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Biomedical subjects

K Mahaffey

Publications and source records attributed to K Mahaffey.

4 recordsLinked to original sources

Derivation of U.S. EPA's oral Reference Dose (RfD) for methylmercury.

Mercury (Hg) cycles in the environment through a series of complex chemical and physical transformations that occur in air, soils, and water bodies. One component of the environmental mercury cycle is the formation of methylmercury (MHg) primarily by aquatic and marine microorganisms and the accumulation of MHg in foodwebs, particularly in piscivorous species. Human consumption of piscivorous fish and other piscivorus animals is the most common pathway of exposure to MHg. For non-carcinogenic toxic endpoints, the U.S. EPA typically develops a Reference Dose (RfD). This is generally interpreted to be a concentration of a chemical which can be consumed on a daily basis over a lifetime without expectation of adverse effect. There is substantial evidence in both animal and humans that MHg is a neurotoxicant in the adult and the child as well as a developmental neurotoxicant for the fetus. Epidemics of MHg poisoning in Japan and Iraq have resulted from high-dose exposures to MHg. In these epidemics adults, children, nursing infants and fetuses were affected by MHg. The epidemics demonstrate that neurotoxicity is the health effect of greatest concern and that effects on the developing human nervous system apparently occur at lower exposures than those affecting the adult nervous system. We describe how the data from the Iraqi MHg epidemic were used to derive the current RfD of 0.1 microgram/Kgbw/day (U.S. EPA, 1995;).

Administration, Oral↗

Characterization of risks posed by combustor emissions.

Risk characterization is the final step of the risk assessment process as practiced in the U.S. EPA. In risk characterization, the major scientific evidence and "bottom-line" results from the other components of the risk assessment process, hazard identification, dose-response assessment, and exposure assessment, are evaluated and integrated into an overall conclusion about the risks posed by a given situation. Risk characterization is also an iterative process; the results of a specific step may require re-evaluation or additional information to finalize the risk assessment process. Risks posed by atmospheric emissions are an example of an involuntary human health risk which typically receives a great deal of public attention. Characterization of the risks posed by atmospheric emissions typically requires the use of mathematical models to evaluate: 1) the environmental fate of emitted pollutants, 2) exposures to these pollutants, and 3) human dose-response. Integration of these models results in quantitative risk estimates. The confidence in a quantitative risk estimate is examined by evaluating uncertainty and variability within individual risk assessment components. Variability arises from the true heterogeneity in characteristics within a population or an event; on the other hand, uncertainty represents lack of knowledge about the true value used in a risk estimate. U.S. EPA's 1997 Mercury Study will illustrate some aspects of the risk characterization process as well as the uncertainty and variability encountered in the risk assessment process.

Air Pollutants↗

Lead and osteoporosis: mobilization of lead from bone in postmenopausal women.

Although it has been known that humans accumulate lead in bone, mineralized tissue has been considered primarily as a sequestering compartment and not as a site of toxic action for lead. However, experimental data indicate that bone lead can be released during conditions of demineralization, such as pregnancy and lactation. We have examined lead status in women, before and after menopause, using the NHANES II dataset compiled between 1976 and 1980. In 2981 black and white women there was a highly significant increase in both whole blood and calculated plasma lead concentration after menopause. The results indicate that bone lead is not an inert storage site for absorbed lead. Moreover, lead may interact with other factors in the course of postmenopausal osteoporosis, to aggravate the course of the disease, since lead is known to inhibit activation of vitamin D, uptake of dietary calcium, and several regulatory aspects of bone cell function. The consequences of this mobilization may also be of importance in assessing the risks of maternal lead exposure to fetal and infant health.

Adult↗

Absence of seasonal variation in serum concentrations of 1,25-dihydroxyvitamin D despite a rise in 25-hydroxyvitamin D in summer.

The serum concentrations of the vitamin D metabolites 25-hydroxyvitamin D2 (25OHD2), 25-hydroxyvitamin D3 (25OHD3), and 1,25-dihydroxyvitamin D (calcitriol) have been measured in normal subjects whose ages varied from 18 months to 35 yr. Samples were obtained in all months of the year in order to assess the effects of season on serum concentration. During the months of April to September, 25OHD3 levels are higher than in the winter months. No seasonal variation in the 25OHD2 or calcitriol serum concentration was observed. Age-related differences in 25OHD2 and D3 concentrations did not exist. The levels of calcitriol are higher in adolescence and increase from 35 +/- 19 pg/ml (SD) at 1.5-10 yr of age to 54 +/- 21 pg/ml at 10-20 yr of age. In young adults, the levels fall again to 28 +/- 16 pg/ml. Accordingly, despite a seasonal variation in the precursor of calcitriol, the levels of this most active metabolite of vitamin D do not change in relation to sunlight exposure. This lack of seasonal variation is further evidence of the tight feedback regulation of calcitriol.

25-Hydroxyvitamin D 2↗