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Biomedical subjects

Kenny Crump

Publications and source records attributed to Kenny Crump.

4 recordsLinked to original sources
PubMed2004

Relative potencies and additivity of perchlorate, thiocyanate, nitrate, and iodide on the inhibition of radioactive iodide uptake by the human sodium iodide symporter.

The presence of perchlorate (ClO(4) (-)) in some U.S. drinking water supplies has raised concern about potential adverse thyroidal health effects, because ClO(4) (-) is known to competitively inhibit iodide uptake at the sodium iodide symporter (NIS). Humans are nutritionally and environmentally exposed to other competitive inhibitors of iodide uptake, including thiocyanate (SCN(-)) and nitrate (NO(3) (-)). The joint inhibiting effects of these three anions was studied by exposing Chinese hamster ovary cells stably expressing human NIS to varying concentrations of each anion separately, and in combination, and conducting measurements of (125)I(-) uptake. The entire data set was fit to a single Hill equation using maximum likelihood. The relative potency of ClO(4) (-) to inhibit (125)I(-) uptake at the NIS was found to be 15, 30 and 240 times that of SCN(-), I(-), and NO(3) (-) respectively on a molar concentration basis, with no evidence of synergism. These results are consistent with a common mode of action by these anions of simple competitive interaction, in which a concentration of any one of ClO(4) (-) SCN(-), and NO(3) (-), occurring either individually or as part of a mixture of the three anions, is indistinguishable from a concentration or dilution of either one of the remaining two ions in inhibiting iodine uptake at the NIS.

Algorithms↗
PubMed2003

Dose-response and risk assessment of airborne hexavalent chromium and lung cancer mortality.

This study evaluates the dose-response relationship for inhalation exposure to hexavalent chromium [Cr(VI)] and lung cancer mortality for workers of a chromate production facility, and provides estimates of the carcinogenic potency. The data were analyzed using relative risk and additive risk dose-response models implemented with both Poisson and Cox regression. Potential confounding by birth cohort and smoking prevalence were also assessed. Lifetime cumulative exposure and highest monthly exposure were the dose metrics evaluated. The estimated lifetime additional risk of lung cancer mortality associated with 45 years of occupational exposure to 1 microg/m3 Cr(VI) (occupational exposure unit risk) was 0.00205 (90%CI: 0.00134, 0.00291) for the relative risk model and 0.00216 (90%CI: 0.00143, 0.00302) for the additive risk model assuming a linear dose response for cumulative exposure with a five-year lag. Extrapolating these findings to a continuous (e.g., environmental) exposure scenario yielded an environmental unit risk of 0.00978 (90%CI: 0.00640, 0.0138) for the relative risk model [e.g., a cancer slope factor of 34 (mg/kg-day)-1] and 0.0125 (90%CI: 0.00833, 0.0175) for the additive risk model. The relative risk model is preferred because it is more consistent with the expected trend for lung cancer risk with age. Based on statistical tests for exposure-related trend, there was no statistically significant increased lung cancer risk below lifetime cumulative occupational exposures of 1.0 mg-yr/m3, and no excess risk for workers whose highest average monthly exposure did not exceed the current Permissible Exposure Limit (52 microg/m3). It is acknowledged that this study had limited power to detect increases at these low exposure levels. These cancer potency estimates are comparable to those developed by U.S. regulatory agencies and should be useful for assessing the potential cancer hazard associated with inhaled Cr(VI).

Air Pollutants, Occupational↗
PubMed2002

Critical issues in benchmark calculations from continuous data.

The benchmark dose (BMD) is a dose that causes a specified low level of additional risk and is estimated using a statistical dose-response analysis. Regulatory agencies are using a statistical lower bound on the BMD in the place of the NOAEL for establishing exposure limits. However, there are still several issues regarding the BMD for which no clear consensus has emerged, particularly with respect to calculation of BMD from continuous response data. These include: (1) how to define the BMD from continuous data so that they are comparable to BMD derived from binary data, (2) what dose-response models and levels of additional risk should be used to calculate the BMD. The "hybrid" approach (Gaylor and Slikker, 1990; Crump, 1995) expresses the BMD from continuous data in terms that are directly comparable to those obtained using binary data. Several features of the hybrid approach are examined, with the emphasis on application to epidemiological data. The effect on the BMD of converting continuous data to binary form is quantified. Model uncertainty is explored, and the need for controlling this uncertainty by restricting the class of allowable models is demonstrated. Control data, which are often not available in epidemiological studies, are shown to have a limited effect upon the BMD so long as the model for the mean response is linear or convex. Such models are also biologically plausible, at least at low doses. Based on these and other considerations, suggestions are made for selecting a model for applying the hybrid approach and for selecting the level of additional risk on which to base the BMD.

Algorithms↗