Biomedical subjects

Sean M Hays

Publications and source records attributed to Sean M Hays.

5 recordsLinked to original sources

PubMed2006

Risk assessment for children exposed to decabromodiphenyl (oxide) ether (Deca) in the United States.

Decabromodiphenyl (oxide) ether (Deca) is a widely used brominated flame retardant in the United States predominantly in the hard-plastic housings of consumer electronics and in flame-retarded backing on textiles used in furniture. A child-specific exposure assessment of Deca was performed for the US Environmental Protection Agency's Voluntary Children's Chemical Evaluation Program (VCCEP). The VCCEP guidance for a tier 1 exposure assessment requires that a screening-level assessment be conducted using currently available data and conservative assumptions. For Deca, relevant exposure pathways considered were general environmental exposures (e.g., exposures to contaminated soil, dust, air, and food), breast milk exposures, inhalation of Deca-containing particulates in air, and mouthing Deca-containing consumer products. For each of these scenarios, a mid-range and upper estimate of age-appropriate intakes were calculated. The calculated intakes indicate that, despite the uncertainties, children appear to be exposed to Deca at levels at least 1 order of magnitude, with most being several orders of magnitude, below the National Academy of Sciences reference dose for Deca of 4 mg/kg/d. This analysis indicates that, using the available data, current levels of Deca in the United States are unlikely to represent an adverse health risk for children.

Child↗

PubMed2005

Do children have increased susceptibility for developing secondary acute myelogenous leukemia?

This study was undertaken to evaluate the effects of age on a child's susceptibility to developing leukemia following exposure to known leukemogenic agents. The clinical literature describing the risk of developing acute myelogenous leukemia (AML) following treatment with alkylating agents or topoisomerase reactive drugs (known leukemogens) was used as a basis for this investigation. Based on this preliminary assessment, the age of the child does not appear to be an independent variable for risk following treatment with either class of drug. Although the number of studies and cases was very small, the available scientific and medical literature does not support the hypothesis that children will necessarily have an altered susceptibility or increased risk of developing chemotherapy-induced AML.

Adult↗

PubMed2005

Concentration-dependent TCDD elimination kinetics in humans: toxicokinetic modeling for moderately to highly exposed adults from Seveso, Italy, and Vienna, Austria, and impact on dose estimates for the NIOSH cohort.

Serial measurements of serum lipid 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) concentrations in 36 adults from Seveso, Italy, and three patients from Vienna, Austria, with initial serum lipid TCDD concentrations ranging from 130 to 144,000 ppt, were modeled using a modified version of a previously published toxicokinetic model for the distribution and elimination of dioxins. The original model structure accounted for a concentration-dependent increase in overall elimination rate for TCDD due to nonlinear distribution of TCDD to the liver (secondary to induction of the binding protein CYP1A2), from which elimination takes place via a first-order process. The original model structure was modified to include elimination due to lipid partitioning of TCDD from circulation into the large intestine, based on published human data. We optimized the fit of the modified model to the data by varying the hepatic elimination rate parameter for each of the 39 people. The model fits indicate that there is significant interindividual variability of TCDD elimination efficiency in humans and also demonstrate faster elimination in men compared to women, and in younger vs. older persons. The data and model results indicate that, for males, the mean apparent half-life for TCDD (as reflected in changes in predicted serum lipid TCDD level) ranges from less than 3 years at serum lipid levels above 10,000 ppt to over 10 years at serum lipid levels below 50 ppt. Application of the model to serum sampling data from the cohort of US herbicide-manufacturing workers assembled by the National Institute of Occupational Safety and Health (NIOSH) indicates that previous estimates of peak serum lipid TCDD concentrations in dioxin-exposed manufacturing workers, based on first-order back-extrapolations with half-lives of 7-9 years, may have underestimated the maximum concentrations in these workers and other occupational cohorts by several-fold to an order of magnitude or more. Such dose estimates, based on a single sampling point decades after last exposure, are highly variable and dependent on a variety of assumptions and factors that cannot be fully determined, including interindividual variations in elimination efficiency. Dose estimates for these cohorts should be re-evaluated in light of the demonstration of concentration-dependent elimination kinetics for TCDD, and the large degree of uncertainty in back-calculated dose estimates should be explicitly incorporated in quantitative estimates of TCDD's carcinogenic potency based on such data.

Accidents, Occupational↗

PubMed2003

Dioxin risks in perspective: past, present, and future.

The United States Environmental Protection Agency (USEPA) and other U.S. and international agencies have focused extensive efforts on the evaluation of the potential health risks of exposures to chlorinated dioxins (PCDDs), furans (PCDFs), and related dioxin-like polychlorinated biphenyls (PCBs). Extensive regulatory efforts over the past 20 years have also been made to control emissions of these compounds and thus to reduce exposures in the general population. This paper reviews the available information on temporal trends in emissions, environmental levels, intake levels through foods, and human body burdens of dioxins. This paper also provides an overview and comparison of recent hazard assessments for dioxins from U.S. and international agencies. Available data on emissions, environmental and food levels, and human body burdens of dioxins in the general population indicate a several-fold reduction in exposures and body burdens in the general population over the three decades from 1970 to 2000. U.S. and international hazard assessments concur on certain aspects, but disagree on fundamental issues including the likelihood of a threshold for carcinogenic dose-response and the degree of safety factors needed in deriving a protective exposure limit. These disagreements have significant consequences for interpreting the potential health risks of current background dioxin exposure levels. However, whatever the degree of health risk that may be associated with current background exposures, the general population is experiencing several-fold lower exposures, and, therefore, lower health risks, currently compared to 30 years ago. In light of the dramatic declines in exposure already observed, further efforts to reduce exposures through attempts to control emissions or food levels should be carefully evaluated to understand the likely efficacy of the efforts and the relative costs and benefits.

Animals↗

PubMed2002

Temporal trends in human TCDD body burden: decreases over three decades and implications for exposure levels.

Data on lipid levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the general population in the United States, Canada, Germany, and France over the past 30 years were compiled from the literature. Mean lipid levels of TCDD exhibited a steady decrease by nearly a factor of 10 over this time period, with lipid-adjusted TCDD levels in 2000 about 2 parts per trillion (ppt). Pharmacokinetic modeling using a one-compartment model indicated that absorbed intake levels of TCDD must have decreased by more than 95% from levels in 1972 to result in the observed decrease in human lipid levels, with the bulk of this decrease occurring before 1980. Based on this modeling and the pharmacokinetic properties of TCDD in humans, we conclude that mean levels of TCDD in the general population are likely to decrease further over the next 15 years, to between 0.5 and 1 ppt, even if intake levels do not decrease further. Fewer data over a shorter time period are available for other dioxin and furan congeners in human lipid, but these data indicate substantial decreases as well, with general population TEQ lipid levels currently at least fourfold lower than in 1970 and still decreasing. Food sampling data are limited, but support these trends.

Absorption↗