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  • 11
    Electronic Resource
    Electronic Resource
    On Summarizing Group Exposures in Risk Assessment: Is an Arithmetic Mean or a Geometric Mean More Appropriate? (1998)
    Oxford, UK : Blackwell Publishing Ltd
    Risk analysis 18 (1998), S. 0 
    Details
    ISSN: 1539-6924
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1539-6924.1998.tb01296.x
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  • 12
    Electronic Resource
    Electronic Resource
    Estimates of the Number of Liver Carcinogens in Bioassays Conducted by the National Toxicology Program (1998)
    Oxford, UK : Blackwell Publishing Ltd
    Risk analysis 18 (1998), S. 0 
    Details
    ISSN: 1539-6924
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1539-6924.1998.tb01297.x
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  • 13
    Electronic Resource
    Electronic Resource
    Comparison of the EU T25 Single Point Estimate Method with Benchmark Dose Response Modeling for Estimating Potency of Carcinogens (2001)
    Boston, USA and Oxford, UK : Blackwell Publishers Inc.
    Risk analysis 21 (2001), S. 0 
    Details
    ISSN: 1539-6924
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/0272-4332.214141
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  • 14
    Electronic Resource
    Electronic Resource
    Evaluation of the Uncertainty in an Oral Reference Dose for Methylmercury Due to Interindividual Variability in Pharmacokinetics (1999)
    Springer
    Risk analysis 19 (1999), S. 547-558 
    Details
    ISSN: 1539-6924
    Keywords: MeHg ; pharmacokinetics ; PBPK model ; variability ; risk assessment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract 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 μg/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 μg/kg/day based on studies of a fish-eating 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 1000 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 μg/kg/day and an MRL of 0.3 μg/kg/day.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007017116171
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  • 15
    Electronic Resource
    Electronic Resource
    Transient behaviour of the single loop solute cycling model of the renal medulla (1978)
    Springer
    Bulletin of mathematical biology 40 (1978), S. 273-300 
    Details
    ISSN: 1522-9602
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Mathematics
    Notes: Abstract Transient solutions are developed for the buildup of a concentration gradient in the single loop solute cycling model of the renal medulla. The “pump” from ascending limb to descending limb is considered in both unsaturated and completely saturated modes of operation. Both analytic solutions and semianalytic solutions obtained from inverting Laplace transforms are considered. The classic representation of concentration buildup by the multiplication process is compared with calculated profiles. The “single effect” is found to vary both in time and space.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02461602
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  • 16
    Electronic Resource
    Electronic Resource
    Influence of Prenatal Mercury Exposure Upon Scholastic and Psychological Test Performance: Benchmark Analysis of a New Zealand Cohort (1998)
    Springer
    Risk analysis 18 (1998), S. 701-713 
    Details
    ISSN: 1539-6924
    Keywords: Benchmark ; mercury ; risk assessment ; epidemiology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract This paper presents benchmark (BMD) calculations and additional regression analyses of data from a study in which scores from 26 scholastic and psychological tests administered to 237 6- and 7-year-old New Zealand children were correlated with the mercury concentration in their mothers' hair during pregnancy. The original analyses of five test scores found an association between high prenatal mercury exposure and decreased test performance, using category variables for mercury exposure. Our regression analyses, which utilized the actual hair mercury level, did not find significant associations between mercury and children's test scores. However, this finding was highly influenced by a single child whose mother's mercury hair level (86 mg/kg) was more than four times that of any other mother. When that child was omitted, results were more indicative of a mercury effect and scores on six tests were significantly associated with the mothers' hair mercury level. BMDs calculated from five tests ranged from 32 to 73 mg/kg hair mercury, and corresponding BMDLs (95% lower limits on BMDs) ranged from 17 to 24 mg/kg. When the child with the highest mercury level was omitted, BMDs ranged from 13 to 21 mg/kg, and corresponding BMDLs ranged from 7.4 to 10 mg/kg.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/B:RIAN.0000005917.52151.e6
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