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Discharge of groundwater contaminant plumes has created elevated concentrations of Sr in some aquatic sediments at Chalk River Laboratories. Tree swallows (Tachycenita bicolor) feed and supply their nestlings almost exclusively with airborne insects that developed as larvae in aquatic sediments. To monitor the uptake and test for potential detriment due to Sr in a terrestrial animal, we measured the gross beta concentrations in the bone of 12-d-old tree swallow nestlings in areas having sediments with elevated levels of gross beta (Sr and Y) and in several control areas where sediment gross beta was primarily due to naturally occurring K. Nesting behavior and reproductive success of the tree swallows were similar regardless of the gross beta concentrations in sediments near their nest boxes. Radiation can damage DNA and cause micronuclei to form in cells, so we examined the frequency of micronuclei in erythrocytes of nestlings. The formation of micronuclei in the erythrocytes of the nestlings was also similar wherever nestlings were analyzed. The results revealed no significant increases even near sediments with the highest gross beta levels. At Perch Lake, where Chalk River Laboratories has a large area of Sr-contaminated sediments, the bones of 12-d-old nestlings contained gross beta concentrations as high as 29 Bq g. This would produce a skeletal dose rate of 9 μGy h, which is one-fourth of the threshold dose rate of 40 μGy h, above which detriment could occur. Failing to find any indication of detriment in the field study, we irradiated wild eggs in the lab and returned them to their nest for natural incubation, hatching, and feeding by the parents. There was an increase in formation of micronuclei following a dose of 3.2 Gy, and the other results were consistent with existing literature.

Context: The City of Flint was already distressed because of decades of financial decline when an estimated 140 000 individuals were exposed to lead and other contaminants in drinking water. In April 2014, Flint's drinking water source was changed from Great Lakes' Lake Huron (which was provided by the Detroit Water and Sewerage Department) to the Flint River without necessary corrosion control treatment to prevent lead release from pipes and plumbing. Lead exposure can damage children's brains and nervous systems, lead to slow growth and development, and result in learning, behavior, hearing, and speech problems. After the involvement of concerned residents and independent researchers, Flint was reconnected to the Detroit water system on October 16, 2015. A federal emergency was declared in January 2016., Program: The Centers for Disease Control and Prevention provided assistance and support for response and recovery efforts including coordinating effective health messaging; assessing lead exposure; providing guidance on blood lead screening protocols; and identifying and linking community members to appropriate follow-up services.In response to the crisis in Flint, Congress funded the Centers for Disease Control and Prevention to establish a federal advisory committee; enhance Childhood Lead Poisoning Prevention Program activities; and support a voluntary Flint lead exposure registry. The registry, funded through a grant to Michigan State University, is designed to identify eligible participants and ensure robust registry data; monitor health, child development, service utilization, and ongoing lead exposure; improve service delivery to lead-exposed individuals; and coordinate with other community and federally funded programs in Flint. The registry is also collaborating to make Flint "lead-free" and to share best practices with other communities., Discussion: The Flint water crisis highlights the need for improved risk communication strategies, and environmental health infrastructure, enhanced surveillance, and primary prevention to identify and respond to environmental threats to the public's health. Collecting data is important to facilitate action and decision making to prevent lead poisoning. Partnerships can help guide innovative strategies for primary lead prevention, raise awareness, extend outreach and communication efforts, and promote a shared sense of ownership.

Objective: The aim of this study was to characterize environmental exposure from Deepwater Horizon oil spill among pre-K to fourth-grade children from six schools in Mobile County, Alabama., Methods: A mail-in survey administered 11 months post-oil spill to children's parents/caregivers elicited information on exposure-related activities. Descriptive and multivariable analyses were performed., Results: Overall, 180 children (coastal schools, 90; inland schools, 90) completed the survey. During the post-oil spill period, children in coastal schools were less likely to reduce their exposure-related activities, including fishing; eating and selling caught fish; visiting beaches; and parental participation in cleanup activities, than children in inland schools. Particularly, fishing and eating caught fish were significantly associated with the coastal group (odds ratio = 2.28; 95% confidence interval = 1.54 to 3.36)., Conclusion: Proximity to the shoreline may serve as an indicator for potential exposure in oil spills among vulnerable populations including children.

Objective: Because of emerging evidence that early-life exposure to the solvent tetrachloroethylene (PCE) has long-lasting neurological consequences, we examined the risk of unintentional head injuries following prenatal and childhood exposure to PCE-contaminated drinking water., Methods: Participants provided information on head injuries and other relevant characteristics in a self-administered questionnaire. Exposure to PCE was modeled using a leaching and transport algorithm set in water system modeling software., Results: We did not observe any evidence of an increased risk of any type of head injury among exposed participants., Conclusions: PCE is a widespread water pollutant. Thus, documenting possible health effects of early-life exposure is vital for ensuring that drinking water regulations adequately protect vulnerable populations.

