An Adjustment Factor for Mode-of-Action Uncertainty with Dual-Mode Carcinogens: The Case of Naphthalene-Induced Nasal Tumors in Rats

The U.S. Environmental Protection Agency (USEPA) guidelines for cancer risk assessment recognize that some chemical carcinogens may have a site-specific mode of action (MOA) involving mutation and cell-killing-induced hyperplasia. The guidelines recommend that for such dual MOA (DMOA) carcinogens, judgment should be used to compare and assess results using separate "linear" (genotoxic) versus "nonlinear" (nongenotoxic) approaches to low-level risk extrapolation. Because the guidelines allow this only when evidence supports reliable risk extrapolation using a validated mechanistic model, they effectively prevent addressing MOA uncertainty when data do not fully validate such a model but otherwise clearly support a DMOA. An adjustment-factor approach is proposed to address this gap, analogous to reference-dose procedures used for classic toxicity endpoints. By this method, even when a "nonlinear" toxicokinetic model cannot be fully validated, the effect of DMOA uncertainty on low-dose risk can be addressed. Application of the proposed approach was illustrated for the case of risk extrapolation from bioassay data on rat nasal tumors induced by chronic lifetime exposure to naphthalene. Bioassay data, toxicokinetic data, and pharmacokinetic analyses were determined to indicate that naphthalene is almost certainly a DMOA carcinogen. Plausibility bounds on rat-tumor-type-specific DMOA-related uncertainty were obtained using a mechanistic two-stage cancer risk model adapted to reflect the empirical link between genotoxic and cytotoxic effects of the most potent identified genotoxic naphthalene metabolites, 1,2- and 1,4-naphthoquinone. Bound-specific adjustment factors were then used to reduce naphthalene risk estimated by linear extrapolation (under the default genotoxic MOA assumption), to account for the DMOA exhibited by this compound.     

内部审计在企业风险管理中的作用

社会经济中不确定因素的增加导致企业风险的复杂化。由现代企业会计丑闻引发的企业风险管理近年来已成为备受关注的焦点问题。理论界和事务界已开始重视对风险导向内部审计,将其作为预防企业风险的必要手段研究,但其尚处于不成形的探讨阶段。本文着重分析了风险管理与内部审计的关系,并由此引出风险管理有效性的讨论。     

环境公平与新农村建设

生态环境的保护与改善是新农村建设的重要内容。近些年,环境公平问题在农村社会凸显,严重威胁着农村社会的环境安全和可持续发展,成为新农村建设中的薄弱环节和制约因素。从城乡关系、群体关系和代际关系等几个层面分析当前农村社会存在的环境公平问题,只有通过实现城乡一体化管理,加大农村环境的监管力度;加快实施生态补偿制度;加强农村环境教育和法制教育,提高农民的环境意识和维权意识;进行制度创新,发展农村循环经济等一系列措施,才能保障农村环境公平的实现。     

实现环境污染负外部性的内在化

在当今中国,靠一般号召和一般行政手段不能根本解决环境污染问题。环境经济学、产权经济学启示我们,必须努力做到环境污染负外部性的内在化,应该特别地加强资源、环境法制保障体系的建设。     

当代环境伦理学对旅游道德的深层启示

旅游是人与自然交往的一种重要形式。从当代环境伦理学的哲学反思和理论创见出发,可从四个方面提升旅游道德境界:热爱大自然,大自然的善良公民;珍爱生命多样性,尊重其他生命的价值;克服个体小我,实现生态大我;反对破坏环境的行为,维护生态环境和谐。     

COSO新框架下企业内部控制与风险管理的思考

内部控制是全面风险管理的必要环节,其动力来自企业对风险的认识和管理。对此,我们必须尽快转换长期以来固化的观念和思维定式,努力构建体现全面风险管理的内部控制新机制,赋予内部控制新的内容。     

Bridging the gap between ecological research and land use policy: The North Sonoran Collaboration

A key factor in bridging the gap between ecological research and public land use policy is translating information from the language of research into the language of public policy making. Creating effective translations of research is often beyond the skills of urban planners and environmental researchers individually, and thus collaboration between the two is needed. Examples of such translation and partnerships can be found in the projects of an interdisciplinary group coined the North Sonoran Collaborative. This group consists of Phoenix, AZ, USA city staff, Arizona State University faculty, graduate students, and staff, and people from other local private companies and government agencies. The group, through its collaboration, has sponsored a series of environmental research efforts and translated those into successful land use planning activities and policies. The focus of the collaboration is the northern, largely undeveloped portion of the city of Phoenix, Arizona. This group has pursued three principles: desert ecosystems should be protected, a diversity of development should be pursued, and a sense of community should be created in new developments. This paper discusses this unique approach to planning and how it has proven effective in responding to the local communities needs quickly.     

商业银行利率风险管理技术综述

一、引言(一)现实背景从2000年9月21日起,我国利率市场化改革进入实质性阶段,预计三年内完成。利率市场化是一场系统性的金融革命,必将对经济金融领域的方方面面产生重要影响。商业银行应积极采取措施,应对利率市场化将带来的一系列风险。近几年,我国发行了大量的国债和金融债,     

风险导向审计模式演进中的经济学释义

中国注册会计师协会“会协(2004)69号”文关于审计风险相关准则征求意见稿的推出,意味着协会“独立审计准则建设的重点是以现代风险导向审计思想为基础,拟订和修订审计风险准则,以强化会员在执业过程中的风险意识和质量意识,降低审计风险”这一行业建设战略思想进一步得到落实。但总的来讲,风险导向型审计在我国还处于萌芽状态,理论和实务上都不够成熟,如何科学应用风险导向审计方法,目前还是一片空白,这正是本文研究的出发点。     

金融市场内在脆弱性原因分析

金融市场具有内生的脆弱性,其产生原因与信贷市场不同。作为特殊经营行业,与实体经济相比,金融产品具有明显的特殊性,特别是在网络金融时代。这也决定着金融市场内生脆弱性产生的原因,具体说来,包括以下几点:金融产品的供给和需求几乎是完全弹性的;金融产品的虚拟性;金融产品交易的跨期性以及金融市场结构的特殊性等。