Assessing Children's Exposures and Risks to Drinking Water Contaminants: A Manganese Case Study

Background: Compared to adults, children maybe more highly exposed to toxic substances in drinking water because they consume more water per unit of body weight. The U.S. Environmental Protection Agency (USEPA) has developed new guidance for selecting age groups and age-specific exposure factors for assessing children's exposures and risks to environmental contaminants. Research Aim: To demonstrate the application and importance of applying age-specific drinking water intake rates, health reference values, and exposure scenarios when assessing drinking water exposures because these approaches illustrate the potential for greater potential for adverse health effects among children. Methods: manganese, an essential nutrient and neurotoxicant, was selected as a case study and chemical of potential concern for children's health. A screening-level risk assessment was performed using age-specific drinking water intake rates and manganese concentrations from U.S. public drinking water systems. Results: When age-specific drinking water intake rates are used to calculate dose, formula-fed infants receive the highest dose of manganese from drinking water compared to all other age groups. Estimated hazard quotients suggest adverse health effects are possible. Use of USEPA's standardized childhood age groups and childhood exposure factors significantly improves the understanding of childhood exposure and risks.     

A Probabilistic Assessment of Household Exposures to MTBE from Drinking Water

The oxygenate methyl tertiary butyl ether (MTBE) has been added to reformulated gasoline in the U.S. to meet national ambient air quality standards. Although MTBE has provided significant health benefits in terms of reduced criteria and toxic air pollutants, detections of MTBE in some groundwater and drinking water sources have raised concerns about potential environmental contamination and human exposures. In this paper, we examine the frequency and concentration of MTBE detections in drinking water sources in California from 1995 to 1999, and provide a preliminary analysis of the distribution of household exposures to MTBE from water-related activities. Using published data on the toxicity and possible cancer hazard posed by MTBE, we estimate the likely cancer and non-cancer risks for the general population in California from past and potential future MTBE exposures. More highly exposed subgroups were also addressed. Our findings indicate that less than 2% of all sampled drinking water sources in California had detectable levels of MTBE in 1999, with average MTBE drinking water concentrations ranging from 0.09 to 4.9?ppb for this year. Both the detection rate for MTBE and average MTBE concentrations have remained relatively stable since 1995, despite increased sampling of drinking water sources in California. The probabilistic exposure analysis suggests that drinking water exposures to MTBE are unlikely to pose a significant health risk for the general population or more highly exposed individuals in California.     

Cancer clusters: findings vs feelings

The issue of cancer clusters, which has been in the spotlight recently, is plagued by a wide disparity between public perceptions and scientific findings. Movies like Erin Brockovich have led the public to think that industrial pollution in the environment is causing local "cancer clusters" where cancer cases are more prevalent due to cancer-causing chemicals. There are many scientifically documented instances in which chemical exposure has caused cancer in humans, but the evidence for purely environmental exposures causing cancer is sparse. The clusters that scientists have been able to attribute successfully to a particular cause have been occupational (such as workers in a factory developing a particular type of cancer from daily exposure to a specific chemical), linked to a particular medicine, or linked to behaviors such as smoking or sunbathing. There is some indication that chemicals dissolved in drinking water may elevate the risk of gastrointestinal and bladder/urinary tract cancers and that living next to a smelter or other "point source" of air pollution may elevate risk of lung cancer. The many efforts that have been made to demonstrate links between other types of cancer and environmental contamination have not conclusively identified such links. Several challenges bedevil any cancer cluster investigation and can result in ambiguous or misleading conclusions. This report discusses the potential cancer clusters in Toms River, New Jersey and Long Island, New York, because they contain many elements typical of cancer cluster investigations and have received considerable media attention.     

HPRT mutations in humans: biomarkers for mechanistic studies.

The X-chromosomal gene for hypoxanthine-guanine phosphoribosyltransferase (HPRT), first recognized through its human germinal mutations, quickly became a useful target for studies of somatic mutations in vitro and in vivo in humans and animals. In this role, HPRT serves as a simple reporter gene. The in vivo mutational studies have concentrated on peripheral blood lymphocytes, for obvious reasons. In vivo mutations in T cells are now used to monitor humans exposed to environmental mutagens with analyses of molecular mutational spectra serving as adjuncts for determining causation. Studies of the distributions of HPRT mutants among T cell receptor (TCR) gene-defined T cell clones in vivo have revealed an unexpected clonality, suggesting that HPRT mutations may be probes for fundamental cellular and biological processes. Use of HPRT in this way has allowed the analyses of V(D)J recombinase mediated mutations as markers of a mutational process with carcinogenic potential, the use of somatic mutations as surrogate markers for the in vivo T cell proliferation that underlies immunological processes, and the discovery and study of mutator phenotypes in non-malignant T cells. In this last application, the role of HPRT is related to its function, as well as to its utility as a reporter of mutation. Most recently, HPRT is finding use in studies of in vivo selection for in vivo mutations arising in either somatic or germinal cells.     

