Charles O. Abernathy

Exposure to Inorganic Arsenic from Fish and Shellfisha

Publisher Summary Humans are exposed to arsenic (As) from many sources, such as food, water, air, and soil. Most foods contain both organic and inorganic forms of As and the inorganic compounds are generally considered to be more toxic. Although fish and shellfish are major contributors to dietary As among seafood consumers, over 90% of the As in seafood is generally organic rather than inorganic. Thus, it is important to know the relative levels of various As species in fish and shellfish when estimating risks from seafood consumption. Data were collected from published and unpublished literature on the concentrations of total, inorganic and organic As present in fish and shellfish. Distributions were skewed with median concentrations, in this instance, a better representation of central tendency than mean concentrations. The data were used to estimate total exposure to inorganic As from consumption of fish/shellfish for several exposure scenarios applicable to seafood-consuming populations, including subsistence groups. Data on fish and shellfish consumption patterns were derived from the 1989–1991 U.S. Department of Agriculture Continuing Survey of Food Intake by Individuals. Organic As in ocean and estuarine fish and shellfish is primarily present as arsenobetaine (AsB) with smaller amounts as arsenocholine (AsC) or other organic compounds. Less is known about the identity of the organic As in freshwater fish. Data on the toxicokinetics of AsB and AsC demonstrate that the As in these compounds is apparently not bioavailable for interaction with other biological molecules.

Consequences of acute and chronic exposure to arsenic in children.

Arsenic is a toxic chemical and may cause adverse health effects in children and adults. It is known to affect the nervous, gastrointestinal, and hematological systems and cause skin and internal cancers in people exposed to levels greater than 300 ppb in their drinking water. For most people, the major exposure to arsenic comes from food (8 to 14 microg inorganic arsenic per day), but when the arsenic level in water is elevated, drinking water becomes the predominant source of exposure. Because it is very difficult to limit arsenic exposure from food, it would be wise to limit arsenic exposure from those more controllable sources. Pediatricians should ascertain the levels of arsenic in drinking water of patients with high arsenic levels, using the supplier or, in the case of private wells, a professional water-testing laboratory assay. The Safe Drinking Water Act does not cover private wells or those water systems with less than 15 hook-ups or those that serve less than 25 people. Pediatricians should instruct parents to use prepared baby formulas or prepare them using water with the arsenic removed and to curtail playing time for younger children in places that have sand containing large amounts of arsenic. Such procedures will limit arsenic exposure to a minimum.

Drug-Induced Cholestasis in the Perfused Rat Liver and Its Reversal by Tauroursodeoxycholate: An Ultrastructural Study

Abstract Chlorpromazine at a concentration of 250 μM and estradiol-17β-D-glucuronide at 17.5 μM on infusion led to a sharp reduction in bile flow by the in vitro perfused rat liver. This was accompanied by fragmentation and a loss of canalicular microvilli, dilatation of canaliculi, and thickening of pericanalicular ectoplasm. Less prominent were the smooth endoplasmic reticulum dilatation, lysosomal lamination, and the appearance of amorphous bile in hepatocyte cytoplasm. The bile flow and electron microscopy appearance were restored to normal by infusion of tauroursodeoxycholate in a concentration of 5 μmol/min for the estradiol-17β-D-glucuronide-induced cholestasis and 1.5 μmol/min for the chlorpromazine-induced cholestasis. Changes in ultrastructure paralleled changes in bile flow. These observations demonstrate the feasibility of electron microscopy studies on the perfused liver, and the rapidity with which cholestatic changes appear.

Estimating Total Arsenic Exposure in the United States

Publisher Summary Arsenic (As) is a component of the earths crust and is ubiquitous in the environment. Consequently, humans are exposed to As from a variety of sources, such as food, water, air, and soil. For the majority of people in the United States, the major exposure route is through the consumption of food. Ingestion of soil, dust, or water contaminated with As also occurs in the areas with naturally elevated As levels or near hazardous waste sites. In addition, there are some people whose cultural practices, such as the use of herbal medicines, may cause additional exposures to As. The dermal absorption of As may occur if activities, such as rice farming, require daily exposure to water contaminated with As. Unfortunately, many exposure scenarios only consider one type of exposure, such as exposure to As in soil. It is critical to obtain a complete exposure estimate, especially at lower doses, to be certain that the exposure data used for the risk assessment does not underestimate the true exposure and presents an unrealistic value.

