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Nuevas evidencias sobre los
efectos crónicos de la
exposición a arsénico en agua
potable en Chile.
Catterina Ferreccio Readi
Departamento de Salud Pública
www.saludpublicauc.cl
Pontificia Universidad Católica de Chile
Santiago 2013
Regiones del Norte de Chile
Lugar más
seco del
mundo
Pocas fuentes
de agua
Todos toman
agua de la misma
fuente
Hay registros históricos de
los niveles de As en todas las
fuentes de agua
+
Arsénico en agua potable 1950-04 (µg/L)
Años Antof. Tocopilla Calama
1930-57 90 250 150
1958-70 860 250 150
1971-77 110 636 287
1978-79 110 110 110
1980-87 70 110 110
1988-94 40 40 40
1995-03 40 40 40
2004-05 10 10 10
Prom ajustado de As ( g/L) agua Reg II, 50-94
Short term effects: Neonatal mortality rates for
Antofagasta and Valparaiso, 1950 to 1996.
Chronic Arsenic Exposure and Risk of Infant Mortality in Two Areas of Chile.
Environmental Health Perspectives 2000. 108 (1) 7
Late fetal mortality rates for Antofagasta and
Valparaiso, 1950 to 1996. Environmental Health Perspectives
0.5
1
1.5
2
1950 1960 1970 1980 1990 2000
Year
RateRatios
Male Female
Acute Myocardial Infarction Mortality Region II of
Chile from 1950 to 2000
High As Exposure
Period
Yuan Y. et al. Am J Epidemiol. 2007.
Exposición
niñez
Expuesto sólo
como adultos
Mortalidad (SMRs) EPOC, edad 30-49 años,
expuestos in-utero o expuestos en la niñez
Smith AH, Marshall G, Yuan Y, Ferreccio C, Liaw J, von Ehrenstein OS, Steinmaus1, Bates MN, and Selvin
S. Environ Health Perspect 114:1293-96, 2006.
Evidence From Chile That Arsenic in
Drinking Water May Increase Mortality From
Pulmonary Tuberculosis
American Journal of Epidemiology
Mortality in young adults following in utero and
early childhood exposure to arsenic in drinking
water
RIESGO DE CANCER PULMONAR INTERACCION
ARSENICO/TABACO. Casos y Controles. 1994-1996
Smoking
category
Arsenic
(µg/L)a
Bladder cancer Lung cancer
OR OR
Never-smoker <11 1.00 1.00
11-91 2.66 0.68
92-335 7.01 0.93
>335 8.86 2.04
Heavier
smoker
<11 4.12 3.75
11-91 4.72 4.39
92-335 7.08 12.4
>335 23.21 16.26
OR for Bladder and Lung Cancer and Arsenic in Water,
by Smoking Status, Northern Chile, 2007-2010
Cancer OR; only cases histologically confirmed, non-
proxy, sex. Upper/lower quart avge lifetime As concentr
prior to 1971
OR adjusted for age, sex, smoking, mining work, race, body-mass index, and
SES. bladder ca OR in females of 23.6 (4.14-135.3) is truncated.
Lung Ca OR in Men by As an other
exposures, 2007-2010 (Epidem 2013)
Other
agent:
Exposed Unexposed Exposed
Synergy index
Arsenic:a Low exposure High exposure High exposure
OR (95% CI) OR (95% CI) OR (95% CI) S (95% CI)
Any
carcinogen
1.8 (0.6- 5.4) 5.2 (1.8-15.3) 12.1 (3.8-38.4) 2.2 (0.9-5.5)
Asbestos 1.6 (0.1-17.8) 6.0 (2.8-12.3) 16.2 (2.8-95.1) 2.7 (0.5-14.4)
Silica 1.8 (0.6- 5.6) 6.2 (2.6-14.8) 13.0 (3.9-42.8) 2.0 (0.8-5.2)
Wood dust 2.5 (0.8- 7.7) 7.6 (3.2-17.9) 26.5 (6.0-116.8) 3.1 (1.1-9.3)
Welding
fumes
1.0 (0.3- 3.2) 5.6 (2.4-12.8) 11.9 (3.7-38.1) 2.4 (0.8-7.1)
Coke oven 0.9 (0.2- 3.6) 6.0 (2.7-13.0) 6.5 (2.2-19.2) 1.1 (0.4-3.1)
Soot 1.7 (0.4- 6.5) 6.3 (2.9-13.5) 16.1 (2.2-117.0) 2.5 (0.6-11.3)
Fiberglass 1.4 (0.2- 7.4) 6.1 (2.9-12.8) 14.4 (2.6-80.6) 2.5 (0.6-10.9)
Kidney Cancer OR by As Intake and Histologic
Subtype, Chile, 2007-10
Type of cancer Renal pelvis & ureter Renal cell
Exposure
As
intake
Contr Case OR 95% CI
No.
