Risk and revisionism in arsenic cancer risk assessment.

Abstract

Oral exposures of nonoccupational populations to environmental inorganic arsenic are associated with skin and internal cancers as well as various noncarcinogenic effects. Cancer risk assessments have been based largely on epidemiological studies of a large population exposed to inorganic arsenic in well water in Taiwan. Criticisms and skepticism of the use of the Taiwanese data for estimating arsenic cancer risks outside of Taiwan, including potential use by the U.S. Environmental Protection Agency for regulatory purposes, have been expressed on various grounds. The nature and extent of such criticisms have sharpened with recent findings in the exposed Taiwanese of increased incidence of internal cancers (bladder, kidney, liver, and lung), in addition to already-observed skin cancer, coupled with a good likelihood that these findings will produce more stringent arsenic regulation in the United States and elsewhere. These criticisms collectively posit a revisionist view that: 1) cancer incidence among the Taiwanese was amplified by a number of host and environmental factors not applicable elsewhere, 2) the cancer dose-response curve may not be linear at the lower exposures elsewhere, and 3) there is a toxicokinetic and metabolic threshold to cancer risk that was exceeded by the Taiwanese. However, a number of the arguments against wide use of the Taiwanese data are flawed and subject to challenge. We explore some of these arguments and their critical evaluation, particularly as they concern certain exposure, metabolic, and nutritional determinants of the cancer risk of inorganic arsenic in the Taiwanese.

Arsenic Methylation Patterns before and after Changing from High to Lower Concentrations of Arsenic in Drinking Water

“…Urinary arsenic is generally regarded as the most reliable indicator of recent exposure to In-As and is used as the main biomarker of exposure (11,12). In the case of ingestion, experimental studies show that around 60-75% of the dose is excreted in the urine within a few days (8,9,13).…”

Transition from Endothermic to Exothermic Dissolution of Hydroxyapatite Ca5(PO4)3OH–Johnbaumite Ca5(AsO4)3OH Solid Solution Series at Temperatures Ranging from 5 to 65 °C

“…Figure 4 shows the position of the Raman bands for all synthetic phases. The most intensive band in the HAP spectrum (962 cm −1 ) corresponds to the nondegenerate symmetric P-O stretching vibration ν 1 ; whereas in the JBM spectrum, the highest band (845 cm −1 ) corresponds to both ν 1 and ν 3 modes of As-O bond [8,16]. The peak around 580 cm −1 probably results from ν 4 vibrations of the O-P-O bonds [16].…”

“…All solutions were prepared with double-distilled water. Pure JBM and a sample containing 2.0 As were synthesized at 65 • C and at pH between 10.0 and 11.5, maintained with a 23% solution of NH 4 OH [8]. The elevated temperature resulted in better crystallinity of the product.…”

“…An As ion can replace P in the structure of apatite in bones due to the long-term intake of small doses of arsenic. This can lead to the development of cancer in the human body [8]. Thus, there is a need to better understand the reactions that govern the mobility of As in the environment.…”

Metalloid Transport Systems

“…In addition, Trisenox, the active ingredient of which is As(OH) 3 in solution [52], is used clinically as a chemotherapeutic agent for the treatment of acute promyelocytic leukaemia [53,54]. Since AQP9 is expressed in human leukocytes [47], it may be responsible for the chemotherapeutic effects of arsenite by facilitating diffusion of the drug into the leukaemia cells.…”