Context: Environmental Public Health Tracking (EPHT) tracks the occurrence and magnitude of environmental hazards and associated adverse health effects over time. The EPHT program has formally expanded its scope to include finished drinking water quality., Objectives: Our objective was to describe the features, strengths, and limitations of using finished drinking water quality data from community water systems (CWSs) for EPHT applications, focusing on atrazine and nitrogen compounds in 8 Midwestern states., Methods: Water quality data were acquired after meeting with state partners and reviewed and merged for analysis., Results: Data and the coding of variables, particularly with respect to censored results (nondetects), were not standardized between states. Monitoring frequency varied between CWSs and between atrazine and nitrates, but this was in line with regulatory requirements. Cumulative distributions of all contaminants were not the same in all states (Peto-Prentice test P < .001). Atrazine results were highly censored in all states (76.0%-99.3%); higher concentrations were associated with increased measurement frequency and surface water as the CWS source water type. Nitrate results showed substantial state-to-state variability in censoring (20.5%-100%) and in associations between concentrations and the CWS source water type., Conclusions: Statistical analyses of these data are challenging due to high rates of censoring and uncertainty about the appropriateness of parametric assumptions for time-series data. Although monitoring frequency was consistent with regulations, the magnitude of time gaps coupled with uncertainty about CWS service areas may limit linkage with health outcome data.

Objective: To evaluate the relationship between arsenic exposure and oral cavity lesions among an arsenic-exposed population in Bangladesh., Methods: We carried out an analysis utilizing the baseline data of the Health Effects of Arsenic Exposure Longitudinal Study, which is an ongoing population-based cohort study to investigate health outcomes associated with arsenic exposure via drinking water in Araihazar, Bangladesh. We used multinomial regression models to estimate the risk of oral cavity lesions., Results: Participants with high urinary arsenic levels (286.1 to 5000.0 μg/g) were more likely to develop arsenical lesions of the gums (multinomial odds ratio = 2.90; 95% confidence interval, 1.11 to 7.54), and tongue (multinomial odds ratio = 2.79; 95% confidence interval, 1.51 to 5.15), compared with those with urinary arsenic levels of 7.0 to 134.0 μg/g., Conclusions: Higher level of arsenic exposure was positively associated with increased arsenical lesions of the gums and tongue.

Objective: To evaluate associations between maternal drinking water perchlorate exposure during pregnancy and newborn thyroid hormone levels., Methods: Elevation in thyroid stimulating hormone (TSH), which may reflect reduced thyroxin concentration, was assessed in 497,458 newborns in California in 1998. A total of 800 perchlorate water measurements were used to classify California communities as exposed (>5 μg/L) or unexposed. Results were stratified by age at TSH collection because of the normal postbirth TSH surge, and because water sources and perchlorate exposure can change soon after birth., Results: In TSH samples collected within 24 hours of birth, the odds ratio for a TSH greater than 25 μU/mL in exposed communities was 1.53 (P < 0.0001). After 24 hours, the odds ratio for a TSH more than the 95th percentile was 1.27 (P < 0.0001)., Conclusion: These findings suggest that perchlorate is associated with increased neonatal TSH levels.

Background: Laboratory evidence suggests tap water disinfection by-products (DBPs) could have an effect very early in pregnancy, typically before clinical detectability. Undetected early losses would be expected to increase the reported number of cycles to clinical pregnancy., Methods: We investigated the association between specific DBPs (trihalomethanes, haloacetic acids, brominated-trihalomethanes, brominated-haloacetic acids, total organic halides, and bromodichloromethane) and time to pregnancy among women who enrolled in a study of drinking water and reproductive outcomes. We quantified exposure to DBPs through concentrations in tap water, quantity ingested through drinking, quantity inhaled or absorbed while showering or bathing, and total integrated exposure. The effect of DBPs on time to pregnancy was estimated using a discrete time hazard model., Results: Overall, we found no evidence of an increased time to pregnancy among women who were exposed to higher levels of DBPs. A modestly decreased time to pregnancy (ie, increased fecundability) was seen among those exposed to the highest level of ingested DBPs, but not for tap water concentration, the amount absorbed while showering or bathing, or the integrated exposure., Conclusions: Our findings extend those of a recently published study suggesting a lack of association between DBPs and pregnancy loss.

Objective: The purpose of this study was to examine the association between arsenic exposure and anemia, based on blood hemoglobin concentration., Methods: Hemoglobin measures, skin lesions, arsenic exposure, and nutritional and demographic information were collected from 1954 Bangladeshi participants in the Health Effects of Arsenic Longitudinal Study. We used general linear modeling to assess the association between arsenic exposure and hemoglobin concentration, examining men and women separately., Results: Arsenic exposure (urinary arsenic >200 microg/L) was negatively associated with hemoglobin among all men and among women with hemoglobin <10 d/L. Other predictors of anemia in men and women included older age, lower body mass index, and low intake of iron. Among women, the use of contraceptives predicted higher hemoglobin., Conclusions: The study suggests an association between high arsenic exposure and anemia in Bangladesh.