Cases
OR 95% CI
Lifetime
average
(µg/day)
<48 219 1 1.00 26 1.00
48-167 211 3 4.68 0.3, 67.3 32 1.29 0.7. 2.3
>167 210 14 19.3 2.4, 154.4 23 1.01 0.5, 1.9
p-trend=0.0006 p-trend=0.98
Cum. expos
(mg)
Before
1971
<0.7 218 1 1.00 27 1.00
0.7-6.1 213 3 4.83 0.4, 60.6 28 1.27 0.7, 2.3
>6.1 205 14 19.0 2.4-152.7 24 1.24 0.7, 2.3
p-trend=0.0003 p-trend=0.5
Early-life As and lung function residuals (observed
minus predicted) and %of age-, sex-, and height-
predicted values (mean ± SD)
Peak arsenic before age 10
<50 μg/l
(n = 45)
50–250 μg/l
(n = 20)
>800 μg/l
(n = 32)
Percent predicted
FEV1
98.2 ± 14.6 91.2 ± 11.0 88.1 ± 18.3
Percent predicted
FVC
103.6 ± 16.7 98.2 ± 10.0 94.7 ± 15.3
FEV1 residual
(ml)
−63 ± 443 −270 ± 314 −375 ± 611
FVC residual (ml) 103 ± 584 −54 ± 380 −226 ± 614
Temas de investigación en desarrollo
• Duración del riesgo luego de detenida la
exposición
• Riesgo de otros cánceres como mama y
próstata
• Identificar bio-marcadores de riesgo para
detección precoz
Protección a la población expuesta
Prevención primaria:
1. As: mantener en el agua <10 ug/L
(Norma Regional menor?)
2. Reducir exposición al tabaco
3. Promover: frutas-verduras, actividad
física.
Prevención Secundaria
1. Alertar al cuerpo médico
2. Tamizaje?
References
• Ferreccio C, C. Arsenic, tobacco smoke, and occupation: associations of multiple agents with
lung and bladder cancer. Epidemiology. 2013 Nov;24(6):898-905.
• Ferreccio C, Case-control study of arsenic in drinking water and kidney cancer in uniquely
exposed northern chile. Am J Epidemiol. 2013 Sep 1;178(5):813-8.
• Steinmaus CM, Drinking water arsenic in northern chile: high cancer risks 40 years after exposure
cessation. Cancer Epidemiol Biomarkers Prev. 2013 Apr;22(4):623-30. d
• Smith AH,. Mortality in young adults following in utero and childhood exposure to arsenic in
drinking water. Environ Health Perspect. 2012 Nov;120(11):1527-31.
• Smith AH, Evidence from Chile that arsenic in drinking water may increase mortality from
pulmonary tuberculosis. Am J Epidemiol. 2011 Feb 15;173(4):414-20.
• Dauphiné DC Lung function in adults following in utero and childhood exposure to arsenic in
drinking water: preliminary findings. Int Arch Occup Environ Health. 2011 Aug;84(6):591-600.
• Yuan Y, Marshall G, Ferreccio C, Steinmaus C, Liaw J, Bates M, Smith AH. Kidney cancer
mortality: fifty-year latency patterns related to arsenic exposure. Epidemiology. 2010
Jan;21(1):103-8.
