Risk assessment for ingested inorganic arsenic: A review and status report

Arsenic presents several unique problems in risk assessment. First, there is no good animal model for arsenic as a carcinogen, although in humans arsenic exposure through inhalation is judged to cause lung cancer and ingested inorganic arsenic is judged to cause skin cancer. Second, detoxification of arsenic through methylation is believed to be important, but the mechanisms and the quantitative relationships are not yet understood.EPA provided a risk assessment for ingested inorganic arsenic in its 1984 Health Assessment Document and a revised version in 1988. In both cases EPA calculated a cancer potency or slope factor using epidemiological data from Taiwan. EPA's standard or default risk assessment procedure is to use the linear coefficient from the multistage model in order to calculate cancer risk. This procedure was challenged by the EPA Science Advisory Board (SAB) in a report to the Administrator in September of 1989. The SAB recommended that EPA (1) develop a revised risk assessment based on estimates of the delivered dose of non-detoxified arsenic to target tissues, and (2) consider the potential reduction in cancer risk due to detoxification in establishing an MCL for arsenic.This paper will draw upon the author's experience with the SAB to summarise major issues in arsenic risk assessment and to examine how these issues might be resolved through further research.     

福建省稻米中的砷水平及其健康风险研究

为更好了解区域水平上水稻(OryzasativaL.)砷所引起的健康风险,在福建省9个地区采集了206份水稻样品并对其总砷和无机砷含量进行了分析,然后在此基础上建立风险评价模型并对其健康风险进行了评价。结果表明,福建省水稻精米中总砷平均含量为(0.105±0.091)mg·kg-1,无机砷平均含量为(0.045±0.019)mg·kg-1。全省所有样品中无机砷含量符合中国国家标准规定的限量标准(MCL)0.15mg·kg-1。通过膳食调查的数据和水稻无机砷含量对每天通过稻米消费无机砷摄入量进行了计算,全省平均每天无机砷摄入量为13.50μg,并且9个地区每天无机砷摄入量均超过了美国国家研究委员会所规定的最大限量标准10μg·d-1。根据无机砷摄入量和癌症斜率因子所构建的癌症风险模型结果表明,福建省稻米无机砷所引起的癌症风险为每100000有37.5人,虽然低于中国的平均水平(每100000有61人),但是超过了美国国家环境保护局所规定的可以接受的癌症风险的上限(每100000人有10人)。因此,需要进一步通过流行病学方面的调查来确定福建省稻米无机砷摄入和健康风险之间的关系。     

Health risk assessment for arsenic contaminated soil

This paper describes risk assessment methods for two chronic exposure pathways involving arsenic contaminated soil, namely inhalation of fugitive dust emissions over a lifetime, and inadvertent soil/house dust ingestion. The endpoint in the first case is assumed to be lung cancer and in the second case skin cancer. In order to estimate exposures, inhalation rates and soil/dust ingestion rates are estimated for different age groups; indoor/outdoor time budgets for different age groups are developed; and indoor surface dust and air arsenic concentrations are estimated based on outdoor concentration measurements. Differences observed in indoor/outdoor ratios and arsenic containing dust particle size among different types of communities are noted, as well as possible relationship of particle size to bioavailability. Calculations of risk are presented using cancer potency factors developed by the U.S. Environmental Protection Agency, and uncertainties in these toxicity estimates are described based on: (1) evidence that arsenic may be neither a cancer initiator nor promotor, but may act instead as a late stage carcinogen and (2) evidence that the arsenic dose-response relationship for ingestion may be nonlinear at low doses due to increasing methylation of inorganic arsenic. The first of these considerations influences the relative importance ascribed to arsenic doses in different age groups. The latter consideration indicates that the risk estimates described here are probably very conservative.     

Human carcinogenesis by arsenic

Arsenic is one of the few human carcinogens for which there is not yet a reliable animal cancer model. As such, the classification of arsenic as a carcinogen is based upon data derived from human epidemiologic studies. Although the mechanisms of action of arsenic as a toxic agent have been known for many years, the inability to produce cancer with arsenic in laboratory animals has confounded the operational characterisation of arsenic as initiator, promoter, complete carcinogen, or cocarcinogen for humans. Arsenic is clearly a genotoxic agent that induces chromosomal aberrations, micronuclei and sister chromatid exchange in mammalian cells as well as neoplastically transforms Syrian hamster embryo cells; however, it is not a classical point mutagen. This paper reviews some of the scientifically based issues relating to arsenic and risk assessment.     