Background: Children may be at higher risk than adults from pesticide exposure, due to their rapidly developing physiology, unique behavioral patterns, and interactions with the physical environment. This preliminary study conducted in Ecuador examines the association between household and environmental risk factors for pesticide exposure and neurobehavioral development., Methods: We collected data over 6 months in the rural highland region of Cayambe, Ecuador (2003-2004). Children age 24-61 months residing in 3 communities were assessed with the Ages and Stages Questionnaire and the Visual Motor Integration Test. We gathered information on maternal health and work characteristics, the home and community environment, and child characteristics. Growth measurements and a hemoglobin finger-prick blood test were obtained. Multiple linear regression analyses were conducted., Results: Current maternal employment in the flower industry was associated with better developmental scores. Longer hours playing outdoors were associated with lower gross and fine motor and problem solving skills. Children who played with irrigation water scored lower on fine motor skills (8% decrease; 95% confidence interval = -9.31 to -0.53), problem-solving skills (7% decrease; -8.40 to -0.39), and Visual Motor Integration test scores (3% decrease; -12.00 to 1.08)., Conclusions: These results suggest that certain environmental risk factors for exposure to pesticides may affect child development, with contact with irrigation water of particular concern. However, the relationships between these risk factors and social characteristics are complex, as corporate agriculture may increase risk through pesticide exposure and environmental contamination, while indirectly promoting healthy development by providing health care, relatively higher salaries, and daycare options.

Background: Very little evidence exists concerning the possible impairment of children's intellectual function in relation to arsenic exposure in utero and during childhood., Methods: We conducted a cross-sectional study among 351 children age 5 to 15 years who were selected from a source population of 7683 people in West Bengal, India, in 2001-2003. Intellectual function was assessed with 6 subtests from the Wechsler Intelligence Scale for Children as well as with the Total Sentence Recall test, the Colored Progressive Matrices test, and a pegboard test. Arsenic in urine and lifetime water sources (including during the pregnancy period) were assessed using measurements of samples from 409 wells. The test scores were analyzed with linear regression analyses based on the method of generalized estimating equations incorporating relevant covariates., Results: Stratifying urinary arsenic concentrations into tertiles, we found associations between arsenic and reductions in the adjusted scores of the vocabulary test (0, -0.14, -0.28; P for trend = 0.02), the object assembly test (0, -0.16, -0.24; P for trend = 0.03), and the picture completion test (0, -0.15, -0.26; P for trend = 0.02). These findings correspond to relative declines of 12% (95% confidence interval =0.4% to 24%) in the vocabulary test, 21% (-0.8% to 42%) in the object assembly test, and of 13% (0.3% to 24%) in the picture completion test in the upper urinary arsenic tertile. However, we did not find evidence of an association between test results and arsenic water concentrations during pregnancy or childhood., Conclusions: Current arsenic concentrations in urine, which reflect all sources of recent exposure, including water and food, were associated with small decrements in intellectual testing in school-aged children in West Bengal. We did not see associations between long-term water arsenic concentrations and intellectual function.

Introduction: Nitrate and nitrite are precursors in the in vivo formation of N-nitroso compounds, potent animal carcinogens., Methods: We conducted a population-based case-control study of non-Hodgkin lymphoma (NHL) in 1998 to 2000 in Iowa, Detroit, Seattle, and Los Angeles. Because nitrate levels were elevated in many drinking water supplies in Iowa, but not in the other study centers, we evaluated water nitrate levels and risk of NHL in Iowa only. Monitoring data for public supplies were linked to water source histories from 1960 onward. Nitrate was measured at interview homes with private wells. We limited most analyses to those with nitrate estimates for > 70% of their person-years since 1960 (181 cases, 142 controls). For those in the diet arm of the study (458 cases, 383 controls from 4 centers) and for Iowa participants in both the diet and drinking water analyses, we estimated dietary nitrate and nitrite intake using a 117-item food-frequency questionnaire that included foods high in nitrate and nitrite. Odds ratios and 95% confidence intervals were calculated using logistic regression, adjusting for the study matching factors, education, and caloric intake (diet analyses only)., Results: We found no overall association with the highest quartile of average drinking water nitrate (> 2.90 mg/L nitrate-N: odds ratios = 1.2; 95% confidence interval = 0.6-2.2) or with years > or = 5 mg/L (10+ years: 1.4; 0.7-2.9). We observed no evidence of an interaction between drinking water nitrate exposure and either vitamin C or red meat intake, an inhibitor and precursor, respectively, of N-nitroso compound formation. Among those in the diet arm, dietary nitrate was inversely associated with risk of NHL (highest quartile: 0.54; 0.34-0.86). Dietary nitrite intake was associated with increasing risk (highest quartile: 3.1; 1.7-5.5) largely due to intakes of bread and cereal sources of nitrite., Conclusion: Average drinking water nitrate levels below 3 mg/L were not associated with NHL risk. Our study had limited power to evaluate higher levels that deserve further study.

Objective: Arsenic is associated with numerous health effects. We investigated the association between arsenic exposure from drinking water and anemia during pregnancy., Methods: We conducted a prospective cohort pregnancy study in two Chilean cities with contrasting drinking water arsenic levels: 40 microg/L versus <1 microg/L. This analysis included 810 women who gave birth to live, singleton infants and had at least one hemoglobin determination during pregnancy., Results: Arsenic exposed women were more likely to be anemic during pregnancy after adjusting for other factors. Furthermore, as pregnancy progressed, the prevalence of anemia rose more sharply among those in the exposed versus unexposed city: 49% versus 17%., Conclusion: This study suggests an association between moderate arsenic in drinking water and anemia during pregnancy. Further research is needed to identify the specific types of anemia underlying the association.