• Liaw J, Increased childhood liver cancer mortality and arsenic in drinking water in northern Chile.
Cancer Epidemiol Biomarkers Prev. 2008 Aug;17(8):1982-7.
• Yuan Y, Acute myocardial infarction mortality in comparison with lung and bladder cancer
mortality in arsenic-exposed region II of Chile from 1950 to 2000. Am J Epidemiol. 2007 Dec
15;166(12):1381-91.
• Marshall G, Fifty-year study of lung and bladder cancer mortality in Chile related to arsenic in
drinking water. J Natl Cancer Inst. 2007 Jun 20;99(12):920-8.
• Smith AH, Increased mortality from lung cancer and bronchiectasis in young
adults after exposure to arsenic in utero and in early childhood. Environ
Health Perspect. 2006 Aug;114(8):1293-6.
• Ferreccio C. [Bronchopulmonary cancer in workers exposed to arsenic: a
case control study]. Rev Med Chil. 1996 Jan;124(1):119-23.
• Ferreccio C, Arsenic exposure and its impact on health in Chile. J Health
Popul Nutr. 2006 Jun;24(2):164-75. Review.
• Hopenhayn C, Profile of urinary arsenic metabolites during pregnancy.
Environ Health Perspect. 2003 Dec;111(16):1888-91.
• Moore LE,. P53 alterations in bladder tumors from arsenic and tobacco
exposed patients. Carcinogenesis. 2003 Nov;24(11):1785-91.
• Moore LE,. Arsenic-related chromosomal alterations in bladder cancer. J
Natl Cancer Inst. 2002 Nov 20;94(22):
• Ferreccio C, Lung cancer and arsenic concentrations in drinking water in
Chile. Epidemiology. 2000 Nov;11(6):673-9.
• Hopenhayn-Rich C,. Chronic arsenic exposure and risk of infant mortality in
two areas of Chile. Environ Health Perspect. 2000 Jul;108(7):667-73.
• Biggs ML, Arsenic-laced water in Chile. Science. 1998 Aug
7;281(5378):785. PubMed PMID: 9714681.

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Catterina ferreccio nuevas evidencias sobre los efectos crónicos de la exposición a arsénico en agua potable en chile

  • 1. Nuevas evidencias sobre los efectos crónicos de la exposición a arsénico en agua potable en Chile. Catterina Ferreccio Readi Departamento de Salud Pública www.saludpublicauc.cl Pontificia Universidad Católica de Chile Santiago 2013
  • 2. Regiones del Norte de Chile Lugar más seco del mundo Pocas fuentes de agua Todos toman agua de la misma fuente Hay registros históricos de los niveles de As en todas las fuentes de agua +
  • 3. Arsénico en agua potable 1950-04 (µg/L) Años Antof. Tocopilla Calama 1930-57 90 250 150 1958-70 860 250 150 1971-77 110 636 287 1978-79 110 110 110 1980-87 70 110 110 1988-94 40 40 40 1995-03 40 40 40 2004-05 10 10 10
  • 4. Prom ajustado de As ( g/L) agua Reg II, 50-94
  • 5. Short term effects: Neonatal mortality rates for Antofagasta and Valparaiso, 1950 to 1996. Chronic Arsenic Exposure and Risk of Infant Mortality in Two Areas of Chile. Environmental Health Perspectives 2000. 108 (1) 7
  • 6. Late fetal mortality rates for Antofagasta and Valparaiso, 1950 to 1996. Environmental Health Perspectives
  • 7. 0.5 1 1.5 2 1950 1960 1970 1980 1990 2000 Year RateRatios Male Female Acute Myocardial Infarction Mortality Region II of Chile from 1950 to 2000 High As Exposure Period Yuan Y. et al. Am J Epidemiol. 2007.
  • 8.
  • 9.
  • 11. Mortalidad (SMRs) EPOC, edad 30-49 años, expuestos in-utero o expuestos en la niñez Smith AH, Marshall G, Yuan Y, Ferreccio C, Liaw J, von Ehrenstein OS, Steinmaus1, Bates MN, and Selvin S. Environ Health Perspect 114:1293-96, 2006.