Assessment of natural arsenic in groundwater in Cordoba Province,Argentina

Groundwater in the central part of Argentina contains arsenic concentrations that, in most cases, exceed the value suggested by international regulations. In this region, Quaternary loessical sediments with a very high volcanic glass fraction lixiviate arsenic and fluoride after weathering. The objectives of this study are to analyze the spatial distribution of arsenic in different hydrogeological regions, to define the naturally expected concentration in an aquifer by means of hydrogeochemistry studies, and to identify emergent health evidences related to cancer mortality in the study area. The correlation between arsenic and fluoride concentrations in groundwater is analyzed at each county in the Cordoba Province. Two dimensionless geoindicators are proposed to identify risk zones and to rapidly visualize the groundwater quality related to the presence of arsenic and fluoride. A surface-mapping system is used to identify the spatial variability of concentrations and for suggesting geoindicators. The results show that the Chaco-Pampean plain hydrogeologic region is the most affected area, with arsenic and fluoride concentrations in groundwater being generally higher than the values suggested by the World Health Organization (WHO) for drinking water. Mortality related to kidney, lung, liver, and skin cancer in this area could be associated to the ingestion of arsenic-contaminated water. Generated maps provide a base for the assessment of the risk associated to the natural occurrence of arsenic and fluoride in the region.     

Evaluation of the validity of the US EPA's cancer risk assessment of arsenic for low-level exposures: a likelihood ratio approach

Skin cancers associated with ingesting of arsenic have been documented since the 19th century. A study in the southwestern coastal area of Taiwan where people drank well water containing arsenic is generally recognised as providing the best data available for quantifying the risk, and the US Environmental Protection Agency (EPA) used these data to conduct a risk assessment of arsenic ingestion. However, the lowest exposure category in the Taiwan study included arsenic levels up to 290 µg L^–1, which is nearly six times higher than the current EPA maximum contaminant level (MCL), 50 µg L^–1. Therefore, the EPA risk assessment model extrapolated data on high-level exposures to generate risk estimates for low-level exposures. To evaluate the validity of this model, we conducted a quantitative review of epidemiological studies observing arsenic exposures below 290 µg L^–1. A ratio of the likelihood of the EPA model being inappropriate to that of it being appropriate was calculated for each study population as a measurement of the validity of the EPA model. Although existing human data on low-level exposures are limited, the review suggested that the EPA model is unlikely to be able to predict the risk of skin cancer accurately when the arsenic exposure level is between 170 and 270 µg L^–1.     

Likelihood Ratio Analysis of Skin Cancer Prevalence Associated with Arsenic in Drinking Water in the USA

Several published studies have examined skin-cancer prevalence in regions of the USA that have concentrations of arsenic above the USA drinking-water standard. Those studies with adequate exposure and health outcome data did not report any skin cancer cases. Because the USA's arsenic concentrations are relatively low compared to some other countries and the study populations are small, the absence of reported skin-cancer cases could be due to an absence of risk in USA populations or random variability from a predicted risk. We used the current EPA arsenic cancer slope factor (CSF) model, which is derived from Taiwanese populations exposed to high levels of arsenic, to predict the expected number of skin cancers. We then conducted a likelihood ratio analysis, which showed that a null hypothesis (no additional skin cancer risk from arsenic) was approximately 2.2 times more likely than the hypothesis that ingested arsenic causes the predicted rate of skin cancers. Although based on small numbers, our analysis of USA populations indicates that the CSF derived from arsenic exposure in Taiwanese populations may be an overestimate when applied to USA populations.     

地方性砷中毒地区环境砷暴露健康风险研究进展

自然因素引起的环境高砷暴露及其健康效应,尤其是饮水型地方性砷中毒是砷污染健康风险评估的基础。总结地方性砷中毒在环境砷暴露的风险识别、暴露途径和暴露与健康效应关系研究中的作用基础上,指出了地方性砷中毒研究中仅强调了饮水污染,关注的暴露途径比较单一,因此,人体多途径联合砷暴露的健康风险评估过程存在较大的不确定性。我国是唯一存在饮水和燃煤2种自然环境高砷暴露的国家,是研究2种类型砷暴露异同的天然场地,然而目前环境高砷的暴露及其健康效应的研究均为独立研究,对燃煤型地方性砷中毒在呼吸链砷暴露风险评估中的作用重视不够。因此,通过开展两种环境砷暴露及其健康效应的综合比较研究,建立呼吸链暴露评估和暴露-健康效应模型,可以为人体多途径联合砷暴露的健康风险研究提供新的依据。     