Air pollution combustion emissions: characterization of causative agents and mechanisms associated with cancer, reproductive, and cardiovascular effects

Combustion emissions account for over half of the fine particle (PM(2.5)) air pollution and most of the primary particulate organic matter. Human exposure to combustion emissions including the associated airborne fine particles and mutagenic and carcinogenic constituents (e.g., polycyclic aromatic compounds (PAC), nitro-PAC) have been studied in populations in Europe, America, Asia, and increasingly in third-world counties. Bioassay-directed fractionation studies of particulate organic air pollution have identified mutagenic and carcinogenic polycyclic aromatic hydrocarbons (PAH), nitrated PAH, nitro-lactones, and lower molecular weight compounds from cooking. A number of these components are significant sources of human exposure to mutagenic and carcinogenic chemicals that may also cause oxidative and DNA damage that can lead to reproductive and cardiovascular effects. Chemical and physical tracers have been used to apportion outdoor and indoor and personal exposures to airborne particles between various combustion emissions and other sources. These sources include vehicles (e.g., diesel and gasoline vehicles), heating and power sources (e.g., including coal, oil, and biomass), indoor sources (e.g., cooking, heating, and tobacco smoke), as well as secondary organic aerosols and pollutants derived from long-range transport. Biomarkers of exposure, dose and susceptibility have been measured in populations exposed to air pollution combustion emissions. Biomarkers have included metabolic genotype, DNA adducts, PAH metabolites, and urinary mutagenic activity. A number of studies have shown a significant correlation of exposure to PM(2.5) with these biomarkers. In addition, stratification by genotype increased this correlation. New multivariate receptor models, recently used to determine the sources of ambient particles, are now being explored in the analysis of human exposure and biomarker data. Human studies of both short- and long-term exposures to combustion emissions and ambient fine particulate air pollution have been associated with measures of genetic damage. Long-term epidemiologic studies have reported an increased risk of all causes of mortality, cardiopulmonary mortality, and lung cancer mortality associated with increasing exposures to air pollution. Adverse reproductive effects (e.g., risk for low birth weight) have also recently been reported in Eastern Europe and North America. Although there is substantial evidence that PAH or substituted PAH may be causative agents in cancer and reproductive effects, an increasing number of studies investigating cardiopulmonary and cardiovascular effects are investigating these and other potential causative agents from air pollution combustion sources.     

IPCS guidelines for the monitoring of genotoxic effects of carcinogens in humans. International Programme on Chemical Safety

The purpose of these guidelines is to provide concise guidance on the planning, performing and interpretation of studies to monitor groups or individuals exposed to genotoxic agents. Most human carcinogens are genotoxic but not all genotoxic agents have been shown to be carcinogenic in humans. Although the main interest in these studies is due to the association of genotoxicity with carcinogenicity, there is also an inherent interest in monitoring human genotoxicity independently of cancer as an endpoint.The most often studied genotoxicity endpoints have been selected for inclusion in this document and they are structural and numerical chromosomal aberrations assessed using cytogenetic methods (classical chromosomal aberration analysis (CA), fluorescence in situ hybridisation (FISH), micronuclei (MN)); DNA damage (adducts, strand breaks, crosslinking, alkali-labile sites) assessed using bio-chemical/electrophoretic assays or sister chromatid exchanges (SCE); protein adducts; and hypoxanthine-guanine phosphoribosyltransferase (HPRT) mutations. The document does not consider germ cells or gene mutation assays other than HPRT or markers of oxidative stress, which have been applied on a more limited scale.     

Is Cancer in Israeli Professional Divers Exposed to Polluted Waters an Occupational Disease?

