Types of Integration in Risk Assessment and Management,And Why They Are Needed

Risk-based decision making requires that the decision makers and stakeholders are informed of all risks that are potentially significant and relevant to the decision. The International Programme on Chemical Safety of the World Health Organization has developed a framework for integrating the assessment of human health and ecological risks. However, other types of integration are needed to support particular environmental decisions. They are integration of exposure and effects, of multiple chemicals and other hazardous agents, of multiple routes of exposure, of multiple endpoints, multiple receptors, multiple spatial and temporal scales, a product's life cycle, management alternatives, and socioeconomics with risk assessment. Inclusion of all these factors in an integrated assessment could lead to paralysis by analysis. Therefore, it is important that assessors be cognizant of the decision process and that decision makers and those who will influence the decision (stakeholders) be involved in planning the assessment to ensure that the degree of integration is necessary and sufficient.     

International programme on chemical safety (IPCS) environmental health criteria on boron human health risk assessment

The International Program on Chemical Safety (IPCS), a collaborative program of the United Nations Environment Program, the International Labour Organization (ILO), and the World Health Organization (WHO), includes the Environmental Health Criteria (EHC) Program inaugurated in 1973 by WHO. These EHC are integrated evaluations of the human health and environmental risks from exposure to specific chemicals carried out by a group of international scientists. Boron (B) was evaluated at an IPCS Task Group (TG) convened in November 1996. All TGs are convened under WHO rules and procedures. These procedures relate the overall process used to prepare an EHC including transparency of the process, conflict of interest, the roles of Members and Observers, and the conduct of the TG. The scope and purpose of an EHC, for an element such as B, and its possible role in national and international chemical safety programs will be discussed. In the early 1990s, countries asked that IPCS request TGs to prepare, where data permit, health-based guidance values (GVs) (both total daily intake and to recommend health-based guidelines for various environmental media). This final evaluation in an EHC reflects the collective consensus view of the TG Members. To foster the use of consistent methodology by TGs, IPCS prepared in 1994 an EHC on the methodology for the preparation of GVs for human exposure limits (EHC 170). In developing their final evaluation, TGs have been asked to consider using this methodology. This was done by the TG on B, and a total daily intake for humans of 0.4 mg/kg body wt was derived from animal studies of reproductive and developmental effects in rodents and pharmacokinetic data from both animals and humans. The application of the methodology described in EHC 170 regarding choice of critical effect and uncertainty factors will be discussed.     

Framework for the Integration of Health and Ecological Risk Assessment

The World Health Organization's International Programme on Chemical Safety (IPCS), the Organization for Economic Cooperation and Development (OECD), and the U.S. Environmental Protection Agency have developed a collaborative partnership to foster integration of assessment approaches for human health and ecological risks. This paper presents the framework developed by that group. Integration provides coherent expressions of assessment results, incorporates the interdependence of humans and the environment, uses sentinel organisms, and improves the efficiency and quality of assessments relative to independent human health and ecological risk assessments. The paper describes how integration can occur within each component of risk assessment, and communicates the benefits of integration at each point. The goal of this effort is to promote the use of this internationally accepted guidance as a basis for harmonization of risk assessment.     

生物多样性科学前沿

由国际生物科学联盟（ＩＵＢＳ）在１９９１年首先提出,至今已由其它５个重要国际组织或项目（ＳＣＯＰＥ、ＵＮＥＳＣＯ,ＩＣＳＵ,ＩＧＢＰ－ＧＣＴＥ及ＩＵＭＳ）共同主持的ＤＩＶＥＲＳＩＴＡＳ是迄今生物多样性科学研究唯一的国际性项目。１９９６年７月,科学指导委员会草拟了本阶段新的操作计划,并于同年８月在ＩＵＢＳ执行委员会上讨论。操作计划详述了１０个组成方面的内容,其中５个为核心组成部分,其它５个为特别目标     

Vicia faba chromosomal aberration assay

A collaborative study involving laboratories in six countries was initiated under the sponsorship of the International Programme on Chemical Safety (IPCS) to determine the sensitivity, efficiency and reliability of the Vicia faba root tip meristem chromosomal aberration assay using a standardized protocol. The six Laboratories that participated in this study were located in the Slovak Republic, India, Japan, Poland, Sweden and the USA. All laboratories adhered to a standardized protocol for the Vicia faba chromosomal aberartion assay. Four coded chemicals, azidoglycerol (AG), N-methyl-N-nitrosourea (MNU), sodium azide (NaN₃) and maleic hydrazide (MH) were tested with the Vicia faba chromosomal aberration assay. Of the four chemicals, three (MH, AG and MNU) were found to be clastogenic and gave a concentration related response. However, the results of NaN₃ were equivocal which might be explained by the stability of NaN₃. The conclusions from this study suggest that the Vicia faba chromosomal aberration bioassay is an efficient and reliable short-term bioassay for the rapid screening of chemicals for clastogenicity.     