The authors report assessment of abnormal ocular movements in three patients after organoarsenic poisoning from diphenylarsinic acid. The characteristic and principal sign is upward gaze-evoked nystagmus. Moreover, vertical gaze holding impairment was shown by electronystagmography on direct current recording.

Objective: Long-term arsenic exposure has been reported to associated with prevalence, incidence, and mortality of diabetes mellitus (DM). A tap water supply system was implemented in the early 1960s in the blackfoot disease (BFD) endemic areas. The objective of this study is to examine whether DM mortality decreased after the improvement of drinking water supply system through elimination of arsenic exposure from artesian well water., Methods: Standardized mortality ratios (SMRs) for DM were calculated for the BFD endemic area for the years 1971-2000., Results: The study results show that mortality from DM declined in females (but not in males) gradually after the improvement of drinking water supply system., Conclusions: Based on the reversibility criterion, the association between arsenic exposure and DM is likely to be casual for females but not in males.

Background: Community concerns about a potential excess of multiple sclerosis (MS) prompted this study., Objective: To determine the period prevalence of MS in a community bordering a closed oil refinery and a control community., Methods: Cases seen by a neurologist during 1998 to 2001 were obtained from area neurologists and hospital discharge data. Population data were obtained from the year 2000 US Census. Patient data were abstracted by a trained abstractor onto a standardized report form. A consulting neurologist reviewed the form and made a final diagnosis using the Poser criteria plus the category of presumed. Age-adjusted prevalence rates and rates of agreement were calculated., Results: The direct age-adjusted period prevalence for both sexes and all races for the entire study area was 113 per 100,000 (95% CI = 93 to 136). For white subjects only, the prevalence was 123 per 100,000 (95% CI = 102 to 147). With use of an indirect method of age adjustment, the number of observed cases in the community bordering the refinery was similar to the number of cases expected (standardized morbidity ratio = 130.8, 95% CI = 62.3 to 199.3), based on rates from the comparison area. The agreement between the treating neurologist (for definite plus probable cases) and the consulting neurologist (for definite plus probable plus presumed cases) was good (kappa = 0.5733)., Conclusions: The prevalence of multiple sclerosis (MS) for this area was generally consistent with prevalence estimates calculated in previous studies in other areas. No significant excess was seen in the exposed area. MS was more prevalent in females than in males. The overall agreement between the consulting and treating neurologist was good.

The objectives of this study were to evaluate whether there were higher rates of primary congenital hypothyroidism (PCH) or elevated concentrations of thyroid-stimulating hormone (TSH) in a community where perchlorate was detected in groundwater wells. The adjusted PCH prevalence ratio and 95% confidence interval (CI) comparing the study community to San Bernardino and Riverside counties combined was 0.45 (95% CI=0.06-1.64). The odds ratios for elevated TSH concentration were 1.24 (95% CI=0.89-1.68) among all newborns screened and 0.69 (95% CI=0.27-1.45) for newborns whose age at screening was 18 hours or greater. Age of the newborn at time of screening was the most important predictor of the TSH level. These findings suggest that residence in a community with potential perchlorate exposure has not impacted PCH rates or newborn thyroid function.

Background: Concerns about potential health effects of trihalomethanes (THMs) have prompted investigations on whether infants whose mothers were periconceptionally exposed to drinking water containing THMs are at greater risk of congenital malformations., Methods: We used two large case-control maternal interview studies that were conducted among California deliveries from 1987 through 1991. One study comprised 538 infants/fetuses with neural tube defects (NTDs) and 539 nonmalformed control infants. The second study included an additional 265 infants with NTDs, 207 infants with conotruncal heart defects, 409 infants with orofacial clefts, and 481 control infants. Expert personnel from municipal water companies estimated THM levels for a particular residence and specific periconceptional time period using quarterly monitoring measurements. Estimates were also made for four individual THM levels and for the total THM level., Results: NTD risk in the first study was inversely associated with total THM exposure. Although the second study did not show the same inverse relationship for NTDs, there were no positive associations of NTDs or the other malformations with total THM as estimated from continuous models. Elevated risks were observed for the lowest category of exposure (1-24 ppb), but risks were either not substantially elevated or were imprecise for higher exposure levels. Thus no evidence was observed for an exposure-response relation., Conclusions: Our results do not provide a clear pattern of association between THM exposure and risks of specific congenital malformations. Imprecise exposure measures coupled with a lack of information about other possible sources of THM exposure may have caused associations to be underestimated.

