67—a total of 13.12 cancer deaths. And over those 10 years, 13 deaths were recorded: but only 2 occurred in the first 5 and 11 occurred in the second 5 years (Po0.02)—a timing which suggests that any cancers ‘‘promoted’’ in the second 5 years are entirely offset by those prevented in the first 5 years.
4. Discussion In the past a drinking water contaminant level has been set as an upper bound only. The preceding analysis of arsenic epidemiology data concludes that for this chemical both a lower and an upper bound limit are desirable, and these bounds span the current upper limit of 50 mg/L. If current arsenic contaminant levels were just below the current 50 mg/L, water systems would not be put out
by a new standard suggested by the epidemiology data. But there is an adaptation problem with the application of such lower and upper bounds. Believing that less arsenic is always better, many water system managers over the years have reduced arsenic levels in drinking water to the point where most measured arsenic levels in water systems, especially in the Eastern United States, are below 5 mg/L (US Geological Survey, 2001). To minimize cancer mortality, the Administrator must set standards that in most water systems elevate the level of arsenic.
References Chen, C.J., Chuang, Y.C., Lin, T.M., Wu, H-Y., 1985. Malignant neoplasms among residents of a Blackfoot disease-endemic area in Taiwan: High-arsenic artesian well water and cancers. Cancer Res. 45, 5895–5899. Cuzick, J., Evans, S., Gilman, M., Prince Evans, D., 1982. Medicinal arsenic and internal malignancies. Br. J. Cancer 45, 904–911. Morales, K.H., Ryan, L., Kuo, T.L., Wu, M.M., Chen, C.J., 2000. Risk of internal cancers from arsenic in drinking water. Environ. Health Perspect. 108 (7), 655–661. National Research Council (NRC), 1999. Arsenic in Drinking Water. National Academy Press, Washington, DC. National Research Council, 2001. Arsenic in Drinking Water: 2001 Update. National Academy Press, Washington, DC. US EPA, 2001. 40CFR Parts 9, 141 and 142. National primary drinking water regulations. Arsenic and clarifications to compliance and new source contaminants monitoring. Final rule. Fed. Reg. 66(14), pp. 6975–7066. US Geological Survey, 2001. http://co.water.usgs.gov/trace/pubs/ fs-063-00/fig1.gif.
Commentary
Arsenic, cancer, and thoughtless policy Gary Kayajanian* 1600 South Joyce Street, Suite 1411, Arlington, VA 22202, USA Received 13 February 2002; accepted 7 March 2002
Abstract The current drinking water contaminant standard for arsenic is 50 mg/L, as an upper bound. There is no lower bound for the standard. In an analysis of three epidemiology studies, the author demonstrates a significant cancer incidence trough for arsenic near 50 mg/L. Allowing, and even requiring, a much lower arsenic standard is not a desirable health outcome. Since most water systems currently deliver arsenic at levels below 5 mg/L, an undesirable health outcome is expected. For these systems and others not near 50 mg/L, the level of arsenic should be adjusted to bring it near 50 mg/L. r 2003 Published by Elsevier Science (USA). Keywords: Arsenic; Cancer; Anticarcinogen; J-shaped exposure–response curve
1. Introduction The finding by scientists that arsenic is a human carcinogen at prolonged high exposures is a conclusion that is of little value to regulators, because it mispredicts and misreads the carcinogenic effects of arsenic at the low levels to which man is exposed. The author has examined three epidemiology data sets to support this argument, including the very study the EPA and the NRC have relied on to defend lowering the current arsenic maximum contaminant level from 50 mg/L in drinking water (National Research Council, 1999, 2001; US EPA, 2001).