Because there is some contamination of practically every body of water, risk analysis is important to determine diving exposure standards to pollutants, including requirements for protective equipment. In the following study we attempt to determine the increased risk of cancer in Israeli Naval divers exposed to pollutants in the Kishon River system. We calculated two risks, one using maximally recorded levels of pollutants outside the diving areas (worst-case scenario), and the other using maximally recorded levels in the actual diving areas. For both calculations we used conservative assumptions for exposure (2500 exposure hours with 50% of body covered with sediment), and a synergistic risk model. We considered all chemicals that were carcinogenic by inhalation also to be carcinogenic by oral and dermal absorption. The relative risk was 1.13 for the worst-case scenario, and 1.004 for exposures in actual diving areas. We conclude that it is unlikely that exposure to the polluted Kishon River waters can cause a detectable increase in cancer risk in Israeli Navy divers. This study has implications for professional divers exposed to polluted waters.     

Arsenic and Heavy Metal Concentrations in Drinking Water in Pakistan and Risk Assessment: A Case Study

The present study was performed to assess drinking water quality and potential health risk in the Nowshera District, Khyber Pakhtunkhwa, Pakistan. For this purpose drinking water samples were collected from local available sources and analyzed for physico-chemical characteristics, arsenic (As) and heavy metals. Results revealed high levels of toxic heavy metals such as chromium (Cr), nickel (Ni), lead (Pb), cadmium (Cd), and As contaminations in the drinking water. Results were evaluated for chronic risk including average daily intake (ADI) and hazard quotient (HQ). Among heavy metals the HQ values were highest for Cd (5.80) and As (2.00). Therefore, populations in the study area may be at a low level of chronic toxicity and carcinogenic risk. Statistical analyses showed that contribution of different drinking water sources to the mean contaminant levels in the study area was insignificant (p =.53). Correlation analysis further revealed that anthropogenic activities were the main sources of contamination, rather than geogenic. This study strongly recommends the treatment of urban and industrial wastewater in the vicinity of the study area and provision of safe drinking water.     

Atrazine and its metabolites in surface and well waters in rural area and its human and ecotoxicological risk assessment of Henan province,China

A study to monitor atrazine (ATR) and its metabolites in surface and well waters in rural area of Henan province was undertaken. A total of 66 surface water and 38 well water samples were collected during the period from July to August in 2016. The residues of ATR and its metabolites, such as desethylatrazine (DEA), deisopropylatrazine (DIA), and hydroxyatrazine (HA) were analyzed by UPLC-MS/MS. The detection rate of ATR and its metabolites under different pH values was investigated. Based on the survey results, a human health non-carcinogenic and carcinogenic risk assessment was conducted for adults and children. Ecotoxicological risk assessment was also conducted using default endpoint values and the risk quotient method. The results showed that ATR and DEA were the most frequently detected substances, the detection rate of which were 75.0 and 60.6%, respectively, and the level of ATR and its metabolites in this research was in the mid-range when compared with other countries. The detection rate of ATR and DEA in alkali water was much higher than that in acid water. ATR posed low potential non-carcinogenic risk to human through the exposure route of drinking water, and showed acceptable carcinogenic risk estimates for adults and children both in median and highest concentration. Ecotoxicological risk of ATR and DEA assessment revealed acceptable risk.     

Human Health Risk of Metals in Drinking-Water Source Areas from a Forest Zone after Long-Term Excessive Deforestation

The concentrations of 10 metals (As, Cd, Cr, Cu, Fe, Hg, Mn, Pb, Se, Zn) were determined in drinking water in Khingan, China, a forest zone after long-term excessive deforestation. These metals’ concentrations in water exceeded background values of metals in some other regions of the world, indicating that there were other metal sources contributing to such high levels of metals in Khingan. Arsenic was the only metal whose concentration exceeded the maximum levels allowed in drinking water. Principal component analysis showed that As, Cd, Cu, and Se originated from anthropogenic sources and exhibited significantly high concentrations in north Khingan, while Fe and Mn derived from natural formation and showed significantly high concentrations in central Khingan. Health risks from metals were evaluated by a model recommended by the U.S. Environmental Protection Agency. Ingestion was the predominant pathway of exposure to metals in water for local residents. Arsenic was also the only metal causing both noncarcinogenic hazard and carcinogenic risk in Khingan. The high risks occurred mainly in north Khingan and are associated with coal combustion. This study indicates that long-term excessive deforestation may increase As concentration considerably in drinking water and then pose health risks to local residents.     

