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ISEE/ISEA Conference, Athens, Greece, September 1999 ARSENIC-CONTAMINATED WELL WATER AND SKIN DISORDERS IN HUHHOT, INNER MONGOLIA (IMCAP) Presented By:

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1 ISEE/ISEA Conference, Athens, Greece, September 1999 ARSENIC-CONTAMINATED WELL WATER AND SKIN DISORDERS IN HUHHOT, INNER MONGOLIA (IMCAP) Presented By: Richard Wilson Harvard University

2 ISEE/ISEA Conference, Athens, Greece, September 1999 The Inner Mongolia Collaborative Project is to help the Chinese analyze, and extend their data and bring them to public attention. Hohhot Sanitation and Anti-Epidemic Station Dr. Luo Zhengdong, Dr Zhang Yu-Min and other collaborators. Institute of Environmental Health and Engineering, Chinese Academy of Preventive Medicine in Beijing Dr. He Xingzhou Consultants in Epidemiology and Occupational Health (CEOH) in Washington, D.C., Dr. Steven Lamm, Dr Li Feng Xiao University of Texas, Austin, Dr Steven Tucker Medical School, University of Miami, Dr. Lai Shenghan Consultant, Dr Dan Byrd Harvard University, Dr. Richard Wilson

3 ISEE/ISEA Conference, Athens, Greece, September 1999 Distribution of individuals with Different Exposure/Outcome Status E/O# of SubjAge  SDGender _______Race____________________ Status(N)(years)M (%)F (%)H (%)M (%) _____________________________________________________________________ Known317933  201628 (51)1551(49)3172 (99.8)7 (0.2) Unknown 497  10 22 (45)27 (55)49 (100.0)0 (0.0) Total322832  201650 (51)1578 (49)3221 (99.8)7 (0.2) _____________________________________________________________________

4 ISEE/ISEA Conference, Athens, Greece, September 1999 Demographic distribution in three selected villages # of Subj.Age  SD Gender___ Race____________ Village(N)(years)M (%)F (%)H (%)M (%) ____________________________________________________________________ Hei He175536  19901 (51)854 (49)1748 (99.6)7 (0.4) Tie MG25727  19128 (50)129 (50)257 (100)0 (0.0) Zhi JL1167 30  19599 (51)568 (49)1167 (100)0 (0.0) ____________________________________________________________________

5 ISEE/ISEA Conference, Athens, Greece, September 1999 Distribution of the study population by age groups and by villages Age (yrs)Hei He____Tie Men GengZhi Ji LiangTotal______ n%n%n%n __________________________________________________________________________________________________ <101176.76425.021518.439612.5 10-1932618.63814.819116.455517.5 20-2934619.84919.126222.565720.7 30-3930817.65320.719416.655517.5 40-4925914.8124.7927.936311.4 50-591649.4218.21008.62859.0 60-691307.4114.3786.72196.9 70+1025.883.1353.01454.6 __________________________________________________________________________________________________ Total1752100.0256100.01167100.03175 100.0

6 ISEE/ISEA Conference, Athens, Greece, September 1999 Frequency distribution of wells and statistics of As concentration Frq. by sample #___ Frq. by As concentration grps As concentration statistics (ppb) Village One Two Three<10 10- 50- 150- 500+Mn Std. Min P25 Med P75 Max ______________________________________________________________________________________________________________ Hei He 76 2 1 1 29 46 3 0 65 35 537 57 81 176 Tie MG34 11 08 16 16 4 1 75 106 520 48 80 615 Zhi JL55 5 0 35 13 1 4 7 156 386 5 5 5 27 2000 ______________________________________________________________________________________________________________ Total165 18 144 58 63 11 897 230 514 43 80 2000

7 ISEE/ISEA Conference, Athens, Greece, September 1999 Descriptive statistics of As concentration & cumulative As dosage Exposure N A-Mean A-Std. G-Mean G-Std Min P25 Med P75 Max__ MaxCon 317985.2133.5 50.0 3.0 5.0 30.0 58.0 110.0 2000.0 CumDose 3179 1571.0 1982.1 740.0 4.2 5.0 300.0 948.0 2184.0 20372.0 _____________________________________________________________________________________________________________

