Research on radiation carcinogenesis requires a twofold approach. Studies of primary molecular lesions and subsequent cytogenetic changes are essential, but they cannot at present provide numerical estimates of the risk of small doses of ionizing radiations. Such estimates require extrapolations from dose, time, and age dependences of tumor rates observed in animal studies and epidemiological i...

This paper compares four alternative approaches for deriving regulatory levels for reproductive toxicants by applying them to the available data on the human spermatotoxicant 1,2-dibromo-3-chloropropane (DBCP). The alternatives examined include the Proposition 65 approach (application of a mandatory 1000-fold uncertainty factor to a no-observed-adverse-effect level [NOAEL]), the Environmental P...

Uncertainty in estimates of internal doses to can arise for a variety of reasons, which include a lack of knowledge about assumed model parameters, uncertainty in exposure conditions, paucity of measurement data, and variability between individuals. In some cases, for example, causation or epidemiological studies, it is essential to be able to quantify this uncertainty for each individual in th...

The prevailing belief for some decades has been that human radiation-related cataract occurs only after relatively high doses; for instance, the ICRP estimates that brief exposures of at least 0.5-2 Sv are required to cause detectable lens opacities and 5 Sv for vision-impairing cataracts. For protracted exposures, the ICRP estimates the corresponding dose thresholds as 5 Sv and 8 Sv, respectiv...

The Child-Specific Aggregate Cumulative Human Exposure and Dose (CACHED) framework integrates micro-level activity time series with mechanistic exposure equations, environmental concentration distributions, and physiologically-based pharmacokinetic components to estimate exposure for multiple routes and chemicals. CACHED was utilized to quantify cumulative and aggregate exposure and dose estima...

In 2014, Health Canada was approached by the Canadian Nuclear Safety Commission to conduct biodosimetry for a possible overexposure 4 y prior to assessment. Dose estimates were determined by means of two cytogenetic assays, the dicentric chromosome assay (DCA) and translocations as measured by the fluorescent in situ hybridization (FISH). As dicentrics are considered to be unstable over time, t...

Interpretation of clinical trials comparing different drug regimens for Parkinson's disease (PD) is complicated by the different dose intensities used: higher doses of levodopa and, possibly, other drugs produce better symptomatic control but more late complications. To address this problem, conversion factors have been calculated for antiparkinsonian drugs that yield a total daily levodopa equ...

Radon concentration alone may not be an adequate surrogate to measure for lung cancer risk in all residential radon epidemiologic lung cancer studies. The dose delivered to the lungs per unit radon exposure can vary significantly with exposure conditions. These dose-effectiveness variations can be comparable to spatial and temporal factor variations in many situations. New technologies that use...

During development of a drug, typically the choice of dose is based on a Phase II dose-finding trial, where selected doses are included with placebo. Two common statistical dose-finding methods to analyze such trials are separate comparisons of each dose to placebo (using a multiple comparison procedure) or a model-based strategy (where a dose-response model is fitted to all data). The first ap...

OBJECTIVE The present study was undertaken to investigate the pharmacokinetics of metronidazole in pregnant patients with bacterial vaginosis. METHODS Twenty patients received metronidazole (Flagyl ®, Pfizer, 235 East 42nd Street, NY, NY 10017) oral dose 500 mg twice a day for 3 consecutive days. Pharmacokinetic analyses of metronidazole were performed after a single oral dose on the morning ...