Genotoxicity of 3'-azido-3'-deoxythymidine in the human lymphoblastoid cell line, TK6: relationships between DNA incorporation, mutant frequency, and spectrum of deletion mutations in HPRT.

Perinatal treatment with 3'-azido-3'-deoxythymidine (AZT) has been found to reduce the rate of maternal-infant transmission of HIV; however, AZT is genotoxic in mammalian cells in vitro and induces tumors in the offspring of mice treated in utero. The purpose of the present study was to investigate the relationships between incorporation of AZT into DNA, and the frequency and spectrum of mutations at the HPRT locus of the human lymphoblastoid cell line, TK6, following in vitro exposures to AZT. Cells were cultured in medium containing 0 or 300 microM AZT for 1, 3, or 6 day(s) (n = 5/group). The effects of exposure duration on incorporation of AZT into DNA and HPRT mutant frequency were determined using an AZT radioimmunoassay and a cell cloning assay, respectively. AZT accumulated in DNA in a supralinear manner, approaching a plateau at 6 days of treatment (101.9 +/- 14.7 molecules AZT/10(6) nucleotides). After 3 days of AZT exposure, HPRT mutant frequency was significantly increased (1.8-fold, p = 0.016) compared to background (mutant frequency = 3.78 x 10(-6)). Multiplex PCR amplification of genomic DNA was used to determine the frequency of exon deletions in HPRT mutant clones from untreated cells versus AZT-treated cells. Molecular analyses of AZT-induced mutations revealed a significant difference in the frequency of total gene deletions (44/120 vs. 18/114 in controls, p = 0.004 by the Mann-Whitney U-statistic). In fact, the Chi-square test of homogeneity demonstrate that the differences between the control and AZT-treatment groups is attributed mainly to this increase in total gene deletion mutations (p = 0.00001). These data indicate that the primary mechanism of AZT mutagenicity in human TK6 cells is through the production of large deletions which occur as a result of AZT incorporation into DNA and subsequent chain termination. The data imply that perinatal chemoprophylaxis with AZT may put children of HIV-infected women at potential risk for genetic damage.     

The carcinogenicity of acrylamide

Acrylamide is carcinogenic to experimental mice and rats, causing tumors at multiple organ sites in both species when given in drinking water or by other means. In mice, acrylamide increases the incidence of alveologenic lung tumors and initiates skin tumors after dermal exposures. In two bioassays in rats, acrylamide administered in drinking water consistently induced peritesticular mesotheliomas, thyroid follicular cell tumors, and mammary gland tumors, as well as primary brain tumors when all such tumors were included in data analysis. In one of the rat bioassays, increased numbers of adrenal pheochromocytomas, adenomas of pituitary and clitoral glands, papillomas of the oral cavity, and adenocarcinomas of the uterus also occurred. In both humans and experimental animals, a significant fraction of ingested acrylamide is converted metabolically to the chemically reactive and genotoxic epoxide, glycidamide, which is likely to play an important role in the carcinogenicity of acrylamide. No studies on the carcinogenicity of glycidamide have been published, but bioassays of this compound are in progress. Epidemiologic studies of possible health effects from exposures to acrylamide have not produced consistent evidence of increased cancer risk, in either occupationally exposed workers or the general populations of several countries in which acrylamide is present in certain foods and beverages. A doubling of risk for pancreatic cancer was observed in the most highly exposed workers within the largest industrial cohort, but no consistent exposure–response relationships were identified. Retrospective re-analyses of previously conducted case-control studies of cancer incidence in several European populations have identified no causal relationship between consumption of foods or beverages that contain acrylamide and the incidence of cancers at various sites including kidney, large bowel, urinary bladder, oral cavity, pharynx, larynx, esophagus, breast, and ovary. These retrospective studies of cancer incidence in relation to acrylamide in food have limited power to detect increased cancer risks, and have been criticized on various grounds, but they do indicate that no major cancer risks are attributable to intake of acrylamide in Western diets.     