Background: Nitrate is a precursor compound in the formation of N-nitroso compounds, most of which are potent animal carcinogens. N-nitroso compounds and their precursors have not been extensively evaluated as bladder cancer risk factors., Methods: We conducted a population-based case-control study of bladder cancer in Iowa. Cases were men and women newly diagnosed with bladder cancer in 1986-1989. Nitrate data for Iowa public water supplies were sparse before the 1960s. To reduce misclassification by unknown nitrate levels, we included only those who used public supplies with nitrate data for 70% or more of their person-years since 1960 (808 cases, 1259 controls)., Results: Among controls, the median average nitrate level for their Iowa residences with public water supplies was 1.3 mg/liter nitrate-nitrogen (interquartile range = 0.6-3.0). After adjustment for confounders, we found no increased risk of bladder cancer with increasing average nitrate levels in drinking water; the highest quartile odds ratio for women was 0.8 (95% confidence interval = 0.4-0.8), and for men 0.5 (0.4-0.8). We observed no association among those with high water nitrate exposure (>median) and low (

Potassium perchlorate has been used at various times during the last 50 years to treat hyperthyroidism. Since World War II ammonium perchlorate has been used as a propellant for rockets. In 1997, the assay sensitivity for perchlorate in water was improved from 0.4 mg/L (ppm) to 4 microg/L (ppb). As a result, public water supplies in Southern California were found to contain perchlorate ions in the range of 5 to 8 ppb, and those in Southern Nevada were found to contain 5 to 24 ppb. Research programs have been developed to assess the safety or risk from these exposures and to assist state and regulatory agencies in setting a reasonable safe level for perchlorate in drinking water. This report reviews the evidence on the human health effects of perchlorate exposure. Perchlorate is a competitive inhibitor of iodine uptake. All of its pharmacologic effects at current therapeutic levels or lower are associated with inhibition of the sodium-iodide symporter (NIS) on the thyroid follicular cell membrane. A review of the medical and occupational studies has been undertaken to identify perchlorate exposure levels at which thyroid hormone levels may be reduced or thyrotropin levels increased. This exposure level may begin in the 35 to 100 mg/d range. Volunteer studies have been designed to determine the exposure levels at which perchlorate begins to affect iodine uptake in humans. Such effects may begin at levels of approximately 1 mg/d. Environmental studies have assessed the thyroidal health of newborns and adults at current environmental exposures to perchlorate and have concluded that the present levels appear to be safe. Whereas additional studies are underway both in laboratory animals and in the field, it appears that a safe level can be established for perchlorate in water and that regulatory agencies and others are now trying to determine that level.

Agricultural activity on Prince Edward Island poses a potential hazard to groundwater, which is the sole source of drinking water on the island. This study investigates the potential impact of groundwater nitrate exposure on prematurity and intrauterine growth restriction on Prince Edward Island. A total of 210 intrauterine growth restriction cases, 336 premature births, and 4098 controls were abstracted from a database of all Island births. An ecological measure of groundwater nitrate level was used to gauge potential exposure to agriculturally contaminated drinking water. The higher nitrate exposure categories were positively associated with intrauterine growth restriction and prematurity, and significant dose-response trends were seen, even after adjustment for several important covariates. Nevertheless, these risks must be interpreted cautiously because of the ecological nature of this exposure metric. An investigation using nitrate levels for individual study subjects is needed to confirm this association.

We conducted a population-based case-control study to evaluate the relation between exposure to drinking water contaminants (total and specific trihalomethanes and certain metals and nitrates) and childhood acute lymphoblastic leukemia. We compared 491 cases 0-9 years of age with 491 controls. We developed a municipality-exposure matrix based on municipal and provincial historical data, a tapwater survey in 227 homes, and information about residential history. We used average level of exposure and cumulative average over the period as exposure indices, and we measured risk for the pregnancy period as well as for the postnatal period. We show that risks were generally not increased for the prenatal period nor with average levels of exposure. Postnatal cumulative exposure for total trihalomethanes at above the 95th percentile of the distribution for cases and controls was associated with an odds ratio of 1.54 (95% confidence interval = 0.78-3.03); for that same period, risk associated with exposure to chloroform was increased (odds ratio = 1.63; 95% confidence interval = 0.84-3.19) as well as that for exposure to zinc (odds ratio = 2.48; 95% confidence interval = 0.99-6.24). Risks were also increased for exposure to cadmium and arsenic, but not for other metals nor for nitrates.

Cities in northern Chile had arsenic concentrations of 860 microg/liter in drinking water in the period 1958-1970. Concentrations have since been reduced to 40 microg/liter. We investigated the relation between lung cancer and arsenic in drinking water in northern Chile in a case-control study involving patients diagnosed with lung cancer between 1994 and 1996 and frequency-matched hospital controls. The study identified 152 lung cancer cases and 419 controls. Participants were interviewed regarding drinking water sources, cigarette smoking, and other variables. Logistic regression analysis revealed a clear trend in lung cancer odds ratios and 95% confidence intervals (CIs) with increasing concentration of arsenic in drinking water, as follows: 1, 1.6 (95% CI = 0.5-5.3), 3.9 (95% CI = 1.2-12.3), 5.2 (95% CI = 2.3-11.7), and 8.9 (95% CI = 4.0-19.6), for arsenic concentrations ranging from less than 10 microg/liter to a 65-year average concentration of 200-400 microg/liter. There was evidence of synergy between cigarette smoking and ingestion of arsenic in drinking water; the odds ratio for lung cancer was 32.0 (95% CI = 7.2-198.0) among smokers exposed to more than 200 microg/liter of arsenic in drinking water (lifetime average) compared with nonsmokers exposed to less than 50 microg/liter. This study provides strong evidence that ingestion of inorganic arsenic is associated with human lung cancer.

