过错在因果关系判断中的影响

过错与因果关系共同作为侵权行为的构成要件,并非彼此间毫无联系,过错对于因果关系的判断有重要影响,侵权人、受害人、第三人的过错均影响到因果关系判断,但过错并非在因果关系判断中独立发挥作用,过错须和原因力结合在一起确定侵权责任范围,这样才能更接近公平.     

Comparative Potency Method for Cancer Risk Assessment: Application to Diesel Particulate Emissions1

An estimation of the human lung cancer “unit risk” from diesel engine particulate emissions has been made using a comparative potency approach. This approach involves evaluating the tumorigenic and mutagenic potencies of the particulates from four diesel and one gasoline engine in relation to other combustion and pyrolysis products (coke oven, roofing tar, and cigarette smoke) that cause lung cancer in humans. The unit cancer risk is predicated on the linear nonthreshold extrapolation model and is the individual lifetime excess lung cancer risk from continuous exposure to 1 μg carcinogen per m³ inhaled air. The human lung cancer unit risks obtained from the epidemiologic data for coke oven workers, roofing tar applicators, and cigarette smokers were, respectively, 9.3 × 10^?4, 3.6 × 10^?4, and 2.2 × 10^?6 per μg particulate organics per m³ air. The comparative potencies of these three materials and the diesel and gasoline engine exhaust particulates (as organic extracts) were evaluated by in vivo tumorigenicity bioassays involving skin initiation and skin carcinogenicity in SENCAR mice and by the in vitro bioassays that proved suitable for this analysis: Ames Salmonella microsome bioassay, L5178Y mouse lymphoma cell mutagenesis bioassay, and sister chromatid exchange bioassay in Chinese hamster ovary cells. The relative potencies of the coke oven, roofing tar, and cigarette smoke emissions, as determined by the mouse skin initiation assay, were within a factor of 2 of those determined using the epidemiologic data. The relative potencies, from the in vitro bioassays as compared to the human data, were similar for coke oven and roofing tar, but for the cigarette smoke condensate the in vitro tests predicted a higher relative potency. The mouse skin initiation bioassay was used to determine the unit lung cancer risk for the most potent of the diesel emissions. Based on comparisons with coke oven, roofing tar, and cigarette smoke, the unit cancer risk averaged 4.4 × 10^?4. The unit lung cancer risks for the other, less potent motor-vehicle emissions were determined from their comparative potencies relative to the most potent diesel using three in vitro bioassays. There was a high correlation between the in vitro and in vivo bioassays in their responses to the engine exhaust particulate extracts. The unit lung cancer risk per μg particulates per m³ for the automotive diesel and gasoline exhaust particulates ranged from 0.20 × 10^?4 to 0.60 × 10^?4; that for the heavy-duty diesel engine was 0.02 × 10^?4. These unit risks provide the basis for a future assessment of human lung cancer risks when combined with human population exposure to automotive emissions.     

Book Reviews

Books reviewed:
Office International Des Epizooties (World Organization for Animal Health) World Animal Health in 1998, Part 1: Reports on the Animal Health Status and Disease Control Methods and Tables on Incidence of List A Diseases and Part 2: Tables on the Animal Health Status and Disease Control Methods
Peter Sedlmeier. Lawrence Erlbaum Associates, Mahwah Improving Statistical Reasoning: Theoretical Models and Practical Implications
Andrew Ford. Island Press Modeling the Environment. An Introduction to System Dynamics Modeling of Environmental Systems
Jacob I. Bregman. Lewis Publishers, Boca Raton Environmental Impact Statements, Second Edition     

神的逻各斯翅膀——亚里士多德的理论对希腊正教的辩护

亚里士多德以其"中道观"、"辩正观"、"潜能与现实"关系以及"悲剧观"对希腊正教的辩护首先体现在希腊正教教堂风格的简朴和分布的密集;其次是恩典之道上的获恩与赐恩关系;再次是在原罪上的净化与自救原则.这些辩护充分反映了基督教在异邦传播中神学巧妙地借鉴和运用西方本土化的优势资源,特别是亚里士多德的伦理学、哲学和文学等的智慧资源而构成的成功范例,即为神学安插上了飞翔的逻各斯翅膀,为基督教在异邦传播提供了强有力的理论支持.     