Methyl Ethyl Ketone Safety Characterization for Infants and Children: Assessment in the USEPA Voluntary Children's Chemical Evaluation Program

A safety characterization specific to children was performed for methyl ethyl ketone (MEK) according to the guidelines of the Voluntary Children's Chemical Evaluation Program (VCCEP). The characterization indicates that MEK exposures are not expected to pose an acute or chronic risk to children. Hazard information, summarized as per the VCCEP Tier structure, indicated no need for additional studies. All exposure pathways potentially relevant to children were considered, including child contact with environmental media, food, drinking water, parental transfer to child (human milk or dermal contact), direct consumer product use, and presence during product use. The assessment found that exposures from anthropogenic sources that children may encounter on a daily basis are very low, and in particular well below the chronic inhalation and oral health benchmarks (RfC and RfD) derived by the U.S. Environmental Protection Agency (USEPA). Indoor uses of consumer products can result in higher acute exposures, but these are short-lived and also fall below chronic benchmarks adjusted to an acute timeframe. In addition, MEK is rapidly metabolized and excreted, thus acute exposures do not lead to an increase in body burden over time. The USEPA concluded the VCCEP submission sufficiently characterized potential risks to children, and that no additional toxicity tests were needed for MEK.     

Epidemiology of childhood leukemia in the presence and absence of Down syndrome

Down syndrome (DS) is a common congenital anomaly, and children with DS have a substantially higher risk of leukemia. Although understanding of genetic and epigenetic changes of childhood leukemia has improved, the causes of childhood leukemia and the potential role of environmental exposures in leukemogenesis remain largely unknown. Although many epidemiologic studies have examined a variety of environmental exposures, ionizing radiation remains the only generally accepted environmental risk factor for childhood leukemia. Among suspected risk factors, infections, exposure to pesticides, and extremely low frequency magnetic fields are notable. While there are well-defined differences between leukemia in children with and without DS, studies of risk factors for leukemia among DS children are generally consistent with trends seen among non-DS (NDS) children.We provide background on DS epidemiology and review the similarities and differences in biological and epidemiologic features of leukemia in children with and without DS. We propose that both acute lymphoblastic and acute myeloblastic leukemia among DS children can serve as an informative model for development of childhood leukemia. Further, the high rates of leukemia among DS children make it possible to study this disease using a cohort approach, a powerful method that is unfeasible in the general population due to the rarity of childhood leukemia.     

ELF magnetic fields: animal studies, mechanisms of action

Animal studies can contribute to addressing the issue of possible greater health risk for children exposed to 50–60 Hz extremely low frequency (ELF) magnetic fields (MFs), mostly in terms of teratological effects and cancer.Teratology has been extensively studied in animals exposed to ELF MFs but experiments have not established adverse developmental effects.Childhood leukaemia has been the only cancer consistently reported in epidemiological studies as associated with exposure to ELF MFs. This association has been the basis for the classification as “possibly carcinogenic to humans” by the International Agency for Research on Cancer in 2002. Animal experiments have provided only limited support for these epidemiological findings. However, none but one study used an animal model for acute lymphoblastic leukaemia (ALL), the main form of childhood leukaemia, and exposures to ELF MFs were not carried out over the whole pregnancy period, when the first hit of ALL is assumed to occur.Moreover, there are no generally accepted biophysical mechanisms that could explain carcinogenic effects of low-level MFs. The radical pair mechanism and related cryptochromes (CRY) molecules have recently been identified in birds and other non-mammalian species, as a sensor of the geomagnetic field, involved in navigation. The hypothesis has to be tested in mammalian models. CRY, which is part of the molecular circadian clock machinery, is a ubiquitous protein likely to be involved in cancer cell growth and DNA repair.In summary, we now have some clues to test for a better characterization of the interaction between ALL and ELF MFs exposure.     

Tea drinking and cancer risk: epidemiologic evidence

Tea and tea compounds have been shown to inhibit carcinogenic processes in experimental animals, raising the possibility that tea drinking may lower cancer risk in humans. However, epidemiologic studies have produced inconsistent evidence on the relation between tea drinking and cancer risk. Ecological data show considerable international variation in tea consumption but relatively small differences in cancer rates. Results from case-control and cohort studies also are inconclusive. Nevertheless, high consumption of tea has been linked to a reduced risk of digestive tract cancers in a number of epidemiologic studies. A lack of detailed information on duration and amount of tea drinking, a narrow range of tea intake in some study populations, inadequate control for confounding, and potential biases in recall and reporting of tea drinking patterns in case-control studies may have contributed to the diverse findings. Further research is needed before definitive conclusions on tea's impact upon cancer risk in humans can be reached.     