2. Methodology On a graph in which human cancer mortality rate is plotted as a function of lifetime arsenic exposure level, imagine two data points—one that represents cancer mortality at a background arsenic exposure, and a second which reports a significantly elevated cancer mortality at a high arsenic exposure level. That highdose human cancer mortality elevation is sufficient to earn the designation ‘‘carcinogen’’ for arsenic. Such a designation is applied to arsenic without regard to *Corresponding author. E-mail address: [email protected] (G. Kayajanian).
exposure level, and carries with it the assumption that if one reduces exposure to arsenic, one also reduces cancer mortality over the full exposure range from high to background to zero. Whether the pattern of cancer reduction is linear, sublinear, exponential, or some combination, as exposure to arsenic decreases, cancer mortality must also decrease. Such is the foundation of current regulatory thinking. What if there is a third data point on the graph at a low arsenic level—between background and high exposures—where cancer mortality is significantly reduced from background mortality, thereby generating an exposure–response curve with a J shape. Because of the significant low-exposure reduction in cancer mortality, arsenic should be designated an ‘‘anti-carcinogen’’, which carries with it the assumption that as one reduces arsenic exposure from low through background to zero, cancer mortality increases. Such a low-exposure data point also negates the assumption, cited above, surrounding the high-dose cancer designation of arsenic. How does one distinguish between EPA’s traditional cancer classification of arsenic where cancer mortality always decreases as arsenic exposure decreases, and the J-shaped curve I have postulated for arsenic? It is accomplished by examining the cancer mortality associated with the low-exposure region of the graph, where the two models’ predictions are opposite. First, clarification is needed. The J-shaped curve I have described is defined by three data points. My
0147-6513/03/$ - see front matter r 2003 Published by Elsevier Science (USA). doi:10.1016/S0147-6513(02)00042-8
140
G. Kayajanian / Ecotoxicology and Environmental Safety 55 (2003) 139–142
designation of these points (background, low, and high) is arbitrary and flows from my presentation of the model. If they represent the arsenic levels of an actual data set that the EPA Administrator relies on to set arsenic levels in drinking water, then she should increase the arsenic level to what corresponds to the cancer mortality trough. If the three points had different designations—say, below background, background, and high—where background corresponded to the trough, the Administrator should order no change in arsenic levels. And finally, if the three points were ‘‘further below background,’’ ‘‘below background,’’ and ‘‘high,’’ where the trough is associated with ‘‘below background,’’ she should lower the arsenic level to below background but not further. Therefore, if the J-shaped model describes the arsenic human mortality data, there is regulatory value in determining the arsenic exposure that corresponds to the cancer trough.
3. Analysis The first data set I examine is Table A10-1 of the 1999 NRC report cited above, on pp. 308 and 309. It is the Taiwan data set both EPA and the NRC relied on to draw conclusions about arsenic. That table reports the number of lung, liver, and bladder cancers in men and women in each of the 42 villages studied. Within each village these cancers are associated with a specific number of man- or woman-years of exposure. The 42 villages are rank-ordered from least to most arsenic in the drinking water, measured in units which are easily converted to micrograms per liter. Most of the villages had a single well source for water, and its arsenic level was used for the ranking. For those villages with an odd number of wells, the middle arsenic level was used to rank the village. For those villages with an even number of wells, the arithmetic mean of the middle two wells was used for ranking. For my analysis of cancer mortality in men, for arsenic exposure I grouped the villages by fives: the lowest five, the next lowest five, and so forth,y, generating nine exposure groups. For each exposure group I totaled the number of lung, liver, and bladder cancers (15 values for the first eight exposure groups) and put the sum in the numerator of a cancer measure. In the denominator I totaled the man-years associated with these cancers. For simplicity, I expressed the fraction as cancers/1000 man-years. These nine fractions are presented in Table 1. In the lowest exposure group of five villages, the number of cancers/1000 man-years is more than three times higher than in the next lowest group of five villages—a difference that is significant at Po0.001. The second lowest exposure group corresponds to the cancer mortality trough for the men.
