First Draft prepared by Dr Charles Abernathy Office of Water, Office of Science and Technology Health and Ecological Criteria Division United States Environmental Protection Agency, Washington, DC, USA Revised/edited by Ann Morgan January 2001 Chapter 3 EXPOSURE AND HEALTH EFFECTS CONTENTS 3. EXPOSURE AND HEALTH EFFECTS........................................................ 3 3.1 Exposure Processes and Exposure Assessment..................................... 3 3.1.1 Environmental Levels.............................................................. 3 3.1.1.1 Air and rain water....................................................... 3 3.1.1.2 Soils............................................................... 4 3.1.1.3 Surface water................................................ 4 3.1.1.4 Groundwater................................................. 9 3.1.1.5 Biota............................................................. 13 3.1.2 Exposure in the general population........................................ 14 3.1.2.1 Air................................................................ 14 3.1.2.2 Food and beverages..................................... 14 3.1.2.3 Drinking water............................................. 17 3.1.2.4 Soil.............................................................. 18 3.1.2.5 Miscellaneous exposures............................ 19 3.1.3 Occupational Exposures....................................................... 19 3.1.4 Total intake from all environmental pathways..................... 21 3.2 Kinetics and metabolism.................................................................... 22 3.2.1 Inorganic arsenic .................................................................. 23 3.2.1.1 Absorption.................................................. 23 3.2.1.2 Distribution................................................. 24 3.2.1.3 Metabolic transformation........................... 26 3.2.1.4 Elimination and excretion........................... 27 3.2.1.5 Retention and turnover................................ 28 3.2.1.6 Reaction with body components................. 29 3.2.2 Organic arsenic compounds................................................. 29 3.2.2.1 Absorption.................................................. 29 3.2.2.2 Distribution................................................ 31 3.2.2.3 Metabolic transformation........................... 31 3.2.2.4 Elimination and excretion.......................... 31 3.2.2.5 Retention and turnover.............................. 32 3.2.3 Biomarkers of arsenic exposure........................................... 32 3.2.3.1 Arsenic in hair and nails............................ 32 3.2.3.2 Blood arsenic............................................. 33 3.2.3.3 Arsenic and metabolites in urine............... 34 3.3 Health effects.................................................................................... 35 3.3.1 Acute effects (short-term exposures)................................... 35 3.3.2 Chronic effects (long-term exposures)................................ 36 3.3.2.1 Vascular diseases...................................... 36 3.3.2.2 Cancer ...................................................... 47 3.3.2.3 Genotoxicity and related end-points......... 74 3.3.2.4 Diabetes mellitus ..................................... 79 3.3.2.5 Neurological effects................................. 80 3.3.2.6 Reproductive effects ............................... 80 3.4 Evaluation of human health risks .................................................. 81 3.4.1 Environmental levels and human exposures...................... 81 3.4.2 Critical issues relating exposure to dose........................... 83 3.4.3 Risk evaluation.................................................................. 84 ******* 2 Chapter 3 EXPOSURE & HEALTH EFFECTS 3.1 EXPOSURE ASSESSMENT Given its ubiquitous nature in the environment, human exposure to arsenic is inevitable. Exposure can occur via all three principal routes, that is, through the inhalation of air, through the ingestion of food and water, and via dermal absorption. Worldwide, the degree of non-occupational exposure to arsenic varies greatly, being dependent on local geochemistry and the level and proximity of anthropogenic activity. Elevated environmental exposure to arsenic tends to be confined to relatively small, geologically arsenic-rich areas where levels of arsenic, particularly in drinking water, exceed those found elsewhere by an order of magnitude or more. 3.1.1 ENVIRONMENTAL LEVELS Arsenic is a natural component of the earth’s crust where it is present at an average concentration of 2 mg/kg. Trace concentrations are found in all environmental media, including air, water, soils/sediments and biota. Available data on typical environmental levels are summarized in the following subsections. 