The Colorado River below Lake Mead, which supplies drinking water for approximately 20,000,000 people, is contaminated by ammonium perchlorate. We identified populations who were exposed and unexposed to perchlorate-contaminated drinking water and compared median newborn thyroid-stimulating hormone (TSH) levels after adjusting for age in days at measurement and for race/ethnicity. Median newborn TSH levels in a city whose drinking water supply was 100% perchlorate-contaminated water from the Colorado River below Lake Mead were significantly higher than those in a city totally supplied with non-perchlorate-contaminated drinking water, even after adjusting for factors known or suspected to elevate newborn TSH levels. This ecological study demonstrates a statistically significant association between perchlorate exposure and newborn TSH levels. It suggests that even low-level perchlorate contamination of drinking water may be associated with adverse health effects in neonates and highlights the need for both further study and control of human low-level perchlorate exposure.

Wildlife studies suggest that consumption of contaminated fish from the Great Lakes may expose humans to polychlorinated biphenyls and persistent chlorinated pesticides. To assess whether time to pregnancy or fecundability is affected, we conducted a telephone survey in 1993 with female members of the New York State Angler Cohort Study who were considering pregnancy between 1991 and 1994 (N = 2,445). Among the 1,234 (50%) women who became pregnant, 895 (73%) had a known time to pregnancy. Upon enrollment into the cohort in 1991, both partners reported duration and frequency of Lake Ontario sport fish consumption. We estimated lifetime exposure to polychlorinated biphenyls from recent consumption and used a discrete-time analog of Cox proportional hazards analysis to estimate conditional fecundability ratios and 95% confidence intervals (CIs) for fish consumption among couples with complete exposure data who discontinued birth control to become pregnant (N = 575). Maternal consumption of fish for 3-6 years was associated with reduced fecundability (fecundability ratio = 0.75; 95% CI = 0.59-0.91), as was more than a monthly fish meal in 1991 (fecundability ratio = 0.73; 95% CI = 0.54-0.98). Our findings suggest that maternal but not paternal consumption of contaminated fish may reduce fecundability among couples attempting pregnancy.

Chlorination of drinking water that contains organic compounds leads to the formation of by-products, some of which have been shown to have mutagenic or carcinogenic effects. As yet, too little is known about the possible teratogenic effects on the human fetus. We linked the Norwegian waterwork registry, containing 1994 data on chlorination practice and color (an indicator for natural organic matter), with the Medical Birth Registry for 1993-1995. The proportion of the population exposed to chlorination and a weighted mean color number in drinking water was computed for each municipality. Among 141,077 births, 2,608 (1.8%) had birth defects. In a comparison between exposed (high color; chlorination) and reference groups (low color; no chlorination), the adjusted odds ratio was 1.14 (0.99-1.31) for any malformation, 1.26 (0.61-2.62) for neural tube defects, and 1.99 (1.10-3.57) for urinary tract defects. This study provides further evidence of the role of chlorination of humic water as a potential cause of birth defects, in a country with relatively low levels of chlorination byproducts.

Exposure during pregnancy to disinfection by-products in drinking water has been hypothesized to lead to several adverse reproductive outcomes. We performed a retrospective cohort study to examine the relation of trihalomethane exposure during the third trimester of pregnancy to low birthweight, term low birthweight, and preterm delivery. We matched Colorado birth certificates from January 1, 1990, through December 31, 1993, to historical water sample data with respect to time and location of maternal residence based on census block groups. After excluding births from all census block groups with no trihalomethane sample data and restricting to singleton white births with 28-42 weeks of completed gestation (>400 gm), we studied 1,893 livebirths within 28 census block groups. We found a weak association of trihalomethane exposure during the third trimester with low birthweight (odds ratio = 2.1 for the highest exposure level; 95% confidence interval = 1.0-4.8); a large increase in risk for term low birthweight at the highest level of exposure (odds ratio = 5.9; 95% confidence interval = 2.0-17.0); and no association between exposure and preterm delivery (odds ratio = 1.0 for the highest exposure level; 95% confidence interval = 0.3-2.8). The small number of adverse outcomes reduced the precision of risk estimates, but these data indicate a potentially important relation between third trimester exposure to trihalomethanes and retarded fetal growth.

