Comparison of Risk Assessments of Boron: Alternate Approaches to Chemical-Specific Adjustment Factors
Titel:
Comparison of Risk Assessments of Boron: Alternate Approaches to Chemical-Specific Adjustment Factors
Auteur:
Murray, F. Jay Schlekat, Christian E.
Verschenen in:
Human and ecological risk assessment
Paginering:
Jaargang 10 (2004) nr. 1 pagina's 57-68
Jaar:
2004-02
Inhoud:
Health risk assessments of boron (B) have been performed in recent years by seven well-respected regulatory and scientific organizations, including the Institute for Evaluating Health Risks, European Centre for Ecotoxicology and Toxicology of Chemicals, International Programme on Chemical Safety, World Health Organization, National Academy of Sciences Food and Nutrition Board, U.K. Expert Group of Vitamins and Minerals (draft) and U.S. Environmental Protection Agency (draft). Of interest, all of these risk assessments employed chemical-specific adjustment factors, resulting in total uncertainty factors in the range of 25-62 and estimates of tolerable intake levels ranging from 10 to 24 mg B/day. These risk assessments are particularly instructive because they all used the same critical developmental toxicity study and the same NOAEL (10 mg B/kg/day). Therefore, the primary differences among these risk assessments reside in the choice of chemical-specific adjustment factors. It is generally agreed that renal clearance is the primary determinant of B pharmacokinetic variability, both within and among species. However, the methods used to select chemical-specific adjustment factors for pharmacokinetics vary among B risk assessments. Several have estimated intraspecies pharmacokinetic variability based on glomerular filtration rates (GFR) in pregnant women. Based on the results of renal clearance studies of B, the use of GFR is scientifically appropriate to estimate the intraspecies pharmacokinetic variability in B renal clearance. B homeostasis in humans appears to be primarily regulated by the kidney, and at typical low doses in humans, there is evidence of tubular reabsorption of B in the kidneys. Human studies indicate that urinary B excretion is a sensitive indicator of recent dietary intake. The major source of B exposure in humans is consumption of fruits, vegetables, nuts and legumes, which are naturally rich in B. Human dietary consumption of B is below the estimated tolerable intake levels established in these recent risk assessments. Considering the growing evidence of the nutritional role of B, it is important to consider both the benefits and risks of B consumption. By legitimately reducing the uncertainty factor for toxicity, the margin of safety is effectively increased to protect against the possibility of insufficient dietary intake. Risk assessments of B provide valuable lessons regarding how chemical-specific adjustment factors may be selected.
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