8 ISEE/ISEA Conference, Athens, Greece, September 1999 Descriptive statistics for the eight Maximum Arsenic Concentration (MAC) groups (ppb) MAC (ppb)NA-meanA-SDG-MNG-SDMinP25MedP75Max _______________________________________________________________________________________________________________________________________ <102875.00.05.01.055555 10-40514.74.714.11.31013131728 30-41232.83.332.61.13030343449 50-51654.93.154.81.15052565859 60-56570.39.469.71.16062628192 100-536121.718.6120.31.2100105115147147 150-416174.632.8172.51.2156158158182345 500+ 421048.3423.2974.91.558061596111742000 _______________________________________________________________________________________________________________________________________

9 ISEE/ISEA Conference, Athens, Greece, September 1999 Descriptive statistics for the eight Cumulative Arsenic Dose (CAD) groups (ppb-year) CAD NA-meanA-SDG-MNG-SDMinP25MedP75Max __________________________________________________________________________________________________________________________________________ <10 750.05.01.055555 10- 9720.17.218.71.51015202631 32- 18061.820.058.51.43445608098 100- 554202.564.6191.91.4100150196260315 316- 800617.1198.2584.91.4318442590780999 1000- 11231893.0602.81796.61.410001352185623573154 3162- 3804656.51507.54461.91.331633590413052549761 10000+ 3712971.22425.012772.81.21005910955127401491220372 ___________________________________________________________________________________________________________________________________________

10 ISEE/ISEA Conference, Athens, Greece, September 1999 Cumulative % by Max. As Conc. Cumulative Percentage Maximum As Concentration [ppb] <1010-30-50-60-100-150-500+ 0.2.4 6 8 1

11 ISEE/ISEA Conference, Athens, Greece, September 1999 Cumulative % by Cum. As Dosage

12 ISEE/ISEA Conference, Athens, Greece, September 1999 Duration and density of exposure by Maximum As Concentration MAC NExp. Duration (yrs) Exp. Density Cum. Percentage Groups(Mean  Std.)(person-yrs) of Exp Den(%) _____________________________________________________________________________ <1028721  195,8857.4 10-40523  189,23919.0 30-41222  198,96830.3 50-51625  1812,69646.3 60-56528  1915,83666.3 100-53625  1713,64583.4 150-41629  1811,97598.5 500+4228  151,180100.0 ____________________________________________________________________________ Total3,17925  1879,424

13 ISEE/ISEA Conference, Athens, Greece, September 1999 Duration and density of exposure by cumulative As dosage CAD groups NExp. Duration (yrs) Exp. Density Cum. Percentage (Mean  Std.) (person-yrs) of Exp Den (%) ____________________________________________________________________________ <1071  070.0 10-973  23300.4 32-1807  511971.9 100-55415  13830612.4 316-80020  151580632.3 1000-112331  143452375.8 3162-38046  171749697.8 10000+3748  191759100.0 Total317825  1879424

14 ISEE/ISEA Conference, Athens, Greece, September 1999 Relationship between max. As concentration (ppb) and hyperkeratosis HyperkeratosisCases SubjectsPrev. (%)ExpectedObs/Exp <1012870.3515.50.06 10-14050.2521.90.05 30-44120.9722.30.18 50-85161.5527.90.29 60-235654.0730.60.75 100-6153611.3829.02.10 150-4541610.8222.52.00 500+294269.052.312.76 Total17231795.41172.01.00 Linear trend in proportion:  2 =191, p<0.001

