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  • 1
    Digitale Medien
    Digitale Medien
    350 Main Street , Malden , MA 02148 , USA , and 9600 Garsington Road , Oxford OX4 2DQ , UK . : Blackwell Publishing, Inc.
    Risk analysis 23 (2003), S. 0 
    ISSN: 1539-6924
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Energietechnik
    Notizen: An occupational risk assessment for manganese (Mn) was performed based on benchmark dose analysis of data from two epidemiological studies providing dose-response information regarding the potential neurological effects of exposure to airborne Mn below the current Occupational Safety and Health Administration (OSHA) Permissible Exposure Level (PEL) of 5 mg Mn/m3. Based on a review of the scientific evidence regarding the toxicity of Mn, it was determined that the most appropriate measure of exposure to airborne Mn for the subclinical effects measured in these studies is recent (rather than historical or cumulative) concentration of Mn in respirable (rather than total) particulate. For each of the studies analyzed, the individual exposure and response data from the original study had been made available by the investigators. From these two studies benchmark concentrations calculated for eight endpoints ranged from 0.09 to 0.27 mg Mn/m3. From our evaluation of these results, and considering the fact that the subtle, subclinical effects represented by the neurological endpoints tested in these studies do not represent material impairment, we believe an appropriate occupational exposure guideline for manganese would be in the range of 0.1 to 0.3 mg Mn/m3, based on the respirable particulate fraction only, and expressed as an 8-hour time-weighted average.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    350 Main Street , Malden , MA 02148 , USA , and 9600 Garsington Road , Oxford OX4 2DQ , UK . : Blackwell Publishing, Inc.
    Risk analysis 25 (2005), S. 0 
    ISSN: 1539-6924
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Energietechnik
    Notizen: While quantitative estimates of risk have been a standard practice in cancer risk assessment for many years, no similar practice is evident in noncancer risk assessment. We use two recent examples involving methylmercury and arsenic to illustrate the negative impact of this discrepancy on risk communication and cost-benefit analysis. We argue for a more balanced treatment of cancer and noncancer risks and suggest an approach for reaching this goal.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 3
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Risk analysis 18 (1998), S. 0 
    ISSN: 1539-6924
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Energietechnik
    Notizen: Estimates were made of the numbers of liver carcinogens in 390 long-term bioassays conducted by the National Toxicology Program (NTP). These estimates were obtained from examination of the global pattern of p-values obtained from statistical tests applied to individual bioassays. Representative estimates of the number of liver carcinogens (90% confidence interval in parentheses) obtained in our analysis compared to NTP's determination are as follows: female rats—49 (23, 76), NTP = 30; male rats—88 (59, 116), NTP = 35; female mice—131 (105, 157), NTP = 81; male mice—100 (73, 126), NTP = 61; overall—166 (135, 197), NTP = 108. The estimator from which these estimates were obtained is biased low by an unknown amount. Consequently, this study provides persuasive evidence of the existence of more rodent liver carcinogens than were identified by the NTP.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 4
    Digitale Medien
    Digitale Medien
    350 Main Street , Malden , MA 02148 , USA , and 9600 Garsington Road , Oxford OX4 2DQ , UK . : Blackwell Publishing, Inc.