Climate Change-related Health Impacts in the Hindu Kush–Himalayas

Our goal was to identify the climate change-related health risks and vulnerable populations specific to the mountainous regions of the Hindu Kush–Himalayas. We reviewed published information of the likely health consequences of climate change in mountain regions, especially the findings of a workshop for countries in the Hindu Kush–Himalaya region, organized by the World Health Organization, World Meteorological Organization, United Nations Environment Programme, and United Nations Development Programme. The main climate-related risks in the Hindu Kush–Himalaya region include the expansion of vector-borne diseases as pathogens take advantage of new habitats in altitudes that were formerly unsuitable. Diarrheal diseases could become more prevalent with changes in freshwater quality and availability. More extreme rainfall events are likely to increase the number of floods and landslides with consequent death and injuries. A unique risk is sudden floods from high glacier lakes, which cause substantial destruction and loss of life. Because glaciers are the main source of freshwater for upland regions and downstream countries, the long-term reduction in annual glacier snowmelt is expected to heighten existing water insecurity in these areas. Climate change also is bringing some benefits to mountain populations, including milder winters and longer growing seasons. Populations in mountain regions have unique combinations of vulnerabilities to climate change. The extent of the health impacts experienced will depend on the effectiveness of public health efforts to identify and implement low-cost preparedness and response measures, and on the speed at which emissions of greenhouse gas emissions can be reduced.     

An introduction and study design

Under the sponsorship of the International Programme on Chemical Safety (IPCS), 17 laboratories from diverse regions of the world participated in evaluating the utility of four plant bioassays for detecting genetic hazards of environmental chemicals. The bioassays included in this collaborative study were: Arabidopsis thaliana embryo and chlorophyll assay and Tradescantia stamen hair assay, Tradescantia paludosa micronucleus assay and Vicia Faba root tip assay. Four to six laboratories participated in the performance of each of the bioassays. All laboratories participating in a particular bioassay were supplied with uniform plant material as well as standardized protocol. Five direct acting water soluble test chemicals, i.e. maleic hydrazide, methyl nitrosourea, ethyl methanesulfonate, sodium azide and azidoglycerol, were selected for this study. The study was designed to be completed in three phases. Ethyl methanesulfonate was used as a positive control and has already been reported earlier (Sandhu et al., 1991). The data from the remaining four chemicals used for the evaluation of four plant test systems in the first phase of the collaborative study are reported in this issue.     

Ecologically sustainable chemical recommendations for agricultural pest control?

Effective pest control remains an essential part of food production, and it is provided both by chemicals and by natural enemies within agricultural ecosystems. These methods of control are often in conflict because of the negative impact of chemicals on natural enemies. There are already well-established approaches such as those provided by the International Organization for Biological and Integrated Control-Pesticides and Beneficial Organisms for testing, collecting, and publishing information on responses of natural enemies to chemicals based on laboratory responses of specific organisms; however, these tests do not assess the cumulative impact of chemical inputs across an entire season or consider impacts on the complex communities of natural enemies that can provide effective pest control on a farm. Here, we explore the potential of different approaches for assessing the impact of chemicals on agricultural ecosystems and we propose a simple metric for sustainable chemical use on farms that minimizes overall impact on beneficial groups. We suggest ways in which the effectiveness of metrics can be extended to include persistence and habitat features. Such metrics can assist farmers in developing targets for sustainable chemical use as demonstrated in the viticultural industry.     

Replacing the Default Values of 10 With Data-Derived Values: A Comparison of Two Different Data-Derived Uncertainty Factors for Boron

A “safe” or sub-threshold dose is often estimated for oral toxicity of substances in order to protect humans from adverse health effects. This dose is referred to by several terms: reference dose (RfD), tolerable daily intake (TDI), and acceptable daily intake (ADI). Similarly, tolerable concentration (TC), and reference concentration (RfC) are commonly used terms for a “safe” concentration for inhalation. The process of deriving these doses generally involves identifying a no observed, or lowest observed adverse effect level (NOAEL or LOAEL) in animals, or humans, and application of uncertainty factors to account for the extrapolation from laboratory animals to humans and/or from an average human to a sensitive human. Public health agencies have begun to consider using a data derived approach, which uses available toxicokinetic and toxicodynamic data in the determination of uncertainty factors, rather than relying on the standard default values. Recently two different tolerable daily intake risk values were derived by two different World Health Organization (WHO) work groups. The International Programme on Chemical Safety, and the Working Group on Chemical Substances in Drinking Water both used the approach developed by Renwick (1993); however, the two groups interpreted and used the available data differently. The result was a difference of over twofold in the total uncertainty factor used. This review compares and contrasts the two approaches used by these WHO work groups.     