Risk assessment in the Environmental Protection Agency

Risk assessment is the general process used to determine the potential risk of an adverse health effect occurring from exposure to an agent. It consists of a hazard identification, a dose-response evaluation, an exposure assessment and a risk characterization. At the U.S. Environmental Protection Agency, risk assessments are used to estimate risks from environmental contaminants. Risk management uses the risk characterization along with such variables as economic, social, legal, technical, analytical and political factors to arrive at a regulatory level. The public is informed of regulatory actions prior to and after promulgation of the final rule through the process of risk communication.

Some Comments on the Selection of Human Intraspecies Uncertainty Factors

ABSTRACT The Reference Dose (RfD) is used in the risk assessment of non-carcinogenic chemicals. It is derived by dividing a point of departure by the product of the uncertainty (UFs) and modifying factors (MFs). Separate UFs are used for different variables, e.g., intraspecies variation and, in general, each UF is an order of magnitude (10-fold). On the other hand, the MF is usually based on some known variable such as differences in absorption of a chemical from food and water and its default value is one. The USEPAs Integrated Risk Information System (IRIS) has 14 chemicals that have RfDs based on human studies. We examined those IRIS files to determine the rationale for setting human intraspecies uncertainty factors (UFH). The first consideration was that the chemical had an adequate peer-reviewed human database. Without such, it would not be possible to derive an RfD based on human data. Ten of the 14 chemicals had an UFH of 1 or 3; four of these were essential trace elements (ETEs). The rationales for using less than a 10-fold UFH for the ETEs included; 1) nutritional data, 2) large human exposure groups, 3) minimal effect levels and/or 4) several studies with similar effect levels. For the other compounds, reasons included; 1) large human exposure groups, 2) a critical effect that was not adverse (cosmetic), 3) the most sensitive population was exposed, 4) the compound was on the FDAs “generally regarded as safe” (GRAS) list, 5) database uncertainties and 6) less-than-lifetime exposure adjusted for 70 years exposure. It is important to understand the reasons for selecting a UFH of 1, or 3 as they will apply to future chemicals considered by the USEPA and other agencies.

Effects of Bile Salt Infusion on Chlorpromazine-lnduced Cholestasis in the Isolated Perfused Rat Liver

Abstract The present study has demonstrated that tauroursodeoxycholate (TUDC), but not taurocholate, can reverse chlorpromazine (CPZ)-induced cholestasis in the isolated perfused rat liver. At an infusion rate of 1.5 μmol/min, TUDC led to restoration of bile flow in the perfused rat liver made cholestatic by the addition of 250 μM CPZ. This reversal was accompanied by an increased excretion of CPZ and its metabolites. A higher infusion rate of 5.0 μmol TUDC/min, however, led to only a transient increase in bile flow and to no increase in CPZ excretion. In contrast to the effects of TUDC, infusion of taurocholate led to an exacerbation of CPZ-induced cholestasis. The differences in the efficacy of the two bile salts may be due to their relative detergent (hydrophobic) properties.

Sensitivity Analysis of U.S. EPA's Estimates of Skin Cancer Risk from Inorganic Arsenic in Drinking Water

The current U.S. Environmental Protection Agencys (USEPAs) risk analysis on the Integrated Risk Information System (IRIS) for arsenic in drinking water is based on an epidemiological study of skin cancer in Taiwan. Assumptions used in the USEPA application of the multistage-Weibull model for risk estimation were varied to assess the effect on predicted risk of skin cancer to the U.S. population at arsenic concentrations of 1 to 50 µg/L in drinking water. Among the assumptions tested, the only notable change in risk estimates was a reduction when the arsenic concentration used as representative for Taiwan villages in the low range (<300 µg/L) was increased to the 75th percentile (245 µg/L) in place of the mean used in the USEPA analysis (170 µg/L), but the representative value for Taiwan villages in the high range (≥600 µg/L) was not increased simultaneously to the 75th percentile. Additionally, a simulation study was conducted using records of arsenic measurements in wells from the same period and region of Taiwan as the original study. The exposure-response curve estimated from 60 villages (60 data points) differed only marginally from the outcome when data were summarized into four data points (as in the USEPA skin cancer analysis). Briefly discussed are differences between the study area of Taiwan and the U.S. in nutritional status and consumption of inorganic arsenic in food that might bias predicted U.S. skin cancer risks.

Jaundice of Systemic Infection

A variety of infectious diseases may produce jaundice or other biochemical abnormalities, even though the liver is not the primary site of infection.1–3 Despite the often serious nature of the infection or underlying disease process, the hepatic aspects are generally not life-threatening. However, the assorted liver aspects can mimic extrahepatic obstructive jaundice, making it important to identify the source of the hepatic dysfunction using such imaging techniques as ultrasonography or computed tomography (CT) or performing the appropriate Cholangiographic procedures.4