    Risk analysis 25 (2005), S. 0 
    ISSN: 1539-6924
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Energietechnik
    Notizen: In this article, we describe a straightforward method for solving the probability of at least one malignant cell by time t, and the associated hazard function, in the general (i.e., nonhomogeneous) two-stage Moolgavkar-Venzon-Knudson (MVK) model of cancer. The method consists of solving four coupled ordinary differential equations derived from the Kolmogorov backward equations for this process. The relationship of this method to previously proposed solutions is discussed.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 5
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Risk analysis 18 (1998), S. 0 
    ISSN: 1539-6924
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Energietechnik
    Notizen: Since substantial bias can result from assigning some type of mean exposure to a group, risk assessments based on epidemiological data should avoid the grouping of data whenever possible. However, ungrouped data are frequently unavailable, and the question arises as to whether an arithmetic or geometric mean is the most appropriate summary measure of exposure. It is argued in this paper that one should use the type of mean for which the total risk that would result if every member of the population was exposed to the mean level is as close as possible to the actual total population risk. Using this criterion an arithmetic mean is always preferred over a geometric mean whenever the dose response is convex. In each of several data sets examined in this paper for which the dose response was not convex, an arithmetic mean was still preferred based on this criterion.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 6
    ISSN: 1539-6924
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Energietechnik
    Notizen: The T25 single-point estimate method of evaluating the carcinogenic potency of a chemical, which is currently used by the European Union (EU) and is denoted the EU approach, is based on the selection of a single dose in a chronic bioassay with an incidence rate that is significantly higher than the background rate. The T25 is determined from that single point by a linear extrapolation or interpolation to the chronic dose (in mg/kg/day), at which a 25% increase in the incidence of the specified tumor type is expected, corrected for the background rate. Another method used to obtain a carcinogenic potency value based on a 25% increase in incidence above the background rate is the estimation of a T25 derived from a benchmark dose (BMD) response model fit to the chronic bioassay data for the specified tumor type. A comparison was made between these two methods using 276 chronic bioassays conducted by the National Toxicology Program. In each of the 2-year bioassays, a tumor type was selected based on statistical and biological significance, and both EU T25 and BMD T25 estimates were determined for that end point. In addition, simulations were done using underlying cumulative probability distributions to examine the effect of dose spacing, the number of animals per dose group, the possibility of a dose threshold, and variation in the background incidence rates on the EU T25 and BMD estimates. The simulations showed that in the majority of cases the EU T25 method underestimated the true T25 dose and overestimated the carcinogenic potency. The BMD estimate is generally less biased and has less variation about the true T25 value than the EU estimate.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 7
    ISSN: 1539-6924
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Energietechnik
    Notizen: An analysis of the uncertainty in guidelines for the ingestion of methylmercury (MeHg) due to human pharmacokinetic variability was conducted using a physiologically based pharmacokinetic (PBPK) model that describes MeHg kinetics in the pregnant human and fetus. Two alternative derivations of an ingestion guideline for MeHg were considered: the U.S. Environmental Protection Agency reference dose (RfD) of 0.1 pg/kg/day derived from studies of an Iraqi grain poisoning episode, and the Agency for Toxic Substances and Disease Registry chronic oral minimal risk level (MRL) of 0.5 pglkglday based on studies of a fisheating population in the Seychelles Islands. Calculation of an ingestion guideline for MeHg from either of these epidemiological studies requires calculation of a dose conversion factor (DCF) relating a hair mercury concentration to a chronic MeHg ingestion rate. To evaluate the uncertainty in this DCF across the population of U.S. women of child-bearing age, Monte Carlo analyses were performed in which distributions for each of the parameters in the PBPK model were randomly sampled lo00 times. The 1st and 5th percentiles of the resulting distribution of DCFs were a factor of 1.8 and 1.5 below the median, respectively. This estimate of variability is consistent with, but somewhat less than, previous analyses performed with empirical, one-compartment pharmacokinetic models. The use of a consistent factor in both guidelines of 1.5 for pharmacokinetic variability in the DCF, and keeping all other aspects of the derivations unchanged, would result in an RfD of 0.2 pglkglday and an MRL of 0.3 pglkglday.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 8
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Risk analysis 11 (1991), S. 0 
    ISSN: 1539-6924
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Energietechnik
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 9
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Risk analysis 8 (1988), S. 0 
    ISSN: 1539-6924
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Energietechnik
    Notizen: Twenty-three chemicals were selected for comparison of the carcinogenic potencies estimated from epidemiological data to those estimated from animal carcinogenesis bioassays. The chemicals were all those for which reasonably strong evidence of carcinogenicity could be found in humans or animals and for which suitable data could be obtained for quantifying carcinogenic potencies in both humans and animals. Many alternative methods of analyzing the bioassay data were investigated. Almost all of the methods yielded potency estimates that were highly correlated with potencies estimated from epidemiological data; correlations were highly statistically significant (p 〈 0.001), with the corresponding correlation coefficients ranging as high as 0.9. These findings provide support for the general use of animal data to evaluate carcinogenic potential in humans and also for the use of animal data to quantify human risk.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 10
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Risk analysis 8 (1988), S. 0 
    ISSN: 1539-6924
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Energietechnik
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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