Helminth-infected patients with malaria: a low profile transmission hub?

The scale-up of malaria control efforts in recent years, coupled with major investments in malaria research, has produced impressive public health impact in a number of countries and has led to the development of new tools and strategies aimed at further consolidating malaria control goals. As a result, there is a growing need for the malaria policy setting process to rapidly review increasing amounts of evidence. The World Health Organization Global Malaria Programme, in keeping with its mandate to set evidence-informed policies for malaria control, has convened the Malaria Policy Advisory Committee as a mechanism to increase the timeliness, transparency, independence and relevance of its recommendations to World Health Organization member states in relation to malaria control and elimination. The Malaria Policy Advisory Committee, composed of 15 world-renowned malaria experts, will meet in full twice a year, with the inaugural meeting scheduled for 31 January to 2 February 2012 in Geneva. Policy recommendations, and the evidence to support them, will be published within two months of every meeting as part of an open access Malaria Journal thematic series. This article is a prelude to that series and provides the global malaria community with the background and overview of the Committee and its terms of reference.     

Approaches for Integrated Risk Assessment

Recognizing the need to enhance the effectiveness and efficiency of risk assessments globally, the World Health Organization's International Programme on Chemical Safety, the U.S. Environmental Protection Agency, the European Commission, and the Organization for Economic Cooperation and Development developed a collaborative partnership to foster integration of assessment approaches used to evaluate human health and ecological risks. The objectives of this effort included: improving understanding of the benefits of integration, identifying obstacles to the integration process, and engaging key agencies, organizations, and scientific societies to promote integration. A framework with supporting documentation was developed to describe an approach for integration. Four case studies were constructed to illustrate how integrated risk assessments might be conducted for chemical and nonchemical stressors. The concepts and approaches developed in the project were evaluated in an international workshop. The goal of this effort was international acceptance of guidance for integrated risk assessment.     

The Economic Benefits Resulting from the First 8 Years of the Global Programme to Eliminate Lymphatic Filariasis (2000–2007)

Background

Between 2000–2007, the Global Programme to Eliminate Lymphatic Filariasis (GPELF) delivered more than 1.9 billion treatments to nearly 600 million individuals via annual mass drug administration (MDA) of anti-filarial drugs (albendazole, ivermectin, diethylcarbamazine) to all at-risk for 4–6 years. Quantifying the resulting economic benefits of this significant achievement is important not only to justify the resources invested in the GPELF but also to more fully understand the Programme''s overall impact on some of the poorest endemic populations.

Methodology

To calculate the economic benefits, the number of clinical manifestations averted was first quantified and the savings associated with this disease prevention then analyzed in the context of direct treatment costs, indirect costs of lost-labor, and costs to the health system to care for affected individuals. Multiple data sources were reviewed, including published literature and databases from the World Health Organization, International Monetary Fund, and International Labour Organization

Principal Findings

An estimated US$21.8 billion of direct economic benefits will be gained over the lifetime of 31.4 million individuals treated during the first 8 years of the GPELF. Of this total, over US$2.3 billion is realized by the protection of nearly 3 million newborns and other individuals from acquiring lymphatic filariasis as a result of their being born into areas freed of LF transmission. Similarly, more than 28 million individuals already infected with LF benefit from GPELF''s halting the progression of their disease, which results in an associated lifetime economic benefit of approximately US$19.5 billion. In addition to these economic benefits to at-risk individuals, decreased patient services associated with reduced LF morbidity saves the health systems of endemic countries approximately US$2.2 billion.

Conclusions/Significance

MDA for LF offers significant economic benefits. Moreover, with favorable program implementation costs (largely a result of the sustained commitments of donated drugs from the pharmaceutical industry) it is clear that the economic rate of return of the GPELF is extremely high and that this Programme continues to prove itself an excellent investment in global health.     

