It has been suggested that the indigenous Atacameño people in Northern Chile might be protected from the health effects of arsenic in drinking water because of many centuries of exposure. Here we report on the first intensive investigation of arsenic-induced skin lesions in this population. We selected 11 families (44 participants) from the village of Chiu Chiu, which is supplied with water containing between 750 and 800 microg/L inorganic arsenic. For comparison, 8 families (31 participants) were also selected from a village where the water contains approximately 10 microg/L inorganic arsenic. After being transported to the nearest city for blind assessment, participants were examined by four physicians with experience in studying arsenic-induced lesions. Four of the six men from the exposed village, who had been drinking the contaminated water for more than 20 years, were diagnosed with skin lesions due to arsenic, but none of the women had definite lesions. A 13-year-old girl had definite skin pigmentation changes due to arsenic, and a 19-year-old boy had both pigmentation changes and keratoses on the palms of his hands and the soles of his feet. Family interviews identified a wide range of fruits and vegetables consumed daily by the affected participants, as well as the weekly intake of red meat and chicken. However, the prevalence of skin lesions among men and children in the small population studied was similar to that reported with corresponding arsenic drinking water concentrations in both Taiwan and West Bengal, India--populations in which extensive malnutrition has been thought to increase susceptibility.

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.

A previous case-control study which utilised the occupational information available on the New Zealand Cancer Registry found an increased risk of multiple myeloma in agricultural workers consistent with previous findings in the United States. The findings are now presented for the second phase of the study which involved interviewing 76 cases of multiple myeloma (who had been included in the previous study) together with 315 controls with other types of cancer. The previous finding on an excess of farmers in the case group was confirmed by the interview data (odds ratio = 1.7, 95% confidence limits 1.0-2.9, P = 0.04). There were no significant differences between cases and controls regarding potential exposure to phenoxy herbicides or chlorophenols. There were also no significant differences regarding activities involving potential exposure to other agricultural chemicals, although the odds ratio for fencing work, which may involve exposure to arsenic and sodium pentachlorophenate, was 1.6 (95% confidence limits 0.9-2.7, P = 0.11). The odds ratios were significantly elevated for sheep farming (odds ratio = 1.9, 95% confidence limits 1.0-3.6, P = 0.04) and exposure to beef cattle (odds ratio = 1.7, 95% confidence limits 1.0-2.9, P = 0.05). The odds ratio was also elevated for persons reporting a history of hay fever (odds ratio = 1.9, 95% confidence limits 1.0-3.5, P = 0.05). Overall, these findings suggest that the search for the causes of elevated mortality in farmers from multiple myeloma should be directed to potential causes other than pesticide exposure.

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.

San Francisco bus drivers have an increased prevalence of hypertension. This study examined relationships between blood lead concentration and blood pressure in 342 drivers. The analysis reported in this study was limited to subjects not on treatment for hypertension (n = 288). Systolic and diastolic pressures varied from 102 to 173 mm Hg and from 61 to 105 mm Hg, respectively. The blood lead concentration varied from 2 to 15 micrograms/dL. The relationship between blood pressure and the logarithm of blood lead concentration was examined using multiple regression analysis. Covariates included age, body mass index, sex, race, and caffeine intake. The largest regression coefficient relating systolic blood pressure and blood lead concentration was 1.8 mm Hg/ln (micrograms/dL) [90% C. I., -1.6, 5.3]. The coefficient for diastolic blood pressure was 2.5 mm Hg/ln (micrograms/dL) [90% C. I., 0.1, 4.9]. These findings suggest effects of lead exposure at lower blood lead concentrations than those concentrations that have previously been linked with increases in blood pressure.

Ingestion of arsenic, both from water supplies and medicinal preparations, is known to cause skin cancer. The evidence assessed here indicates that arsenic can also cause liver, lung, kidney, and bladder cancer and that the population cancer risks due to arsenic in U.S. water supplies may be comparable to those from environmental tobacco smoke and radon in homes. Large population studies in an area of Taiwan with high arsenic levels in well water (170-800 micrograms/L) were used to establish dose-response relationships between cancer risks and the concentration of inorganic arsenic naturally present in water supplies. It was estimated that at the current EPA standard of 50 micrograms/L, the lifetime risk of dying from cancer of the liver, lung, kidney, or bladder from drinking 1 L/day of water could be as high as 13 per 1000 persons. It has been estimated that more than 350,000 people in the United States may be supplied with water containing more than 50 micrograms/L arsenic, and more than 2.5 million people may be supplied with water with levels above 25 micrograms/L. For average arsenic levels and water consumption patterns in the United States, the risk estimate was around 1/1000. Although further research is needed to validate these findings, measures to reduce arsenic levels in water supplies should be considered.

A multicenter observational study was conducted on early lactation Holstein cows (n = 261) from 32 herds from 3 regions (Australia, AU; California, CA; and Canada, CAN) to characterize their risk of acidosis into 3 groups (high, medium, or low) using a discriminant analysis model previously developed. Diets ranged from pasture supplemented with concentrates to total mixed ration (nonfiber carbohydrates = 17 to 47 and neutral detergent fiber = 27 to 58% of dry matter). Rumen fluid samples were collected <3 h after feeding and analyzed for pH, and ammonia, d- and l-lactate, and volatile fatty acid (VFA) concentrations. Eigenvectors were produced using cluster and discriminant analysis from a combination of rumen pH, and ammonia, d-lactate, and individual VFA concentrations and were used to calculate the probability of the risk of ruminal acidosis based on proximity to the centroid of 3 clusters. Bacterial 16S ribosomal DNA sequence data were analyzed to characterize bacteria. Individual cow milk volume, fat, protein, and somatic cell count values were obtained from the closest herd test to the rumen sampling date (median = 1 d before rumen sampling). Mixed model analyses were performed on the markers of rumen fermentation, production characteristics, and the probability of acidosis. A total of 26.1% of the cows were classified as high risk for acidosis, 26.8% as medium risk, and 47.1% as low risk. Acidosis risk differed among regions with AU (37.2%) and CA (39.2%) having similar prevalence of high-risk cows and CAN only 5.2%. The high-risk group had rumen phyla, fermentation, and production characteristics consistent with a model of acidosis that reflected a rapid rate of carbohydrate fermentation. Namely, acetate to propionate ratio (1.98 ± 0.11), concentrations of valerate (2.93 ± 0.14 mM), milk fat to protein ratio (1.11 ± 0.047), and a positive association with abundance of phylum Firmicutes. The medium-risk group contains cows that may be inappetant or that had not eaten recently or were in recovery from acidosis. The low-risk group may represent cattle that are well fed with a stable rumen and a slower rumen fermentation of carbohydrates. The high risk for acidosis group had lower diversity of bacteria than the other groups, whereas CAN had a greater diversity than AU and CA. Rumen fermentation profile, abundance of ruminal bacterial phyla, and production characteristics of early lactation dairy cattle from 3 regions were successfully categorized in 3 different acidosis risk states, with characteristics differing between acidosis risk groups. The prevalence of acidosis risk also differed between regions.