RESUMEN
Chronic arsenic exposure has been associated with a range of neurologic, vascular, dermatologic, and carcinogenic effects. However, limited research has been directed at the association of arsenic exposure and human reproductive health outcomes. The principal aim of this study was to investigate the trends in infant mortality between two geographic locations in Chile: Antofagasta, which has a well-documented history of arsenic exposure from naturally contaminated water, and Valparaíso, a comparable low-exposure city. The arsenic concentration in Antofagasta's public drinking water supply rose substantially in 1958 with the introduction of a new water source, and remained elevated until 1970. We used a retrospective study design to examine time and location patterns in infant mortality between 1950 and 1996, using univariate statistics, graphical techniques, and Poisson regression analysis. Results of the study document the general declines in late fetal and infant mortality over the study period in both locations. The data also indicate an elevation of the late fetal, neonatal, and postneonatal mortality rates for Antofagasta, relative to Valparaíso, for specific time periods, which generally coincide with the period of highest arsenic concentration in the drinking water of Antofagasta. Poisson regression analysis yielded an elevated and significant association between arsenic exposure and late fetal mortality [rate ratio (RR) = 1.7; 95% confidence interval (CI), 1.5-1.9], neonatal mortality (RR = 1.53; CI, 1.4-1.7), and postneonatal mortality (RR = 1.26; CI, 1.2-1.3) after adjustment for location and calendar time. The findings from this investigation may support a role for arsenic exposure in increasing the risk of late fetal and infant mortality.
Asunto(s)
Arsénico/efectos adversos , Exposición a Riesgos Ambientales , Contaminantes Ambientales/efectos adversos , Mortalidad Infantil/tendencias , Chile/epidemiología , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Estudios Retrospectivos , Medición de Riesgo , Abastecimiento de AguaRESUMEN
BACKGROUND: Studies in Taiwan have found dose-response relations between arsenic ingestion from drinking water and cancers of the skin, bladder, lung, kidney and liver. To investigate these associations in another population, we conducted a study in Córdoba, Argentina, which has a well-documented history of arsenic exposure from drinking water. METHODS: Mortality from lung, kidney, liver and skin cancers during the period 1986-1991 in Córdoba's 26 counties was investigated, expanding the authors' previous analysis of bladder cancer in the province. Counties were grouped a priori into low, medium and high arsenic exposure categories based on available data. Standardized mortality ratios (SMR) were calculated using all of Argentina as the reference population. RESULTS: We found increasing trends for kidney and lung cancer mortality with arsenic exposure, with the following SMR, for men and women respectively: kidney cancer, 0.87, 1.33, 1.57 and 1.00, 1.36, 1.81; lung cancer, 0.92, 1.54, 1.77 and 1.24, 1.34, 2.16 (in all cases, P < 0.001 in trend test), similar to the previously reported bladder cancer results (0.80, 1.28, 2.14 for men, 1.22, 1.39, 1.81 for women). There was a small positive trend for liver cancer but mortality was increased in all three exposure groups. Skin cancer mortality was elevated for women only in the high exposure group, while men showed a puzzling increase in mortality in the low exposure group. CONCLUSIONS: The results add to the evidence that arsenic ingestion increases the risk of lung and kidney cancers. In this study, the association between arsenic and mortality from liver and skin cancers was not clear.