Arsenic toxicity in humans: Research problems and prospects

The disposition and toxicity of the metalloid, arsenic, is affected by its oxidation state and on the extent to which it is converted to methylated species. Given that these chemical modifications influence the fate and action of arsenic, new research efforts should be directed both towards elucidating the molecular processes involved in the metabolism of arsenic and in characterising interindividual variation in capacity for processes such as the methylation of arsenic. This information will contribute to a better understanding of the mechanisms of arsenic toxicity and carcinogenicity and to a better assessment of the hazards associated with chronic exposure to this agent.     

Arsenaufnahme von Wildpflanzen auf einem kampfstoffkontaminierten Rüstungsaltlastenstandort

The risk assessment of former ammunition factories, where chemical weapons consisting of diphenylarsenic compounds have been produced or stored is difficult because of the lack of data concerning bioavailability and metabolism of the residues of these sternutators. In order to estimate the contamination of fodder plants by typical pollutants of the former Heeresmunitionsanstalt Löcknitz, the total concentration of arsenic was determined in 186 samples of wild plants. The total arsenic concentration in plants of high feed value did not exceed 1 ppm, whereas 15% of the samples of plants of middle and little value in regard to animal fodder showed arsenic concentrations above 1ppm. The uptake of arsenic by wild plants, however, appears to be comparably low taken the high-grade contamination of the soil into account. A final toxicological evaluation of the risk potential is not yet possible because it requires the characterization of the anorganic and organic arsenic compounds in these plants.     

Uncertainty analysis of a pharmacokinetic modeling for inorganic arsenic

This paper presents an uncertainty and sensitivity analysis of a pharmacokinetic modeling of inorganic arsenic deposition in rodents for a short‐term exposure. Efforts to develop the pharmacokinetic model are directed towards predicting the kinetic behavior of inorganic arsenic in the body, including tissue and blood concentrations, and especially, the urinary excretion of arsenic and its methylated metabolites. However, the use of the model raises an important question when fixed values of model parameters are used: how is the uncertainty in the model prediction based on the collective uncertainties in the model inputs? This study focuses on an “epistemic”; uncertainty in order to handle this problem. In this case, the uncertainty refers to an input that has a single value which cannot be known with precision due to a lack of knowledge about items or its measurement. The combination of the pharmacokinetic model and the uncertainty analysis would help understand the uncertainties in risk assessment associated with inorganic arsenic.     

Probabilistic health risk assessment for ingestion of seafood farmed in arsenic contaminated groundwater in Taiwan

Seafood farmed in arsenic (As)-contaminated areas is a major exposure pathway for the ingestion of inorganic As by individuals in the southwestern part of Taiwan. This study presents a probabilistic risk assessment using limited data for inorganic As intake through the consumption of the seafood by local residents in these areas. The As content and the consumption rate are both treated as probability distributions, taking into account the variability of the amount in the seafood and individual consumption habits. The Monte Carlo simulation technique is utilized to conduct an assessment of exposure due to the daily intake of inorganic As from As-contaminated seafood. Exposure is evaluated according to the provisional tolerable weekly intake (PTWI) established by the FAO/WHO and the target risk based on the US Environmental Protection Agency guidelines. The assessment results show that inorganic As intake from five types of fish (excluding mullet) and shellfish fall below the PTWI threshold values for the 95th percentiles, but exceed the target cancer risk of 10^?6. The predicted 95th percentile for inorganic As intake and lifetime cancer risks obtained in the study are both markedly higher than those obtained in previous studies in which the consumption rate of seafood considered is a deterministic value. This study demonstrates the importance of the individual variability of seafood consumption when evaluating a high exposure sub-group of the population who eat higher amounts of fish and shellfish than the average Taiwanese.     