  • 12.
  • 13. Evidence From Chile That Arsenic in Drinking Water May Increase Mortality From Pulmonary Tuberculosis American Journal of Epidemiology
  • 14. Mortality in young adults following in utero and early childhood exposure to arsenic in drinking water
  • 15. RIESGO DE CANCER PULMONAR INTERACCION ARSENICO/TABACO. Casos y Controles. 1994-1996
  • 16. Smoking category Arsenic (µg/L)a Bladder cancer Lung cancer OR OR Never-smoker <11 1.00 1.00 11-91 2.66 0.68 92-335 7.01 0.93 >335 8.86 2.04 Heavier smoker <11 4.12 3.75 11-91 4.72 4.39 92-335 7.08 12.4 >335 23.21 16.26 OR for Bladder and Lung Cancer and Arsenic in Water, by Smoking Status, Northern Chile, 2007-2010
  • 17. Cancer OR; only cases histologically confirmed, non- proxy, sex. Upper/lower quart avge lifetime As concentr prior to 1971 OR adjusted for age, sex, smoking, mining work, race, body-mass index, and SES. bladder ca OR in females of 23.6 (4.14-135.3) is truncated.
  • 18. Lung Ca OR in Men by As an other exposures, 2007-2010 (Epidem 2013) Other agent: Exposed Unexposed Exposed Synergy index Arsenic:a Low exposure High exposure High exposure OR (95% CI) OR (95% CI) OR (95% CI) S (95% CI) Any carcinogen 1.8 (0.6- 5.4) 5.2 (1.8-15.3) 12.1 (3.8-38.4) 2.2 (0.9-5.5) Asbestos 1.6 (0.1-17.8) 6.0 (2.8-12.3) 16.2 (2.8-95.1) 2.7 (0.5-14.4) Silica 1.8 (0.6- 5.6) 6.2 (2.6-14.8) 13.0 (3.9-42.8) 2.0 (0.8-5.2) Wood dust 2.5 (0.8- 7.7) 7.6 (3.2-17.9) 26.5 (6.0-116.8) 3.1 (1.1-9.3) Welding fumes 1.0 (0.3- 3.2) 5.6 (2.4-12.8) 11.9 (3.7-38.1) 2.4 (0.8-7.1) Coke oven 0.9 (0.2- 3.6) 6.0 (2.7-13.0) 6.5 (2.2-19.2) 1.1 (0.4-3.1) Soot 1.7 (0.4- 6.5) 6.3 (2.9-13.5) 16.1 (2.2-117.0) 2.5 (0.6-11.3) Fiberglass 1.4 (0.2- 7.4) 6.1 (2.9-12.8) 14.4 (2.6-80.6) 2.5 (0.6-10.9)
  • 19. Kidney Cancer OR by As Intake and Histologic Subtype, Chile, 2007-10 Type of cancer Renal pelvis & ureter Renal cell Exposure As intake Contr Case OR 95% CI No. Cases OR 95% CI Lifetime average (µg/day) <48 219 1 1.00 26 1.00 48-167 211 3 4.68 0.3, 67.3 32 1.29 0.7. 2.3 >167 210 14 19.3 2.4, 154.4 23 1.01 0.5, 1.9 p-trend=0.0006 p-trend=0.98 Cum. expos (mg) Before 1971 <0.7 218 1 1.00 27 1.00 0.7-6.1 213 3 4.83 0.4, 60.6 28 1.27 0.7, 2.3 >6.1 205 14 19.0 2.4-152.7 24 1.24 0.7, 2.3 p-trend=0.0003 p-trend=0.5
  • 20. Early-life As and lung function residuals (observed minus predicted) and %of age-, sex-, and height- predicted values (mean ± SD) Peak arsenic before age 10 <50 μg/l (n = 45) 50–250 μg/l (n = 20) >800 μg/l (n = 32) Percent predicted FEV1 98.2 ± 14.6 91.2 ± 11.0 88.1 ± 18.3 Percent predicted FVC 103.6 ± 16.7 98.2 ± 10.0 94.7 ± 15.3 FEV1 residual (ml) −63 ± 443 −270 ± 314 −375 ± 611 FVC residual (ml) 103 ± 584 −54 ± 380 −226 ± 614
  • 21. Temas de investigación en desarrollo • Duración del riesgo luego de detenida la exposición • Riesgo de otros cánceres como mama y próstata • Identificar bio-marcadores de riesgo para detección precoz
  • 22. Protección a la población expuesta Prevención primaria: 1. As: mantener en el agua <10 ug/L (Norma Regional menor?) 2. Reducir exposición al tabaco 3. Promover: frutas-verduras, actividad física. Prevención Secundaria 1. Alertar al cuerpo médico 2. Tamizaje?