15 ISEE/ISEA Conference, Athens, Greece, September 1999 Relationship between max. As concentration (ppb) and dyspigmentation Dyspigmentation CasesSubjectsPrev. (%)ExpectedObs/Exp <1032871.0510.90.27 10-04050.0015.40.00 30-44120.9715.70.26 50-75161.3619.60.36 60-115651.9521.50.51 100-425367.8420.42.06 150-344168.1715.82.15 500+204247.621.612.51 Total12131793.81121.01.00 Linear trend in proportion:  2 =123, p<0.001

16 ISEE/ISEA Conference, Athens, Greece, September 1999 Relationship between max. As concentration (ppb) and Kerato-Dyspigm Kerato+DyspigmCasesSubjectsPrev. (%)ExpectedObs/Exp <1012870.35.490.12 10-04050.0011.980.00 30-34120.7312.180.25 50-65161.1615.260.39 60-115651.9516.710.66 100-315365.7815.851.96 150-244165.7712.301.95 500+184242.861.2414.49 Total9431792.9694.001.00 Linear trend in proportion:  2 =101, p<0.001

17 ISEE/ISEA Conference, Athens, Greece, September 1999 Relationship between max. As concentration (ppb) and Skin Cancer Skin CancerCasesSubjects Prev. (%)ExpectedObs/Exp <1002870.000.720.00 10-04050.001.020.00 30-04120.001.040.00 50-05160.001.300.00 60-05650.001.420.00 100-05360.001.350.00 150-54161.201.054.78 500+3427.140.1128.38 Total831790.258.001.00 Linear trend in proportion:  2 =21, p<0.001

18 ISEE/ISEA Conference, Athens, Greece, September 1999 Prevalence of Four Outcomes by Max. As Concentration

19 ISEE/ISEA Conference, Athens, Greece, September 1999 Obs/Exp Ratio by Max. As Concentration Observed/Expected Ratio Maximum As Concentration [ppb] 0 10 20 30 Skin Cancer Keratosis+Dyspigmentation Dyspigmentation Keratosis <10 10- 30- 50- 60- 100- 150- 500+

20 ISEE/ISEA Conference, Athens, Greece, September 1999 Relationship between cum. As dosage (ppb-years) and hyperkeratosis HyperkerotosisCases SubjectsPrev. (%)ExpectedObs/Exp <10070.000.40.00 10-0970.005.20.00 32-01800.009.70.00 100-25540.3630.00.07 316-128001.5043.30.28 1000-7711236.8660.81.27 3162-6438016.8420.63.11 10000+173745.952.08.49 Total17231785.41172.01.00 Linear trend in proportion:  2 =175, p<0.001

21 ISEE/ISEA Conference, Athens, Greece, September 1999 Relationship between cum. As dosage (ppb-years) and Dyspigmentation DyspigmentationCases SubjectsPrev. (%)ExpectedObs/Exp <10070.000.30.00 10-0970.003.70.00 32-11800.566.90.15 100-25540.3621.10.09 316-78000.8830.50.23 1000-5611234.9942.81.31 3162-4338011.3214.52.97 10000+123732.431.48.52 Total12131783.81121.01.00 Linear trend in proportion:  2 =114, p<0.001

22 ISEE/ISEA Conference, Athens, Greece, September 1999 Relationship between cum. As dosage (ppb-years) and Kerato-Dyspigm Kerato+DyspigmCases SubjectsPrev. (%)ExpectedObs/Exp <10070.000.20.00 10-0970.002.90.00 32-01800.005.30.00 100-15540.1816.40.06 316-58000.6323.70.21 1000-4411233.9233.21.32 3162-353809.2111.23.11 10000+93724.321.18.22 Total9431782.9694.01.00 Linear trend in proportion:  2 =95, p<0.001

23 ISEE/ISEA Conference, Athens, Greece, September 1999 Relationship between cum. As dosage (ppb-years) and Skin Cancer Skin CancerCases SubjectsPrev. (%)ExpectedObs/Exp <10070.000.00.00 10-0970.000.20.00 32-01800.000.50.00 100-05540.001.40.00 316-08000.002.00.00 1000-411230.362.81.41 3162-33800.791.03.14 10000+1372.700.110.74 Total831780.258.01.00 Linear trend in proportion:  2 =10, p<0.002