3.1.1.1 Air and rainwater Levels of arsenic in ambient air are generally low. In most remote and rural areas, concentrations average between 0.02 and 4 ng/m3. Higher concentrations are evident in many urban areas, with levels ranging typically from 3 to about 200 ng/m3. Concentrations in excess of 1000 ng/m3 have, however, been measured in the vicinity of industrial sources, especially near non-ferrous metal smelters (WHO, 2001). In air, arsenic exists predominantly absorbed on particulate matter, and is usually present as a mixture of arsenite and arsenate, with the organic species being of negligible importance except in areas of arsenic pesticide application or biotic activity. (Beavington & Cawse, 1978; Brimblecombe, 1979; Davidson et al., 1985; Peirson et al., 1974). A recent Europe-wide survey has found evidence of a gradual decline in ambient arsenic concentrations over the past few decades. This reduction in air arsenic is attributed to the progressive introduction of dust abatement equipment at industrial facilities. Typical arsenic levels for the European region are currently quoted as being between 0.2 – 1.5 ng/m3 in rural areas, 0.5 – 3 ng/m3 in urban areas and no more than 50 ng/m3 in industrial areas (DG Environment, 2000). Arsenic has been detected in rainwater. In non-polluted areas, mean concentrations range from 0.013 to 0.5 ug/L (Scudlark & Church, 1988; Andreae, 1980), whereas near a North Sea gas platform, mean arsenic concentrations up to 45 ug/L have been reported (Peirson et al., 1974). 3 3.1.1.2 Soils Background concentrations of arsenic in soil range from 1 to 40 mg/kg, with a mean value of 5 mg/kg (Beyer & Cromartie, 1987; Bowen, 1979). Soils overlying naturally arsenic-rich geological deposits, such as sulphide ores, may have significantly higher concentrations, in some cases up to two orders of magnitude higher (NAS, 1977). Whereas non-contaminated soils typically contain low levels of arsenic, human activity (for example, waste disposal and pesticide applications) can increase substantially the concentrations found in soils. Extremely high arsenic concentrations have been reported in soils contaminated with mine or smelter wastes (up to 27 000 mg/kg), and levels of 20 100 to 35 500 mg/kg have been found in soils around the effluent dumping point of an arsenical pesticide manufacturing plant (US EPA, 1982; Chatterjee & Mukherjee, 1999). In addition, mean total arsenic concentrations of 50 to 550 mg/kg have been recorded in agricultural soils applied with various arsenical pesticides (Sanok et al., 1995; Takamatsu et al., 1982; Walsh & Keeney, 1975; Stilwell & Gorny, 1997). Some peats and sewage sludges have been reported to contain considerable quantities of arsenic. Reported concentrations in peats vary from around 4 mg/kg up to 340 mg/kg (Minkkinen & Yliruokanen, 1978; Shotyk, 1996). Zhu & Tabatabai (1995) monitored total arsenic levels in sewage sludge from waste treatment plants in Iowa (USA) and found concentrations which ranged from 2.4 to 39.6 mg/kg, with a mean of 9.8 mg/kg. Relatively little of the total arsenic measured in soils has been found to be present in bioavailable forms. In one study, which looked at garden soils near or at sites of past mining activity, the water-soluble extractable arsenic fraction was found to be less than 1% of the total (Xu & Thornton, 1985). In similar studies, the proportion of water-extractable arsenic in agricultural top soils ranged from 0.05% to 0.3%, and in mine wastes from 0.02% to 1.2% (Kavanagh et al., 1997). Ng et al. (1998) reported total arsenic concentrations of 32 to 1 597 mg/kg in soils that had been contaminated 30 years previously with arsenical pesticides. Based on a rat model, it was estimated that the absolute bioavailability of these contaminated soils relative to arsenite and arsenate ranged from 1.0 to 9.9% and 0.3 to 3.0%, respectively. 3.1.1.3 Surface water Arsenic is widely distributed in surface water. Concentrations of arsenic in surface waters are usually low, although higher concentrations can occur near natural mineral deposits or near anthropogenic sources. Measured levels of arsenic in surface freshwaters (rivers and lakes) are summarized in Table 3.1. Surveys indicate that most values are below 10 ug/L, although some samples may exceed 1 mg/L 4 (Page, 1981; Smith et al., 1987; Welch et al., 1988). A total arsenic concentration of 2 mg/L has been recorded near one pesticide plant (Faust et al., 1983; Faust et al., 1987). Crearley (1973) reported mean arsenic levels of 3200 and 7900 ug/L in two lakes near a manufacturing plant that had been producing arsenic-based cotton defoliants for 30 years. High levels of arsenic have been