An effective dietary survey framework for the assessment of total dietary arsenic intake in Bangladesh: Part-A—FFQ design

Groundwater contaminated with arsenic (As), when extensively used for irrigation, causes potentially long term detrimental effects to the landscape. Such contamination can also directly affect human health when irrigated crops are primarily used for human consumption. Therefore, a large number of humans are potentially at risk worldwide due to daily As exposure. Numerous previous studies have been severely limited by small sample sizes which are not reliably extrapolated to large populations or landscapes. Human As exposure and risk assessment are no longer simple assessments limited to a few food samples from a small area. The focus of more recent studies has been to perform risk assessment at the landscape level involving the use of biomarkers to identify and quantify appropriate health problems and large surveys of human dietary patterns, supported by analytical testing of food, to quantify exposure. This approach generates large amounts of data from a wide variety of sources and geographic information system (GIS) techniques have been used widely to integrate the various spatial, demographic, social, field, and laboratory measured datasets. With the current worldwide shift in emphasis from qualitative to quantitative risk assessment, it is likely that future research efforts will be directed towards the integration of GIS, statistics, chemistry, and other dynamic models within a common platform to quantify human health risk at the landscape level. In this paper we review the present and likely future trends of human As exposure and GIS application in risk assessment at the landscape level.     

组织残留法在水生生物基准中的应用概述

水生生物基准已成为生态风险评价和水环境管理的主要参考依据,在水污染治理、控制和管理以及水生生物保护方面发挥着重要作用。环境和生物学参数对基于水体或沉积物等外暴露浓度的毒性阈值和环境基准存在影响,使其具有变异性和不确定性。而基于组织残留的毒性剂量指标可以减少毒性值的变异性以及不确定性,特别是对于生物累积性物质而言,在毒性效应及环境基准研究中存在显著优势。针对组织残留法在水生生物基准研究中的应用,对组织残留法的概念、优势、应用,以及组织残留基准的推导方法等几个方面进行了综述,并提出了组织残留法在应用中存在的关键问题及建议,旨在推动环境基准、生态风险评价理论和方法的研究,以及为水环境管理和污染防治提供技术支持。     

Application of geostatistical methods to arsenic data from soil samples of the Cova dos Mouros mine (Vila Verde-Portugal)

A total of 286 soil samples were collected in the Cova dos Mouros area. All samples were dry sieved into the <200 mesh size fraction and analysed for Fe, Cu, Zn, Pb, Co, Ni, Bi and Mn by atomic absorption spectrometry (AAS) and for As, Se, Sb and Te by atomic absorption spectrometry-hydrid generation (AAS-HG). Only the results of arsenic are discussed in this paper although the survey was extended to all analysed chemical elements. The purpose of this study was to make a risk probability mapping for arsenic that would allow better knowledge about the vulnerability of the soil to arsenic contamination. To achieve this purpose, the initial variable was transformed into an indicator variable using as thresholds the risk-based standards (intervention values) for soils, as proposed by [Swartjes 1999. Risk based assessment of soil and groundwater quality in the Netherlands: Standards and remediation. J. Geochem. Explor.73 1–10]. To account for spatial structure, sample variograms were computed for the main directions of the sampling grid and a spherical model was fitted to each sample variogram (arsenic variable and indicator variables). The parameters of the spherical model fitted to the arsenic variable were used to predict arsenic concentrations at unsampled locations. A risk probability mapping was also done to assess the vulnerability of the soil towards the mining works. The parameters of the spherical model fitted to each indicator variable were used to estimate probabilities of exceeding the corresponding threshold. The use of indicator kriging as an alternative to ordinary kriging for the soil data of Cova dos Mouros produced unbiased probability maps that allowed assessment of the quality of the soil.     

Principles and application of an in vivo swine assay for the determination of arsenic bioavailability in contaminated matrices

The assessment of arsenic (As) bioavailability from contaminated matrices is a crucial parameter for reducing the uncertainty when estimating exposure for human health risk assessment. In vivo assessment of As utilising swine is considered an appropriate model for human health risk assessment applications as swine are remarkably similar to humans in terms of physiology and As metabolism. While limited in vivo As bioavailability data is available in the literature, few details have been provided regarding technical considerations for performing in vivo assays. This paper describes, with examples, surgical, experimental design and analytical issues associated with performing chronic and acute in vivo swine assays to determine As bioavailability in contaminated soil and food.     