Some studies indicate that chlorination by-products in drinking water may contribute slightly to breast cancer risk. This ecologic study describes the association between total trihalomethane levels in publicly supplied water and the incidence of female invasive breast cancer. We included 71 North Carolina water suppliers serving at least 10,000 customers in the summer of 1995 as the units of analysis. We estimated incidence rates using 6,462 cases who were either white or black and between 35 and 84 years old and were linked by zip codes to the water supplier. We treated ecologic measurements of age, income, education, urban status, and race as potential confounders. Total trihalomethane levels were not associated materially with breast cancer risk, adjusting for potential confounders. The rate ratio for 80.0 parts per billion (ppb) or more vs less than 40.0 ppb total trihalomethanes was 1.1 [95% confidence interval (CI) = 0.9-1.2]. When stratified by race, the observed association for the aforementioned total trihalomethane category was not very different in black women (rate ratio = 1.2; 95% CI = 0.8-1.8) than in white women (rate ratio = 1.1; 95% CI = 0.9-1.3). These ecologic data are compatible with trihalomethanes in drinking water being either unrelated or weakly related to breast cancer risk.

Trihalomethanes (chloroform, bromoform, bromodichloromethane, and chlorodibromomethane) are common contaminants of chlorinated drinking water. Although animal data indicate that these compounds may be reproductive toxicants, little information exists on their relation to spontaneous abortion in humans. We examined exposure to trihalomethanes and spontaneous abortion in a prospective study of 5,144 pregnant women in a prepaid health plan. Seventy-eight drinking water utilities provided concurrent trihalomethane sampling data. We calculated total trihalomethane levels by averaging all measurements taken by the subject's utility during her first trimester. We calculated exposures to individual trihalomethanes in an analogous manner. Women who drank > or = 5 glasses per day of cold tapwater containing > or = 75 micrograms per liter total trihalomethanes had an adjusted odds ratio (OR) of 1.8 for spontaneous abortion [95% confidence interval (CI) = 1.1-3.0]. Of the four individual trihalomethanes, only high bromodichloromethane exposure (consumption of > or = 5 glasses per day of cold tapwater containing > or = 18 micrograms per liter bromodichloromethane) was associated with spontaneous abortion both alone (adjusted OR = 2.0; 95% CI = 1.2-3.5) and after adjustment for the other trihalomethanes (adjusted OR = 3.0; 95% CI = 1.4-6.6).

In 1992, we published four retrospective studies, conducted primarily within a single California county, which found higher spontaneous abortion rates among women who drank more tapwater than bottled water in early pregnancy. The current prospective study extends that investigation to other water systems. Pregnant women from three regions in California were interviewed during their first trimester. Multivariate analyses modeled the amount and type of water consumed at 8 weeks' gestation in each region in relation to spontaneous abortion rate. In Region I, which was within the previous study area, the adjusted odds ratio (OR) comparing high (> or = 6 glasses per day) consumption of cold tapwater with none was 2.17 [95% confidence interval (CI) = 1.22-3.87]. Furthermore, when women with high cold tapwater and no bottled water consumption were compared with those with high bottled water and no cold tapwater consumption, the adjusted odds ratio was 4.58 (95% CI = 1.97-10.64). Conversely, women with high bottled water consumption and no tapwater had a reduced rate of spontaneous abortion compared with those drinking tapwater and no bottled water (adjusted OR = 0.22; 95% CI = 0.09-0.51). Neither tap nor bottled water consumption altered the risk of spontaneous abortion in Regions II and III. Although controlling for age, prior spontaneous abortion, race, gestational age at interview, and weight somewhat strengthened the association in Region I, the distribution of these confounders did not vary appreciably across regions. This study confirms the association between cold tapwater and spontaneous abortion first seen in this county in 1980. If causal, the agent(s) is not ubiquitous but is likely to have been present in Region I for some time.

The associations between arsenic ingestion and cancers of the bladder and kidney have been documented in Taiwan. To evaluate further such associations for urinary cancers of various cell types, we conducted an ecologic study encompassing 243 townships using cancer registry data of patients diagnosed between 1980 and 1987. We used the proportions of wells with various specified arsenic levels in each township as indicators of exposure and evaluated the effects of urbanization and smoking by an urbanization index and the number of cigarettes sold per capita. In both genders, we observed associations of high arsenic levels in drinking water with transitional cell carcinomas of the bladder, kidney, and ureter and all urethral cancers combined. We also observed such associations in adenocarcinomas of the bladder in males, but not in squamous cell carcinomas of the bladder or renal cell carcinomas or nephroblastomas of the kidney. There was also a positive association between the urbanization index and transitional cell carcinomas of the ureter in males. The number of cigarettes sold per capita was not a good predictor for urinary cancers. The results indicate that the carcinogenicity of arsenic may be cell type specific.

The increasing incidence of non-Hodgkin's lymphoma (NHL) in the United States is only partially explained by known risk factors. Nitrate is a contaminant of drinking water in many rural areas. We evaluated its association with NHL after accounting for dietary nitrate intake. For 156 cases and 527 controls who used Nebraska community supplies, average nitrate exposure was estimated from 1947 through 1979. Longterm consumption of community water with average nitrate levels in the highest quartile (> or = 4 mg per liter nitrate-nitrogen) was positively associated with risk [odds ratio (OR) = 2.0; 95% confidence interval (CI) = 1.1-3.6]. Dietary nitrate, which came mainly from vegetables, was not associated with NHL risk, after adjusting for vitamin C and carotene intakes. Persons with a lower intake of vitamin C were at slightly higher risk of developing NHL than persons whose daily intake was > or = 130 mg, for all levels of intake of drinking water nitrate; our findings were similar for the combined effect of water nitrate and carotene intake. Nitrate levels in private wells were measured at the time of the interview for 51 cases and 150 controls but were not associated with the risk of NHL after adjusting for pesticide use on the farm. These findings indicate that longterm exposure to elevated nitrate levels in drinking water may contribute to the risk of NHL.