Asunto(s)
Arsénico/efectos adversos , Neoplasias Renales/mortalidad , Neoplasias Pulmonares/mortalidad , Abastecimiento de Agua , Argentina/epidemiología , Arsénico/análisis , Exposición a Riesgos Ambientales , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Masculino , Neoplasias Cutáneas/mortalidad , Neoplasias Gástricas/mortalidad , Neoplasias de la Vejiga Urinaria/mortalidad , Abastecimiento de Agua/análisisAsunto(s)
Arsénico/efectos adversos , Arsénico/metabolismo , Neoplasias/inducido químicamente , Contaminantes Químicos del Agua/efectos adversos , Estudios de Casos y Controles , Chile/epidemiología , Humanos , Neoplasias Pulmonares/epidemiología , Metilación , Neoplasias/epidemiología , Factores de Riesgo , Neoplasias de la Vejiga Urinaria/epidemiologíaRESUMEN
The purpose of this study was to investigate methods for ascertaining arsenic exposure for use in biomarker studies. Urinary arsenic concentration is considered a good measure of recent arsenic exposure and is commonly used to monitor exposure in environmental and occupational settings. However, measurements reflect exposure only in the last few days. To cover longer time periods exposure can be estimated using arsenic intake data, calculated by combining measures of environmental arsenic and inhalation/ingestion rates. We compared these different exposure assessment approaches in a population chronically exposed to arsenic in drinking water in northern Chile. The study group consisted of 232 people, some drinking water low in arsenic (15 micrograms/l) and others drinking water with high arsenic concentrations (up to 670 micrograms/l). First morning urine samples and questionnaire data, including fluid intake information, were collected from all participants. Exfoliated bladder cells were collected from male participants for the bladder cell micronuclei assay. Eight different indices of exposure were generated, six based on urinary arsenic (microgram As/l urine; microgram As/g creatinine; microgram InAs/l urine; microgram MMA/l urine; microgram DMA/l urine; microgram As/h, excreted), and two on fluid intake data (microgram As/day, ingested; microgram As/l fluid ingested-day). The relationship between the different exposure indices was explored using correlation analysis. In men, exposure indices were also related to a biomarker of effect, bladder cell micronuclei. While creatinine-adjusted urinary arsenic concentrations had the strongest correlations with the two intake estimates (r = 0.76, r = 0.81), unadjusted urinary arsenic showed the strongest relationship with bladder cell micronuclei. These data suggest that, in the case of the bladder, unadjusted urinary arsenic concentrations better reflect the effective target organ dose compared to other exposure measures for biomarker studies.
Asunto(s)
Arsénico/orina , Pruebas de Micronúcleos/métodos , Vejiga Urinaria/patología , Contaminantes Químicos del Agua/efectos adversos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Arsénico/efectos adversos , Biomarcadores , Chile , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Vejiga Urinaria/efectos de los fármacosRESUMEN
Inorganic arsenic is an established cause of lung and skin cancer. Epidemiological evidence from Taiwan suggests that arsenic causes more fatal internal cancers, with the highest relative risks reported for bladder cancer. We conducted a cross-sectional biomarker study in a Chilean male population chronically exposed to high (70 subjects) and low (55 subjects) arsenic levels in their drinking water (average concentrations, 600 and 15 micrograms As/liter, respectively). A fluorescent version of the exfoliated bladder cell micronucleus (MN) assay was used employing fluorescence in situ hybridization with a centromeric probe to identify the presence (MN+) or absence (MN-) of whole chromosomes within micronuclei, thereby determining the mechanism of arsenic-induced genotoxicity in vivo. We divided the study population into quintiles by urinary arsenic levels and found an exposure-dependent increase in micronucleated cell prevalence in quintiles 2-4 (urinary arsenic, 54-729 micrograms/liter). The largest increase appeared when quintile 4 was compared to quintile 1 [prevalence ratio, 3.0; 95% confidence interval (CI), 1.9-4.6]. The prevalence of MN+ increased to 3.1-fold in quintile 4 (95% CI, 1.4-6.6), and the prevalence of MN-increased to 7.5-fold in quintile 3 (95% CI, 2.8-20.3), suggesting that chromosome breakage was the major cause of MN formation. Prevalences of total MN, MN+, and MN- returned to baseline levels in quintile 5 (urinary arsenic, 729-1894 micrograms/liter), perhaps due to cytostasis or cytotoxicity. These results add additional weight to the hypothesis that ingesting arsenic-contaminated water enhances bladder cancer risk and suggest that arsenic induces genetic damage to bladder cells at drinking water levels close to the current United States Maximum Contaminant Level of 50 micrograms/liter for arsenic.
Asunto(s)
Arsénico/efectos adversos , Biomarcadores de Tumor , Exposición a Riesgos Ambientales/efectos adversos , Micronúcleos con Defecto Cromosómico/patología , Neoplasias de la Vejiga Urinaria/inducido químicamente , Neoplasias de la Vejiga Urinaria/patología , Contaminación Química del Agua/efectos adversos , Adulto , Anciano , Arsénico/orina , Estudios de Casos y Controles , Chile , Estudios Transversales , Humanos , Hibridación Fluorescente in Situ , Masculino , Pruebas de Micronúcleos , Persona de Mediana Edad , PrevalenciaRESUMEN
Inorganic arsenic (In-As), an occupational and environmental human carcinogen, undergoes biomethylation to monomethylarsonate (MMA) and dimethylarsinate (DMA). It has been proposed that saturation of methylation capacity at high exposure levels may lead to a threshold for the carcinogenicity of In-As. The relative distribution of urinary In-As, MMA, and DMA is used as a measure of human methylation capacity. The most common pathway for elevated environmental exposure to In-As worldwide is through drinking water. We conducted a biomarker study in northern Chile of a population chronically exposed to water naturally contaminated with high arsenic content (600 micrograms/l). In this paper we present the results of a prospective follow-up of 73 exposed individuals, who were provided with water of lower arsenic content (45 micrograms/l) for 2 months. The proportions of In-As, MMA, and DMA in urine were compared before and after intervention, and the effect of other factors on the distribution of arsenic metabolites was also analyzed. The findings of this study indicate that the decrease in arsenic exposure was associated with a small decrease in the percent In-As in urine (from 17.8% to 14.6%) and in the MMA/DMA ratio (from 0.23 to 0.18). Other factors such as smoking, gender, age, years of residence, and ethnicity were associated mainly with changes in the MMA/DMA ratio, with smoking having the strongest effect. Nevertheless, the factors investigated accounted for only about 20% of the large interindividual variability observed. Genetic polymorphisms in As-methylating enzymes and other co-factors are likely to contribute to some of the unexplained variation. The changes observed in the percent In-As and in the MMA/DMA ratio do not support an exposure-based threshold for arsenic methylation in humans.