Onchocerciasis in West Africa after 2002: a challenge to take up

Initially planned for a 20 year life time, the Onchocerciasis Control Programme in West Africa (OCP) will have finally continued its activities for nearly three decades (vector control alone from 1975 to 1989, then vector control and/or therapeutic treatment until 2002). Although onchocerciasis is no longer a problem of public health importance nor an obstacle to socio-economic development in the OCP area, the control of this filariasis is not over because OCP never aimed at eradication, neither of the parasite (Onchocerca volvulus), nor of its vector (Simulium damnosum s.l.). In 2003, the eleven Participating countries of OCP will take over the responsibility of carrying out the residual activities of monitoring and the control of this disease. This mission is of great importance because any recrudescence of the transmission could lead in the long run to the reappearance of the clinical signs of onchocerciasis, if not its most serious manifestations. For epidemiological and operational reasons, and given the disparity in national health policies and infrastructures, the capacities of the countries to take over the residual activities of monitoring and control of onchocerciasis are very unequal. Indeed, the interventions to be carried out are very different from one country to another and the process of integrating the residual activities into the national health systems is not taking place at the same pace. This inequality among the countries vis-a-vis the challenges to be met does not, however, prejudge the epidemiological situation after 2002 whose evolution will also depend on the effectiveness of the provisions made before that date by OCP, then after 2002, by the Regional Office for Africa of the World Health Organization which is currently setting up a sub-regional multidisease surveillance centre.     

Gestational exposure to cigarette smoke imperils the long-term physical and mental health of offspring

BACKGROUND: In this study, we sought to understand whether prenatal exposure to cigarette smoke would be associated with increased offspring hospitalization through age 22 years for various physical and mental health diagnoses. METHODS: We used multivariate logistic regression to investigate the relationship between gestational exposure to cigarette smoke and offspring hospitalization for physical and mental health conditions based on International Classification of Diseases (ICD; World Health Organization) diagnoses. RESULTS: When controlling for parental psychiatric status, maternal somatic health, socioeconomic status, parity, and maternal age, youth born to mothers who smoked six or more cigarettes per day were more likely to have experienced hospitalization for neuroses (OR, 1.97), diseases of the nervous system (i.e., neurological disorders) (OR, 1.47), respiratory infections (OR, 1.28), accidents (OR, 1.44), infections (OR, 1.54), undiagnosed symptoms (OR, 1.65), and total admissions (OR, 1.48). Female offspring prenatally exposed were more likely to have experienced hospitalization for obstetric complications (OR, 2.94). No association was found for the remaining categories analyzed: blood disorders, skin diseases, psychoses, metabolic/endocrine disease, circulatory disease, digestive disease, disease of the skeletal/muscular system, physical anomalies, neoplasms, and genital/urinary disease. CONCLUSIONS: This is the first study to investigate the impact of gestational exposure to cigarette smoke on global measures of somatic and physical health in offspring. This study adds to the literature by demonstrating that smoking during pregnancy increases offspring risk for additional health outcomes not previously recognized in the literature, and that the effect of smoking during pregnancy persists throughout the developmental period. The possibility that these findings are related to lifestyle markers or smoke exposure during childhood should also be considered.     

Introducing the UNEP/SETAC methodological sheets for subcategories of social LCA

Purpose  

In May 2009, the Guidelines for Social Life Cycle Assessment of Products (the Guidelines) were launched at the occasion of the International Organization for Standardization (ISO) 26000 (Social Responsibility) meeting in Quebec City, Canada. Developed by a United Nations Environment Programme/Society of Environmental Toxicology and Chemistry (“UNEP/SETAC”) Life Cycle Initiative project group on Social Life Cycle Assessment (S-LCA), the Guidelines provide a framework to assess social impacts across product life cycles. A year later, the Methodological Sheets for the Subcategories of Social LCA (“the Methodological Sheets”) are being made available to support practitioners engaging in the field. The Methodological Sheets provide practical guidance for conducting S-LCA case studies by offering consistent, yet flexible assistance.     

Health and safety implications of exposure to electromagnetic fields in the frequency range 300 Hz to 10 MHz.

An international seminar on health effects of exposure to electromagnetic fields (EMF) in the frequency range from 300 Hz to 10 MHz (referred to as the Intermediate Frequency (IF) range) was held in Maastricht, Netherlands, on 7-8 June 1999. The seminar, organized under the International EMF Project, was sponsored jointly by the World Health Organization (WHO), the International Commission on Non-Ionizing Radiation Protection (ICNIRP), and the Government of the Netherlands. This report does not attempt to summarize all of the material presented at the conference, but focuses on sources of exposure, biophysical and dosimetric considerations pertinent to extrapolating biological data from other frequency ranges to IF and identifies potential health concerns and needs for developing exposure guidelines. This paper is based on presentations at the conference and reports of working groups consisting of the speakers and other experts. It concludes with recommendations for further research aimed at improving health risk assessments in this frequency range.     