On a confidence interval about a parameter estimated by a ratio of normal random variables

A confidence interval is geometrically constructed about a parameter estimated by the ratio of bivariate normal random variables. The resulting confidence interval is equivalent to that of Fieller's theorem. The geometric construction shown that such intervals are conservative. Bioassay examples are used to demonstrate the technique.     

Improving Cancer Dose–Response Characterization by Using Physiologically Based Pharmacokinetic Modeling: An Analysis of Pooled Data for Acrylonitrile-Induced Brain Tumors to Assess Cancer Potency in the Rat

Historically, U.S. regulators have derived cancer slope factors by using applied dose and tumor response data from a single key bioassay or by averaging the cancer slope factors of several key bioassays. Recent changes in U.S. Environmental Protection Agency (EPA) guidelines for cancer risk assessment have acknowledged the value of better use of mechanistic data and better dose–response characterization. However, agency guidelines may benefit from additional considerations presented in this paper. An exploratory study was conducted by using rat brain tumor data for acrylonitrile (AN) to investigate the use of physiologically based pharmacokinetic (PBPK) modeling along with pooling of dose–response data across routes of exposure as a means for improving carcinogen risk assessment methods. In this study, two contrasting assessments were conducted for AN-induced brain tumors in the rat on the basis of (1) the EPA's approach, the dose–response relationship was characterized by using administered dose/concentration for each of the key studies assessed individually; and (2) an analysis of the pooled data, the dose–response relationship was characterized by using PBPK-derived internal dose measures for a combined database of ten bioassays. The cancer potencies predicted for AN by the contrasting assessments are remarkably different (i.e., risk-specific doses differ by as much as two to four orders of magnitude), with the pooled data assessments yielding lower values. This result suggests that current carcinogen risk assessment practices overestimate AN cancer potency. This methodology should be equally applicable to other data-rich chemicals in identifying (1) a useful dose measure, (2) an appropriate dose–response model, (3) an acceptable point of departure, and (4) an appropriate method of extrapolation from the range of observation to the range of prediction when a chemical's mode of action remains uncertain.     

Risk Assessment for Aflatoxin: An Evaluation Based on the Multistage Model

Lifetime cancer potency of alfatoxin was assessed based on the Yeh et al. study from China in which both aflatoxin exposure and hepatitis B prevalence were measured. This study provides the best available information for estimating the carcinogenic risk posed by aflatoxin to the U.S. population. Cancer potency of aflatoxin was estimated using a biologically motivated risk assessment model. The best estimate of aflatoxin potency was 9 (mg/kg/day)⁻¹ for individuals negative for hepatitis B and 230 (mg/kg/day)⁻¹ for individuals positive for hepatitis B.     

Combining Multivariate Bioassays: Accurate Inference Using Small Sample Asymptotics

For several independent multivariate bioassays performed at different laboratories or locations, the problem of testing the homogeneity of the relative potencies is addressed, assuming the usual slope‐ratio or parallel line assay model. When the homogeneity hypothesis holds, interval estimation of the common relative potency is also addressed. These problems have been investigated in the literature using likelihood‐based methods, under the assumption of a common covariance matrix across the different studies. This assumption is relaxed in this investigation. Numerical results show that the usual likelihood‐based procedures are inaccurate for both of the above problems, in terms of providing inflated type I error probabilities for the homogeneity test, and providing coverage probabilities below the nominal level for the interval estimation of the common relative potency, unless the sample sizes are large, as expected. Correction based on small sample asymptotics is investigated in this article, and this provides significantly more accurate results in the small sample scenario. The results are also illustrated with examples.     

Comparison of the EU T25 Single Point Estimate Method with Benchmark Dose Response Modeling for Estimating Potency of Carcinogens

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.     

How Tautological Are Interspecies Correlations of Carcinogenic Potencies?

Crouch and Wilson demonstrated a strong correlation between carcinogenic potencies in rats and mice, supporting the extrapolation from mouse to man. Bernstein et al. , however, show that the observed correlation is mainly a statistical artifact of bioassay design. Crouch et al. have a comeback. This paper will review the arguments and present some new data. The correlation is largely (but not totally) tautological, confirming results in Bernstein et al.