Implementation of food frequency questionnaire for the assessment of total dietary arsenic intake in Bangladesh: Part B, preliminary findings

Dietary intake of water and food has been identified as one of the major pathways for arsenic (As) exposure in the rural population of Bangladesh. Therefore, realistic assessment and measurement of dietary intake patterns are important for the development of an accurate estimate of As exposure and human health risk assessment. One important consideration is to identify an appropriate tool for measuring dietary intake. In this study an interviewer-administered Food Frequency Questionnaire (FFQ) was implemented to determine age and gender specific dietary intake. The developed FFQ was unique because it developed a synergy between field dietary assessment and As concentration measurements in various environmental media. The resulting integrated database provided an accurate framework for the process of As exposure and human health risk assessment. The preliminary results reported here from the FFQ demonstrated that this technique could be used in rural areas as a tool to assess As exposure and the associated human health risk.     

Health risk estimates for groundwater and soil contamination in the Slovak Republic: a convenient tool for identification and mapping of risk areas

We undertook a quantitative estimation of health risks to residents living in the Slovak Republic and exposed to contaminated groundwater (ingestion by adult population) and/or soils (ingestion by adult and child population). Potential risk areas were mapped to give a visual presentation at basic administrative units of the country (municipalities, districts, regions) for easy discussion with policy and decision-makers. The health risk estimates were calculated by US EPA methods, applying threshold values for chronic risk and non-threshold values for cancer risk. The potential health risk was evaluated for As, Ba, Cd, Cu, F, Hg, Mn, NO₃ ^?, Pb, Sb, Se and Zn for groundwater and As, B, Ba, Be, Cd, Cu, F, Hg, Mn, Mo, Ni, Pb, Sb, Se and Zn for soils. An increased health risk was identified mainly in historical mining areas highly contaminated by geogenic–anthropogenic sources (ore deposit occurrence, mining, metallurgy). Arsenic and antimony were the most significant elements in relation to health risks from groundwater and soil contamination in the Slovak Republic contributing a significant part of total chronic risk levels. Health risk estimation for soil contamination has highlighted the significance of exposure through soil ingestion in children. Increased cancer risks from groundwater and soil contamination by arsenic were noted in several municipalities and districts throughout the country in areas with significantly high arsenic levels in the environment. This approach to health risk estimations and visualization represents a fast, clear and convenient tool for delineation of risk areas at national and local levels.     

A review of arsenicals in biology

The most toxic form of arsenic is arsine gas. Arsenite is also highly toxic and arsenate is moderately toxic. Arsine gas will lyse red blood cells, arsenite inactivates particular enzymes and arsenate uncouples oxidative phosphorylation. Arsenic does not appear to be a significant mutagen. Epidemiological studies have implicated arsenic as a cause of lung cancer and skin cancer, but arsenic generally does not induce cancer in laboratory animals. Arsenic may bioaccumulate in some plants and marine organisms. Bacteria can be resistant to arsenic by preventing arsenate from entering the cell (chromosomal resistance) or pumping arsenic out of the cell (plasmid resistance). Many different organisms, including mammals, have the ability to methylate inorganic arsenic. Biomethylation seems to be a mechanism of arsenic detoxification.     

北京市某废弃化工厂的人类健康风险评价

由于北京城市化速度的加快,五环路内的工厂将陆续搬迁,搬迁后的土地,使用功能将发生根本性变化,由于修复成本较高,是否对受污染土地进行修复,需要借助健康风险评价,以便确保人们的健康安全.运用美国的健康风险评价框架,对北京市某废弃化工厂场地进行了健康风险分析,计算了将该废弃场地用作居住用地对人类的健康风险指数及确定是否需要进行修复.在场地内,分2次进行了3层土壤采样,共采集到80个样品.选取Cr、Zn、Ni、Pb、Hg、Cu、As、Cd、DDT、六六六(HCH)和邻苯二甲酸二辛酯(DP)11种超标污染物作为目标污染物,对其进行健康风险评价.按照美国EPA的方法,选取了95%置信上限含量进行风险指数的计算.评价结果显示,该场地成人的非致癌风险指数为15.85,儿童的非致癌风险指数为18.17,均超过了非致癌风险指数可接受值1.0,表明该化工厂场地对成人和儿童均有非致癌风险;对成人,邻苯二甲酸二辛酯的致癌风险指数为不可接受值(>1×10-4),对儿童,邻苯二甲酸二辛脂和DDT的致癌风险为不可接受值(>1×10-4),其它污染物的致癌风险均在可接受范围之内.由于案例中的场地将被用作居住用地,建议对该场地进行部分修复.