The same process was used to analyze the cancer mortality data for the women, also presented in Table 1. In the lowest exposure group of five villages, the number of cancers/1000 woman-years is more than three times higher than in the second and third lowest exposure groups—a difference that is significant at Po0.001. The lowest exposure group included villages whose arsenic level ranged from 10 to 32 mg/L; the second group, from 42 to 60 mg/L; and the third from 65 to 110 mg/L. The EPA Administrator should establish a new arsenic standard with lower and upper bounds that correspond to the cancer mortality trough. How does this analysis differ from the Morales et al. (2000) treatment of the same data set that EPA relied on? They employed only four exposure groups, the lowest of which embraced the 13 villages with arsenic levels ranging from 0 to 100 mg/L—the five villages from my lowest exposure group, the five from my second lowest exposure group, and the next three villages. Their grouping obscured the significant mortality pattern between my lowest two exposure groups, and thereby did not contradict the traditional EPA modeling of cancer mortality data. The Utah mortality data set I employed to test my observations from the Taiwan Study was graciously provided by EPA staff, who calculated mean lifetime arsenic exposure in units convertible to micrograms per liter for each of the 4055 men and women whose deaths—some by cancer—were reported. I employed four exposure groups to measure changes in cancer mortality incidence: 0 to o25; 25 to o75; 75 to o150; and 150–175 mg/L. I employed two cancer mortality measures: the six cancer classifications which were elevated in the Taiwan data—lung, liver, bladder, kidney, colon, and melanoma—per hundred deaths (Chen et al., 1985); and total cancers per hundred deaths (Table 2). For the men, either cancer measure is higher in the lowest exposure group than in the next lowest group, but not significantly. For the women, the six-cancer measure is more than fourfold higher in the lowest exposure group than in the next lowest, which is significant (Po0.001); the total cancer measure is more than threefold higher in the lowest exposure group than in the next lowest, which is also significant (Po0.000001). For the population as a single unit, i.e., men and women combined, the six-cancer measure is 90% greater in the lowest exposure group than in the next lowest (Po0.02). The total cancer measure is 65% higher in the lowest exposure grouping than in the next lowest (Po0.001). A third data set, from the 1982 Cuzick et al.’s article in the British Journal of Cancer, is structurally different than the Taiwan and Utah data sets. The pooled population of men and women were intentionally dosed with arsenic for medicinal purposes and standardized
G. Kayajanian / Ecotoxicology and Environmental Safety 55 (2003) 139–142
141
Table 1 Taiwan’s internal cancer (lung, liver, and bladder) mortality data Village group 1
Exposure range (mg/L)
Int. cancer deaths per 1000 man years
10–32
P value and direction between groups
1.65
Int. Cancer deaths per 1000 woman years 1.62
o0.001, down 2
42–60
0.53
3
65–110
0.76
4
110–256
1.13
5
259–398
1.29
6
406–520
2.18
7
520–599
1.95
8
650–698
2.43
9
717–934
1.48
P value and direction between groups o0.001, down
0.51 o0.20, up
o0.93, up 0.52
o0.12, up
o0.05, up 0.98
o0.63, up
o0.40, down 0.75
o0.03, up
o0.11, up 1.25
o0.56, down
o0.47, up 1.49
o0.22, up
o0.17, up 1.99
o0.04, down
o0.10, down 1.29
Note. From National Research Council (1999).
Table 2 Utah cancer mortality as a function of lifetime arsenic exposure: limited cancer grouping (lung, liver, bladder, kidney, colon, and melanoma) and total cancer in men and women Exposure range (mg/L)
Size of group
Men 0 to o25
932
Number of six cancer grouping
Cancers per 100 people
25
2.682
P Value, direction between groups
Number of total cancers
Cancers per 100 people
75
8.047
o0.39, down
P value, direction between groups
o0.58, down
25 to o75
554
11
1.986
40
7.220
75 to o150
273
5
1.832
31
11.355
150–175
334
15
4.491
40
11.976
Women 0 to o25
838
22
2.625
77
9.189
13
2.784
23 57
9.504 13.735
152
8.588
53
5.191
54
10.485
97
12.951
o0.08, up o0.07, up
o0.01, down
25 to o75
467
3
0.642
75 to o150 150–175
242 415
5 10
2.066 2.410
Men+women 0 to o25
1770
47
2.655
25 to o75
1021
14
1.371
75 to o150
515
10
1.942
150–175
745
25
3.338
o0.000001, down
o0.10, up
o0.01, up
o0.02, down
o0.001, down
o0.43, up
o0.001, up
o0.13, up
cancer mortality was presented as a function of two variables: increasing total dose and time in years since the first dose (Table 3, which borrows heavily from Cuzick’s Table 3.). In this study, I view the outside reference as the lowest exposure group, and the lowest
o0.21, up
dosed group as the next lowest exposure group. In all the time intervals (0–5, 6–10, 11–20, and beyond 20 years), the lowest dosed group (p500 mg) had fewer cancers than expected from the outside reference. Over all time intervals 10 cancers were observed in the lowest
G. Kayajanian / Ecotoxicology and Environmental Safety 55 (2003) 139–142
142
Table 3 Observed (O) and expected (E) cancers by dose and time from first known treatment
Time (years) o5 5–9 10–19 X20 All years
Dose:o500 mg
500–999 mg
O
E
O
0 3 4 3 10
2.99 3.37 7.14 4.84 18.34
2 3 4 0 9
1000–1999 mg
X2000 mg
All levels
E
O
E
O
E
O
E
1.45 1.25 2.21 1.87 6.78
0 1 4 2 7
1.05 1.04 1.75 0.74 4.58
0 4 0 4 8
0.95 1.01 1.86 2.33 6.15
2 11 12 9 34
6.45 6.67 12.90 9.78 35.85
Note. From Cuzick et al. (1982).