24 ISEE/ISEA Conference, Athens, Greece, September 1999 Prevalence of the four skin disorders by cum. As dosage Prevalence [%] Cumulative As Dosage [ppb_years] 0 20 40 60 Skin Cancer Kerotosis+Dyspigmentation Dyspigmentation Kerotoses <10 10- 32- 100- 316- 1000- 3162- 10000+

25 ISEE/ISEA Conference, Athens, Greece, September 1999 Obs/Exp Ratio by Cum. As Dosage Observed/Expected Ratio Cumulative As Dosage [ppb_years] 0 2 4 6 8 10 Skin Cancer Kerotosis+Dyspigmentation Dyspigmentation Kerotoses <10 10- 32- 100- 316- 1000- 3162- 10000+

26 ISEE/ISEA Conference, Athens, Greece, September 1999 Prevalence (%) of skin disorders adjusted by age and sex for MAC measure Maximum As Concentration Groups (ppb) ____________________________________________________________________________ Skin Disorders <1010-30-50-60-100-150-500+ ______________________________________________________________________________________________________ Hyperkeratosis 0.40.31.01.63.511.09.471.9 Dyspigmentation 1.10.01.11.41.67.87.053.7 Kerato+Dyspig 0.40.00.81.21.65.84.848.1 Skin Cancer 0.00.00.00.00.00.01.05.9

27 ISEE/ISEA Conference, Athens, Greece, September 1999 Prevalence (%) of skin disorders adjusted by age and sex for CAD measure Cumulative As Dosage Groups (ppb-years) _____________________________________________________________________________________ Skin Disorders <1010-30-50-60-100-150-500+ _____________________________________________________________________________________ Hyperkeratosis0.00.00.00.42.05.822.554.2 Dyspigmentation0.00.00.50.41.24.316.053.3 Kerato+Dyspig0.00.00.00.21.03.014.239.1 Skin Cancer0.00.00.00.00.00.30.22.0

28 ISEE/ISEA Conference, Athens, Greece, September 1999 Age-Sex Adjusted Prevalence by Max. As Concentration Age-sex Standardized Prevalence [%] Maximum As Concentration [ppb] 0 20 40 60 80 Skin Cancer Keratosis+Dyspigmentation Dyspigmentation Keratosis <10 10- 30- 50- 60- 100- 150- 500+

29 ISEE/ISEA Conference, Athens, Greece, September 1999 Age-Sex Adjusted Prevalence by Cum. As Dosage Observed/Expected Ratio Cumulative As Dosage [ppb_years] 0 2 4 6 8 10 Skin Cancer Kerotosis+Dyspigmentation Dyspigmentation Kerotoses <10 10- 32- 100- 316- 1000- 3162- 10000+

30 ISEE/ISEA Conference, Athens, Greece, September 1999 Eight skin cancer cases and their demographic and exposure characteristics Date of Case#HholdAgeSexRaceOccupOnsetDiagWell MACDur CAD ______________________________________________________________________________________________________________________________________________ 1GLJ65MHanFarmer19801996101022061540 9624 2GLW58MHanFarmer19851998101022061537 2195 3ZHL59FHanFarmer19721992101022061552 12858 4LYZ71FHanFarmer19851994114070217651 4147 5MJX44MHanFarmer19861996114070217643 2692 6ZM62MHanFarmer19851992114070217660 6191 7MHK71MHanFarmer19871998114070515857 2827 8WER59FHanFarmer19871994114070515836 1299

31 ISEE/ISEA Conference, Athens, Greece, September 1999 Age-Sex Adjusted Prevalence by Cum. As Dosage Age-Sex Standardized Prevalence [%] Cumulative As Dosage [ppb_years] 0 20 40 60 Skin Cancer Kerotosis+Dyspigmentation Dyspigmentation Kerotosis <10 10- 32- 100- 316- 1000- 3162- 10000+

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