  • 23. References • Ferreccio C, C. Arsenic, tobacco smoke, and occupation: associations of multiple agents with lung and bladder cancer. Epidemiology. 2013 Nov;24(6):898-905. • Ferreccio C, Case-control study of arsenic in drinking water and kidney cancer in uniquely exposed northern chile. Am J Epidemiol. 2013 Sep 1;178(5):813-8. • Steinmaus CM, Drinking water arsenic in northern chile: high cancer risks 40 years after exposure cessation. Cancer Epidemiol Biomarkers Prev. 2013 Apr;22(4):623-30. d • Smith AH,. Mortality in young adults following in utero and childhood exposure to arsenic in drinking water. Environ Health Perspect. 2012 Nov;120(11):1527-31. • Smith AH, Evidence from Chile that arsenic in drinking water may increase mortality from pulmonary tuberculosis. Am J Epidemiol. 2011 Feb 15;173(4):414-20. • Dauphiné DC Lung function in adults following in utero and childhood exposure to arsenic in drinking water: preliminary findings. Int Arch Occup Environ Health. 2011 Aug;84(6):591-600. • Yuan Y, Marshall G, Ferreccio C, Steinmaus C, Liaw J, Bates M, Smith AH. Kidney cancer mortality: fifty-year latency patterns related to arsenic exposure. Epidemiology. 2010 Jan;21(1):103-8. • Liaw J, Increased childhood liver cancer mortality and arsenic in drinking water in northern Chile. Cancer Epidemiol Biomarkers Prev. 2008 Aug;17(8):1982-7. • Yuan Y, Acute myocardial infarction mortality in comparison with lung and bladder cancer mortality in arsenic-exposed region II of Chile from 1950 to 2000. Am J Epidemiol. 2007 Dec 15;166(12):1381-91. • Marshall G, Fifty-year study of lung and bladder cancer mortality in Chile related to arsenic in drinking water. J Natl Cancer Inst. 2007 Jun 20;99(12):920-8.
  • 24. • Smith AH, Increased mortality from lung cancer and bronchiectasis in young adults after exposure to arsenic in utero and in early childhood. Environ Health Perspect. 2006 Aug;114(8):1293-6. • Ferreccio C. [Bronchopulmonary cancer in workers exposed to arsenic: a case control study]. Rev Med Chil. 1996 Jan;124(1):119-23. • Ferreccio C, Arsenic exposure and its impact on health in Chile. J Health Popul Nutr. 2006 Jun;24(2):164-75. Review. • Hopenhayn C, Profile of urinary arsenic metabolites during pregnancy. Environ Health Perspect. 2003 Dec;111(16):1888-91. • Moore LE,. P53 alterations in bladder tumors from arsenic and tobacco exposed patients. Carcinogenesis. 2003 Nov;24(11):1785-91. • Moore LE,. Arsenic-related chromosomal alterations in bladder cancer. J Natl Cancer Inst. 2002 Nov 20;94(22): • Ferreccio C, Lung cancer and arsenic concentrations in drinking water in Chile. Epidemiology. 2000 Nov;11(6):673-9. • Hopenhayn-Rich C,. Chronic arsenic exposure and risk of infant mortality in two areas of Chile. Environ Health Perspect. 2000 Jul;108(7):667-73. • Biggs ML, Arsenic-laced water in Chile. Science. 1998 Aug 7;281(5378):785. PubMed PMID: 9714681.