Asunto(s)
Arsénico/análisis , Arsénico/farmacocinética , Contaminantes del Agua/análisis , Abastecimiento de Agua/análisis , Adulto , Anciano , Anciano de 80 o más Años , Arsénico/orina , Arsenicales/orina , Biotransformación , Ácido Cacodílico/orina , Chile , Femenino , Humanos , Masculino , Metilación , Persona de Mediana EdadRESUMEN
Methylation is considered the detoxification pathway for inorganic arsenic (InAs), an established human carcinogen. Urinary speciation analysis is used to assess the distribution of metabolites [monomethylarsonate (MMA), dimethylarsinate (DMA), and unmethylated arsenic (InAs)], as indicators of methylation capacity. We conducted a large biomarker study in northern Chile of a population chronically exposed to high levels of arsenic in drinking water. We report the results of the methylation study, which focused on the effects of exposure and other variables on the percent InAs, MMA, DMA, and the ratio of MMA to DMA in urine. The study consisted of 122 people in a town with arsenic water levels around 600 micrograms/l and 98 participants in a neighboring town with arsenic levels in water of about 15 micrograms/l. The corresponding mean urinary arsenic levels were 580 micrograms/l and 60 micrograms/l, of which 18.4% and 14.9% were InAs, respectively. The main differences were found for MMA:DMA; exposure, smoking, and being male were associated with higher MMA:DMA, while longer residence, Atacameño ethnicity, and being female were associated with lower MMA:DMA. Together, these variables explained about 30% of the variability in MMA:DMA. Overall, there was no evidence of a threshold for methylation capacity, even at very high exposures, and the interindividual differences were within a much wider range than those attributed to the variables investigated. The differences in percent InAs were small and within the ranges of other studies of background exposure levels. The biological significance of MMA:DMA, which was more than 1.5 times greater in the exposed group, and its relationship to sex, length of exposure, and ethnicity need further investigation because its relevance to health risk is not clear.
Asunto(s)
Arsénico/análisis , Arsénico/metabolismo , Arsenicales/orina , Ácido Cacodílico/orina , Contaminantes del Agua/análisis , Abastecimiento de Agua/análisis , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Chile , Exposición a Riesgos Ambientales , Femenino , Humanos , Masculino , Metilación , Persona de Mediana Edad , Análisis de RegresiónRESUMEN
Inorganic arsenic (In-As) is known to be a human carcinogen, causing lung cancer by inhalation and skin cancer by ingestion. Ecologic studies in Taiwan have found a dose-response relation between ingestion of In-As from drinking water and bladder cancer, but questions have been raised concerning the validity and generalizability of the findings. Several areas of Argentina have had high exposures to arsenic from naturally contaminated drinking water, particularly the eastern region of the province of Córdoba. In this study, we investigated bladder cancer mortality for the years 1986-1991 in Córdoba's 26 counties, using rates for all of Argentina as the standard for comparison. Bladder cancer standardized mortality ratios (SMRs) were consistently higher in counties with documented arsenic exposure. We grouped counties into low-, medium-, and high-exposure categories; the corresponding SMRs [with 95% confidence intervals (CI)] were 0.80 (95% CI = 0.66-0.96), 1.42 (95% CI = 1.14-1.74), and 2.14 (95% CI = 1.78-2.53) for men, and 1.21 (95% CI = 0.85-1.64), 1.58 (95% CI = 1.01-2.35), and 1.82 (95% CI = 1.19-2.64) for women. The clear trends found in a population with different genetic composition and a high-protein diet support the findings in Taiwan.