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Benchmark Dose (benchmark + dose)

Distribution by Scientific Domains

Mathematics and Statistics	66%
Medical Sciences	33%

Selected Abstracts

Dose,time,response modeling of longitudinal measurements for neurotoxicity risk assessment

ENVIRONMETRICS, Issue 6 2005
Yiliang Zhu
Abstract Neurotoxic effects are an important non-cancer endpoint in health risk assessment and environmental regulation. Neurotoxicity tests such as neurobehavioral screenings using a functional observational battery generate longitudinal dose,response data to profile neurological effects over time. Analyses of longitudinal neurotoxicological data have mostly relied on analysis of variance; explicit dose,time,response modeling has not been reported in the literature. As dose,response modeling has become an increasingly indispensible component in risk assessment as required by the use of benchmark doses, there are strong interests in and needs for appropriate dose,response models, effective model-fitting techniques, and computation methods for benchmark dose estimation. In this article we propose a family of dose,time,response models, illustrate statistical inference of these models in conjunction with random-effects to quantify inter-subject variation, and describe a procedure to profile benchmark dose across time. We illustrate the methods through a dataset from a US/EPA experiment involving the FOB tests on rats administered to a single dose of triethyl tin (TET). The results indicate that the existing functional observational battery data can be utilized for dose,response and benchmark dose analyses and the methods can be applied in general settings of neurotoxicity risk assessment. Copyright © 2005 John Wiley & Sons, Ltd. [source]

Estimation of the number of working hours critical for the development of mental and physical fatigue symptoms in Japanese male workers,application of benchmark dose method

AMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 3 2007
Yasushi Suwazono PhD
Abstract Background To clarify the influence of working hours on subjective fatigue symptoms and obtain the critical dose (number of hours) to determine the number of permissible working hours, we calculated the benchmark dose (BMD) and the 95% lower confidence limit on BMD (BMDL) of working hours for subjective mental and fatigue symptoms using multivariate logistic regression. Methods Self-administered questionnaires were distributed to all 843 male daytime workers aged ,60 years in a single chemical factory, and 715 provided complete replies. The odds ratios of daily working hours were determined using positive findings of the Self-rating Depression Scale and 8 subscales of the Cumulative Fatigue Symptom Index as dependent variables, and other potential covariates as independent variables. Using significant parameters for the working hours and those for other covariates, the BMD and BMDL (BMD/BMDL) values were calculated for corresponding dependent variables. The benchmark response (BMR) was set at 5% or 10%. Results The BMDL with a BMR of 5% was shown to be 9.6,11.6 hr per day, which corresponds to 48,58 working hours per week and 36,78 overtime hours per month. Conclusions These results suggest that special attention should be paid to the workers whose working hours exceed these BMD/BMDL values. Am. J. Ind. Med. 50: 173,182, 2007. © 2007 Wiley-Liss, Inc. [source]

Quantitative Risk Assessment for Multivariate Continuous Outcomes with Application to Neurotoxicology: The Bivariate Case

BIOMETRICS, Issue 3 2005
Zi-Fan Yu
Summary The neurotoxic effects of chemical agents are often investigated in controlled studies on rodents, with multiple binary and continuous endpoints routinely collected. One goal is to conduct quantitative risk assessment to determine safe dose levels. Such studies face two major challenges for continuous outcomes. First, characterizing risk and defining a benchmark dose are difficult. Usually associated with an adverse binary event, risk is clearly definable in quantal settings as presence or absence of an event; finding a similar probability scale for continuous outcomes is less clear. Often, an adverse event is defined for continuous outcomes as any value below a specified cutoff level in a distribution assumed normal or log normal. Second, while continuous outcomes are traditionally analyzed separately for such studies, recent literature advocates also using multiple outcomes to assess risk. We propose a method for modeling and quantitative risk assessment for bivariate continuous outcomes that address both difficulties by extending existing percentile regression methods. The model is likelihood based; it allows separate dose,response models for each outcome while accounting for the bivariate correlation and overall characterization of risk. The approach to estimation of a benchmark dose is analogous to that for quantal data without the need to specify arbitrary cutoff values. We illustrate our methods with data from a neurotoxicity study of triethyl tin exposure in rats. [source]

Confidence Bands for Low-Dose Risk Estimation with Quantal Response Data

BIOMETRICS, Issue 4 2003
Obaid M. Al-Saidy
Summary. We study the use of simultaneous confidence bands for low-dose risk estimation with quantal response data, and derive methods for estimating simultaneous upper confidence limits on predicted extra risk under a multistage model. By inverting the upper bands on extra risk, we obtain simultaneous lower bounds on the benchmark dose (BMD). Monte Carlo evaluations explore characteristics of the simultaneous limits under this setting, and a suite of actual data sets are used to compare existing methods for placing lower limits on the BMD. [source]

Carcinogenicity of acetaldehyde in alcoholic beverages: risk assessment outside ethanol metabolism

ADDICTION, Issue 4 2009
Dirk W. Lachenmeier
ABSTRACT Aims In addition to being produced in ethanol metabolism, acetaldehyde occurs naturally in alcoholic beverages. Limited epidemiological evidence points to acetaldehyde as an independent risk factor for cancer during alcohol consumption, in addition to the effects of ethanol. This study aims to estimate human exposure to acetaldehyde from alcoholic beverages and provide a quantitative risk assessment. Methods The human dietary intake of acetaldehyde via alcoholic beverages was estimated based on World Health Organization (WHO) consumption data and literature on the acetaldehyde contents of different beverage groups (beer, wine, spirits and unrecorded alcohol). The risk assessment was conducted using the European Food Safety Authority's margin of exposure (MOE) approach with benchmark doses obtained from dose,response modelling of animal experiments. Life-time cancer risk was calculated using the T25 dose descriptor. Results The average exposure to acetaldehyde from alcoholic beverages was estimated at 0.112 mg/kg body weight/day. The MOE was calculated to be 498, and the life-time cancer risk at 7.6 in 10 000. Higher risk may exist for people exposed to high acetaldehyde contaminations, as we have found in certain unrecorded alcohol beverages in Guatemala and Russia, for which we have demonstrated possible exposure scenarios, with risks in the range of 1 in 1000. Conclusions The life-time cancer risks for acetaldehyde from alcoholic beverages greatly exceed the usual limits for cancer risks from the environment set between 1 : 10 000 and 1 : 1 000 000. Alcohol consumption has thus been identified as a direct source of acetaldehyde exposure, which in conjunction with other sources (food flavourings, tobacco) results in a magnitude of risk requiring intervention. An initial public health measure could be to reduce the acetaldehyde content in alcoholic beverages as low as technologically possible, and to restrict its use as a food flavour additive. [source]