Evidence on the Human Health Effects of Low-Level Methylmercury Exposure

Background: Methylmercury (MeHg) is a known neuro-toxicant. Emerging evidence indicates it may have adverse effects on the neuro-logic and other body systems at common low levels of exposure. Impacts of MeHg exposure could vary by individual susceptibility or be confounded by bene-ficial nutrients in fish containing MeHg. Despite its global relevance, synthesis of the available literature on low-level MeHg exposure has been limited

Chemical carcinogenicity revisited 2: Current knowledge of carcinogenesis shows that categorization as a carcinogen or non-carcinogen is not scientifically credible

Abstract Developments in the understanding of the etiology of cancer have undermined the 1970s concept that chemicals are either "carcinogens" or "non-carcinogens". The capacity to induce cancer should not be classified in an inflexible binary manner as present (carcinogen) or absent (non-carcinogen). Chemicals may induce cancer by three categories of mode of action: direct interaction with DNA or DNA replication including DNA repair and epigenetics; receptor-mediated induction of cell division; and non-specific induction of cell division. The long-term rodent bioassay is neither appropriate nor efficient to evaluate carcinogenic potential for humans and to inform risk management decisions. It is of questionable predicitiveness, expensive, time consuming, and uses hundreds of animals. Although it has been embedded in practice for over 50 years, it has only been used to evaluate less than 5% of chemicals that are in use. Furthermore, it is not reproducible because of the probabilisitic nature of the process it is evaluating combined with dose limiting toxicity, dose selection, and study design. The modes of action that lead to the induction of tumors are already considered under other hazardous property categories in classification (Mutagenicity/Genotoxicity and Target Organ Toxicity); a separate category for Carcinogenicity is not required and provides no additional public health protection

Chemical carcinogenicity revisited 3: Risk assessment of carcinogenic potential based on the current state of knowledge of carcinogenesis in humans

Abstract Over 50 years, we have learned a great deal about the biology that underpins cancer but our approach to testing chemicals for carcinogenic potential has not kept up. Only a small number of chemicals has been tested in animal-intensive, time consuming, and expensive long-term bioassays in rodents. We now recommend a transition from the bioassay to a decision-tree matrix that can be applied to a broader range of chemicals, with better predictivity, based on the premise that cancer is the consequence of DNA coding errors that arise either directly from mutagenic events or indirectly from sustained cell proliferation. The first step is in silico and in vitro assessment for mutagenic (DNA reactive) activity. If mutagenic, it is assumed to be carcinogenic unless evidence indicates otherwise. If the chemical does not show mutagenic potential, the next step is assessment of potential human exposure compared to the threshold for toxicological concern (TTC). If potential human exposure exceeds the TTC, then testing is done to look for effects associated with the key characteristics that are precursors to the carcinogenic process, such as increased cell proliferation, immunosuppression, or significant estrogenic activity. Protection of human health is achieved by limiting exposures to below NOEALs for these precursor effects. The decision tree matrix is animal-sparing, cost effective, and in step with our growing knowledge of the process of cancer formation

Chemical carcinogenicity revisited 1: A unified theory of carcinogenicity based on contemporary knowledge

Abstract Developments in the understanding of the etiology of cancer have profound implications for the way the carcinogenicity of chemicals is addressed. This paper proposes a unified theory of carcinogenesis that will illuminate better ways to evaluate and regulate chemicals. In the last four decades, we have come to understand that for a cell and a group of cells to begin the process of unrestrained growth that is defined as cancer, there must be changes in DNA that reprogram the cell from normal to abnormal. Cancer is the consequence of DNA coding errors that arise either directly from mutagenic events or indirectly from cell proliferation especially if sustained. Chemicals that act via direct interaction with DNA can induce cancer because they cause mutations which can be carried forward in dividing cells. Chemicals that act via non-genotoxic mechanisms must be dosed to maintain a proliferative environment so that the steps toward neoplasia have time to occur. Chemicals that induce increased cellular proliferation can be divided into two categories: those which act by a cellular receptor to induce cellular proliferation, and those which act via non-specific mechanisms such as cytotoxicity. This knowledge has implications for testing chemicals for carcinogenic potential and risk management

Which Fish Should I Eat? Perspectives Influencing Fish Consumption Choices

Background: Diverse perspectives have influenced fish consumption choices

A perspective on the measurement of time in plant disease epidemiology

The growth and development of plant pathogens and their hosts generally respond strongly to the temperature of their environment. However, most studies of plant pathology record pathogen/host measurements against physical time (e.g. hours or days) rather than thermal time (e.g. degree-days or degree-hours). This confounds the comparison of epidemiological measurements across experiments and limits the value of the scientific literature

The Multisite Violence Prevention Project: Impact of a Universal School-Based Violence Prevention Program on Social-Cognitive Outcomes

This study evaluated the impact of a universal school-based violence prevention program on social-cognitive factors associated with aggression and nonviolent behavior in early adolescence. The effects of the universal intervention were evaluated within the context of a design in which two cohorts of students at 37 schools from four sites (N=5,581) were randomized to four conditions: (a) a universal intervention that involved implementing a student curriculum and teacher training with sixth grade students and teachers; (b) a selective intervention in which a family intervention was implemented with a subset of sixth grade students exhibiting high levels of aggression and social influence; (c) a combined intervention condition; and (d) a no-intervention control condition. Short-term and long-term (i.e., 2-year post-intervention) universal intervention effects on social-cognitive factors targeted by the intervention varied as a function of students' pre-intervention level of risk. High-risk students benefited from the intervention in terms of decreases in beliefs and attitudes supporting aggression, and increases in self-efficacy, beliefs and attitudes supporting nonviolent behavior. Effects on low-risk students were in the opposite direction. The differential pattern of intervention effects for low- and high-risk students may account for the absence of main effects in many previous evaluations of universal interventions for middle school youth. These findings have important research and policy implications for efforts to develop effective violence prevention programs