A review of the risk of contamination of semen and embryos during cryopreservation and measures to limit cross-contamination during banking to prevent disease transmission in ET practices

This review summarizes pertinent data and opinions regarding the potential hazard of disease transmission through cryopreserved and banked embryos in liquid nitrogen (LN). Special attention is given to the survival of pathogens in LN, new vitrification methods, sterility of LN, risks associated with the use of straws and cryovials, and LN dewars including dry shippers. It was experimentally demonstrated that cross-contamination between LN and embryos may occur, when infectious agents are present in LN and embryos are not protected by a sealed container. It is important, therefore, to prevent direct contact of embryos with LN during cryopreservation and their banking. This includes the usage of hermetically sealed, high-quality, shatter-proof freezing containers and/or the application of a secondary enclosure such as “double bagging or straw in straw.” A periodic disinfection of cryo-dewars should be considered as an additional precaution to diminish the potential for inadvertent cross-contamination. It might be advisable to use separate LN dewars to quarantine embryos derived from infected donors of valuable genotype or from unknown health status, extinction-threatened species. Nevertheless, in summary, it has been concluded that over 25 yr with no direct evidence of disease transmission by transferred cryopreserved human and animal embryos, that the present cryopreservation technology is sanitary sound, with the stipulation that biocontainment measures recommended by the International Embryo Transfer Society (IETS) and the World Organization for Animal Health - Office International des Epizooties (OIE), are strictly followed.     

The global impact of income inequality on health by age: an observational study

Objectives To explore whether the apparent impact of income inequality on health, which has been shown for wealthier nations, is replicated worldwide, and whether the impact varies by age.Design Observational study. Setting 126 countries of the world for which complete data on income inequality and mortality by age and sex were available around the year 2002 (including 94.4% of world human population).Data sources Data on mortality were from the World Health Organization and income data were taken from the annual reports of the United Nations Development Programme.Main outcome measures Mortality in 5-year age bands for each sex by income inequality and income level.Results At ages 15-29 and 25-39 variations in income inequality seem more closely correlated with mortality worldwide than do variations in material wealth. This relation is especially strong among the poorest countries in Africa. Mortality is higher for a given level of overall income in more unequal nations.Conclusions Income inequality seems to have an influence worldwide, especially for younger adults. Social inequality seems to have a universal negative impact on health.     

Effect of reducing the top concentration used in the in vitro chromosomal aberration test in CHL cells on the evaluation of industrial chemical genotoxicity

A current concern with in vitro mammalian cell genotoxicity testing is the high frequency of false or misleading positive results caused in part by the past use of excessively high test concentrations. A dataset of 249 industrial chemicals used in Japan and tested for genotoxicity was analyzed. Of these, 116 (46.6%) were positive in the in vitro chromosomal aberration (CA) test, including 6 that were positive only at test concentrations >10mM. There were 59 CA-positive chemicals at test concentrations ≤ 1mM. At >1mM, 51 chemicals were CA-positive, including 13 Ames-positive chemicals, which were therefore not "missed" by the test battery. Thus, 38 potentially positive chemicals would not have been detected in the test battery if the top test concentration was limited to 1mM in CA test. Analysis of the relevance of CA results on the 38 missed chemicals was conducted based on a weight of evidence approach, including evaluations of effects of extreme culture conditions (low pH, high toxicity, or precipitation), in silico structural alert analysis, in vivo genotoxicity and carcinogenicity test data (where available), mode of action, or information from closely related chemicals. After an exhaustive review, there were four chemicals with some concern for human health risk assessment, nine with minimal concern, and the remaining 25 with negligible concern. We apply different top concentrations to the 38 missed chemicals to identify the most accurate approach for predicting the genotoxicity of industrial chemicals. Of these 2mM or 1mg/mL, whichever is higher, was the most effective in detecting these chemicals, i.e., relatively higher (8/13) or lower (17/25) detection among 13 chemicals with some or minimal concern, or 25 with negligible concern, respectively. Lower top concentration limits, 1mM or 0.5mg/mL, whichever is higher, are not as effective (2/13) for detecting these chemicals with concern. Therefore, we conclude 2mM or 1mg/mL, whichever is higher, would be an appropriate top concentration limit for testing industrial chemicals for chromosome damage.