dosed group, and 18.34 cancers were expected from the outside reference (Po0.06). At the higher dosings, 14.41 cancers were expected; 24 were observed. The most common dosing regimen in the Cuzick study was 250 mg/month, and the mean exposure time was about 9 months. Clearly, as a short-term exposure data set, Cuzick study is not equatable to Taiwan and Utah, and not helpful in establishing any exposure placement of a lifetime cancer mortality trough. Still, it establishes a J shape for the cancer mortality curve. The Cuzick data may be helpful in suggesting the effect of arsenic on cancer mortality. In the 5 years following initial arsenic medication, 6.45 cancer deaths were expected; in the second 5 years, 6.67—a total of 13.12 cancer deaths. And over those 10 years, 13 deaths were recorded: but only 2 occurred in the first 5 and 11 occurred in the second 5 years (Po0.02)—a timing which suggests that any cancers ‘‘promoted’’ in the second 5 years are entirely offset by those prevented in the first 5 years.
4. Discussion In the past a drinking water contaminant level has been set as an upper bound only. The preceding analysis of arsenic epidemiology data concludes that for this chemical both a lower and an upper bound limit are desirable, and these bounds span the current upper limit of 50 mg/L. If current arsenic contaminant levels were just below the current 50 mg/L, water systems would not be put out
by a new standard suggested by the epidemiology data. But there is an adaptation problem with the application of such lower and upper bounds. Believing that less arsenic is always better, many water system managers over the years have reduced arsenic levels in drinking water to the point where most measured arsenic levels in water systems, especially in the Eastern United States, are below 5 mg/L (US Geological Survey, 2001). To minimize cancer mortality, the Administrator must set standards that in most water systems elevate the level of arsenic.
References Chen, C.J., Chuang, Y.C., Lin, T.M., Wu, H-Y., 1985. Malignant neoplasms among residents of a Blackfoot disease-endemic area in Taiwan: High-arsenic artesian well water and cancers. Cancer Res. 45, 5895–5899. Cuzick, J., Evans, S., Gilman, M., Prince Evans, D., 1982. Medicinal arsenic and internal malignancies. Br. J. Cancer 45, 904–911. Morales, K.H., Ryan, L., Kuo, T.L., Wu, M.M., Chen, C.J., 2000. Risk of internal cancers from arsenic in drinking water. Environ. Health Perspect. 108 (7), 655–661. National Research Council (NRC), 1999. Arsenic in Drinking Water. National Academy Press, Washington, DC. National Research Council, 2001. Arsenic in Drinking Water: 2001 Update. National Academy Press, Washington, DC. US EPA, 2001. 40CFR Parts 9, 141 and 142. National primary drinking water regulations. Arsenic and clarifications to compliance and new source contaminants monitoring. Final rule. Fed. Reg. 66(14), pp. 6975–7066. US Geological Survey, 2001. http://co.water.usgs.gov/trace/pubs/ fs-063-00/fig1.gif.