Health Assessment of the Sodium and Potassium Salts of Inorganic Phosphates.
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When assessing the human health effects of phosphorus (P), specifically the sodium and potassium salts of inorganic phosphates, there are two notable departures from the traditional risk assessment approach to consider: 1) background concentrations found in humans are not zero, and 2) background concentrations found in contaminated sites are not zero. Phosphorus, as commonly found in various phosphates, exhibits a “U-shaped” dose-response curve, where dose levels above deficiency, and dose levels below toxicity, overlap across some population subgroups. Thus, care must be taken in the interpretation of extradietary exposures above a standard American diet that may result from exposures at sites contaminated with phosphate at levels above background. Phosphorus is most commonly found in nature in its pentavalent form in combination with oxygen, known as phosphate or orthophosphate anion (PO43−). Phosphorus is an essential constituent of all living organisms, and its chemical forms and concentrations are quite uniform across most plant and animal species. Data from acute human clinical exposures from bowel preparations show clear renal and gastrointestinal toxicity, but these studies are acute, and may not extrapolate to subchronic or chronic durations germane to human health assessments at contaminated sites. Human dietary studies also show renal, cardiovascular, and skeletal endpoints near the same exposure levels when measured as mg P/kg-d. However, the dosimetry in these studies was determined by dietary surveys, completed years after the exposures, and failed to determine the exact forms of Phosphate in the diet, thus the confidence in the exact dosimetry is low. There are, however, robust animal data from acute, subchronic, chronic and developmental studies in several species, with similar endpoints as in humans. In particular, a subchronic dietary study by Ritskes-Hoitinga et al (2004), which showed nephrocalcinosis in rats and rabbits, under conditions where calcium/phosphate ratios were specified (calcium blocks P absorption) appears to be relevant. Several additional animal studies described similar endpoints at slightly higher doses that further support the relevance of this potential point of departure. Doses that revealed renal effects in humans were similar to doses producing renal effects in animals. Disclaimer: The views represented in this abstract are those of the author and do not necessarily reflect those of the United States Environmental Protection Agency.