We examined 9 years' incidence of amyotrophic lateral sclerosis, a disease previously associated with a high-selenium environment, in a cohort of 5,182 residents of Reggio Emilia, Italy. This cohort had accidentally been exposed to drinking water with high selenium content. Four cases were diagnosed during the follow-up. Using the remainder of the municipal population as the reference group, the standardized incidence ratio was 4.22 (95% confidence interval = 1.15-10.80). The standardized incidence ratio was higher after limiting the analysis to the subcohort with the longest ascertainable exposure period. The findings appear to confirm a causal association between overexposure to environmental selenium and amyotrophic lateral sclerosis.

We studied the relation between silica and aluminum levels in drinking water and the risk of cognitive impairment using data from a population-based survey of 3,777 French subjects age 65 years and older. We also studied the effect of pH and the concentrations of calcium, magnesium, fluorine, zinc, copper, and iron. We used a mixed effects logistic regression adjusting for age, sex, educational level, and occupation of the subjects. We confirmed the inverse relation previously found between calcium level and cognitive impairment. We found no important association between cognitive impairment and fluorine, magnesium, iron, copper, or zinc. The association between cognitive impairment and aluminum depended on the pH and the concentration of silica: high levels of aluminum appeared to have a deleterious effect when the silica concentration was low, but there was a protective effect when the pH and the silica level were high. The threshold for an aluminum effect, however, was very low (3.5 micrograms per liter) and did not support the hypothesis of a deleterious effect for only high levels of aluminum.

The cardiovascular effects of inorganic arsenic have been documented, but the dose-response relationship between ischemic heart disease (ISHD) and long-term arsenic exposure remains to be elucidated. Mortality rates from ISHD among residents in 60 villages of the area in Taiwan with endemic arseniasis from 1973 through 1986 were analyzed to examine their association with arsenic concentration in drinking water. Based on 1 355 915 person-years and 217 ISHD deaths, the cumulative ISHD mortalities from birth to age 79 years were 3.4%, 3.5%, 4.7%, and 6.6%, respectively, for residents who lived in villages in which the median arsenic concentrations in drinking water were <0.1, 0.1 to 0.34, 0.35 to 0.59, and > or = 0.6 mg/L. A cohort of 263 patients affected with blackfoot disease (BFD), a unique arsenic-related peripheral vascular disease, and 2293 non-BFD residents in the endemic area of arseniasis were recruited and followed up for an average period of 5.0 years. There was a monotonous biological gradient relationship between cumulative arsenic exposure through drinking artesian well water and ISHD mortality. The relative risks were 2.5, 4.0 and 6.5, respectively, for those who had a cumulative arsenic exposure of 0.1 to 9.9, 10.0 to 19.9, and > or = 20.0 mg/L-years compared with those without the arsenic exposure after adjustment for age, sex, cigarette smoking, body mass index, serum cholesterol and triglyceride levels, and disease status for hypertension and diabetes through proportional-hazards regression analysis. BFD patients were found to have a significantly higher ISHD mortality that non-BFD residents, showing a multivariate-adjusted relative risk of 2.5 (95% CI, 1.1 to 5.4).

The presence of a reproductive toxicant in drinking water is one possible explanation of differences in spontaneous abortion rates between women who drink tapwater and those who do not. As part of the investigation conducted by the California Department of Health Services, several routine water quality assays were used to screen water sources available to the populations studied. I reviewed information in the literature about the potential reproductive toxicity of contaminants detected in these assays. None of these contaminants was clearly linked to increased incidence of abortion in the studies reviewed.

Redear sunfish (Lepomis microlophus) were collected from Martin Lake in east Texas. For at least 8 months, 1 year earlier, aqueous selenium-laden effluent from man-made sources was released into this 5,000-acre reservoir (unpublished data). Redear sunfish from a reference lake, 8 km upstream, were collected for comparison to Martin Lake fish. The hepatopancreas (i.e., liver and associated, disseminated exocrine pancrease), mesonephros (i.e., kidney), gonads, heart, spleen, stomach, and gill arches were preserved for histopathological examination using optical and/or transmission electron microscopy. Livers from Martin Lake redear sunfish (which had accumulated approximately 20 ppm selenium in the liver) showed central necrosis, reduced quantities of rough endoplasmic reticulum and glycogen particles, and increased numbers of lysosome-like structures. Kidneys showed proliferative glomerulonephritis, and exocrine pancreas showed marked hypertrophy at the optical level. Ultrastructurally, architectural disorganization, reduced rough endoplasmic reticulum, increased cisternal space, and proliferation of smooth endoplasmic reticulum were evident. The stomach, spleen, gill, heart, and gonads showed no abnormalities.