Genotoxic activity of organic contamination of the Songhua River in the north-eastern region of the People's Republic of China

The Songhua River is one of the biggest rivers in China and is the major freshwater source for industry and agriculture, as well as the source of the drinking water for millions of residents living along it. Heavy contamination of the Songhua River is due to domestic sewage and industrial wastewater. Thus, we set out to determine the carcinogenic potential of water samples taken from drinking water source of Harbin city in the Songhua River. Short-term genotoxic bioassays using Ames, SCE, and cell transformation assays were employed to examine the genotoxic activity of the ether extracts of water samples taken from the Songhua River. The results of the Ames test indicated that there were frame shift mutagens in the water samples, which were both direct and indirect. A dose–response relationship for the SCE assay was obtained, and the SCE cumulative frequency moved obviously to the right with increasing doses of water samples. Typical transformed foci were formed in NIH3T3 cells induced by ether extracts of water samples and the transformation frequency showed a dose–response relationship. The transformed cells showed the characteristics of malignant cells. All of the results indicated that the ether extracts of water samples taken from the Songhua River showed genotoxic activity.     

Concentration of arsenic in groundwater,vegetables, human hair and nails in mining site in the Northern Thai Nguyen province,Vietnam: human exposure and risks assessment

This study was aimed to examine the risk of chronic arsenic (As) exposure for the residents living in Nui Phao, Thai Nguyen in the northern Vietnam. Groundwater, vegetables, human hair, and nail samples were collected from volunteers living in Nui Phao. The results revealed that 75% of the groundwater samples had As exceeding the World Health Organization (WHO) drinking water guideline of 10 µg L^?1. The result of As concentration for most of the vegetable samples was greater than the WHO/FAO safe (0.1?mg kg^?1). The result of hair and nail samples in this study showed that 3.5 and 20% of the samples had As concentration exceeding the level of As toxicity in hair and nails, respectively. The result of health risks indicated that the potential health risk of As contamination is greater for groundwater than vegetables. The total hazard quotient (HQ) value through vegetables ingestion and drinking water exceeded 1.0 suggesting potential health risk for local residents. The calculation of potential carcinogenic risk through both consumption of vegetables and drinking water was low cancer risk in adults. Other food sources and the exposure pathways are needed to exactly assess health risks in this area.     

Heavy metal contamination and health risk assessment in drinking water of Sistan and Baluchistan,Southeastern Iran

Access to safe and clean drinking water is an essential element of healthy life also known as the primary human needs. The present study was conducted to investigate heavy metal (HM) concentrations of drinking water. Excess health risk of HM (Cr, Pb, and Cd) intake is related to the drinking water consumption in local population. HMs concentrations were analyzed by using graphite furnace atomic absorption spectrometer and were compared with permissible limits regulated by country and World Health Organization (WHO). The hazard quotient (HQ) and Excess Lifetime Cancer Risk (ELCR) were determined to show the carcinogenic and non-carcinogenic effects of HMs, respectively. HQs were found in the order of Pb > Cd > Cr and subsequently HI index was also estimated for all HM in two age groups (children and adults). The comparisons indicate no possibility of non-carcinogenic effects to the local population. The values for ELCR were found in the order of Cr > Cd > Pb. The ELCR index was found above acceptable risk levels for chromium and cadmium in both children and adults groups. Furthermore, intermetal correlation results revealed that heavy metals have common sources resulting from geogenic and anthropogenic activities and these are major sources of water contamination in Sistan and Baluchestan province.     

广州市饮用水源中硝酸盐亚硝酸盐含量与癌症死亡率联系

本文探讨了饮用水源中硝酸盐和亚硝酸盐污染对癌症死亡率的影响。收集了1991～1998年广州市饮用水源中硝酸盐、亚硝酸盐和癌症死亡率的历史数据,并分析了它们之间的相关性。结果显示,饮用水源中硝酸盐氮和亚硝酸盐氮的总浓度与癌症死亡率呈正相关关系(R²=O.76,P<0.05)。对广州市各区的数据分析表明,饮用水源中亚硝酸盐氮和癌症死亡率有较高的相关性(R²=0.56,P<0.05),且硝酸盐氮和癌症死亡率的相关性也很高(R²=0.66,P<0.01)。这说明了1991～1998年期间,广州市区居民癌症死亡率的逐年递增很可能与饮用水源中硝酸盐和业硝酸盐含量的增加有关。此次研究结果说明饮用水源中的硝酸盐及亚硝酸盐可能是重要的致癌因子。