Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Communicating Information on Eruptions and Their Impacts from the Earliest Times Until the Late Twentieth Century

Volcanoes hold a fascination for human beings and, before they were recorded by literate observers, eruptions were portrayed in art, were recalled in legends and became incorporated into religious practices: being viewed as agents of punishment, bounty or intimidation depending upon their state of activity and the culture involved. In the Middle East the earliest depiction of an eruption is a wall painting dating from the Neolithic at Çatal Hüyük and the earliest record dates from the third millennium BCE. Knowledge of volcanoes increased over time. In some parts of the world knowledge of eruptions was passed down by oral transmission, but as far as written records were concerned, in the first century CE only 9 volcanoes in the Mediterranean region were recognised, together with Mount Cameroon in West Africa. In the next 1000 years the list grew by 17, some 14 of these volcanoes being in Japan. The first recorded eruptions in Indonesia occurred in 1000 and 1006, and volcanoes in newly settled Iceland increased the number to just 48 in 1380 CE. After this the list continued to increase, with important regions such as New Zealand and Hawaii only being added in the past 200 years. Only from 1900 did the rate of growth decline significantly (Simkin et al. 1981: 23; Simkin, 1993 Siebert et al. 2011; Simkin, 1993), but it is sobering to recall that in the twentieth century major eruptions have occurred from volcanoes that were considered inactive or extinct examples including: Mount Lamington - Papua New Guinea, 1951; Mount Arenal - Costa Rica, 1968 and Nyos - Cameroon, 1986. Although there are instances where the human impact of historical eruptions have been compiled - with examples including the 1883 eruption of Krakatau (Simkin and Fiske (1983) and 1943 -1952 eruption of Parícutin (Luhr and Simkin, 1993) - these are exceptions and there remains a significant gap in knowledge about both the short and long-term effects on societies of major eruptions which occurred before the 1980s. Following a broad review the chapter provides a discussion of the ways in which information has been collected, compiled and disseminated from the earliest times until the 1980s in two case study areas: the Azores Islands (Portugal) and southern Italy. In Italy information on eruptions stretches back to prehistoric times and has become progressively better known over more than 2,000 years of written history, yet even here there remain significant gaps in the record even for events that took place between 1900 and 1990. In contrast, located in the middle of the Atlantic, the Azores have been isolated for much of their history and illustrate the difficulties involved in using indigenous sources to compile, not only assessments of impact, but also at a more basic level a complete list of historical events with accurate dates

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety ‘Mode of Action’ framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/ mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety ‘Mode of Action’ framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Mining academies as centers of geological research and education in Europe between the 18th and 19th centuries

The importance of the early activities of the mining academies for the scientific development of the Earth sciences is generally accepted by historians of geology, mining and metallurgy, but it needs more support from new detailed researches on primary sources. The teaching programs of these of education, where also distinguised scientists were employed, did not include only the technical disciplines traditionally connected to mining, but also scientific courses, which included mineralogy, lithology and geology. This paper intends to offer an overview of this historiographical question within the European context.La importancia de las primeras actividades de las escuelas de minas para el desarrollo científico de las Ciencias de la Tierra está generalmente aceptada por los historiadores de la geología, la minería y la metalurgia, pero necesita más apoyo de nuevas investigaciones detalladas sobre las fuentes primarias. Los programas de enseñanza de estos centros, que emplearon también a distinguidos científicos, no sólo incluyeron las disciplinas técnicas tradicionalmente relacionadas con la minería, sino que también se desarrollaron cursos científicos, que contemplaron la mineralogía, la geología y la litología. El presente trabajo pretende ofrecer una visión general de esta cuestión historiográfica en el contexto europeo

The "classification" of mountains in eighteenth century Italy and the lithostratigraphical theory of Giovanni Arduino (1714-1795)

During the 18th century, scientific literature devoted to the Earth sciences documented a significant increase in the study of the composition and formation of mountains and above all their stratigraphical sequence. The diverse and widely ranging philosophical theories of the late 17th century on the origin of the Earth were gradually replaced by new concepts based on field research on both a local and regional scale. This new approach analyzed the lithology and the fossil content of the rocks, the geomorphology of the area and in some cases helped to determine the chronological sequence of mountain formation. Nicolaus Steno's idea of superimposition of strata (1667-69) was followed by most of the late 18th century scholars in Earth sciences, who developed sub-divisions of mountains from the point of view of their formation, but which also included a classification of the rocks. These sub-divisions supported the idea of relative chronology of the formation sequence of the studied strata: the most recent or the most ancient formation could be deduced from their position in the sequence but also from their external lithological features. In this context the role of scientific terminology, which was gradually established in 18th century geological science, became very important: the terms "primary" (or \u201cprimitive\u201d), "secondary" and "tertiary" were used for indicating the categories of mountains but also for stratigraphical units. In the second half of the 18th century, the work of Giovanni Arduino contributed decisively to the development of basic lithostratigraphic \u2018classification\u2019 of rocks and mountain building. His lithological studies, a result of twenty years of fieldwork in the mountains and hills of the Venetian and Tuscan regions, were also supported by a specialized knowledge in mining. The new \u2018classification\u2019 into four basic units called "ordini" (1760) was based only on lithology (without using paleontological indicators) and included different rock types which formed three kinds of mountains and one kind of plains in a regular chronological order: "Primary" (underlain by \u201cprimeval\u201d schist considered by him to be the oldest rock type), "Secondary" and "Tertiary". A \u201cfourth\u201d and younger lithological unit included only alluvial deposits. Arduino's system is still regarded by the geological world as being one of the starting points for modern stratigraphy

Quelques réflexions sur les instructions scientifiques destinées aux géologues voyageurs aux dix-huitième et dix-neuvième siècles

International audiencePendant le dix-huitième siècle, l'augmentation constante des recherches sur la structure de la surface de la Terre et ses divers composants - roches, minerais, fossiles - fut strictement liée à l'expérience du voyage (Guntau, 1984, p.27-29 ; Stafford, 1984 ; Ellenberger, 1994, p. 169-170). (...

"Volcanic travels" and the development of volcanology in 18th century Europe

The aim of this paper is to provide an overview of the different ways of travelling through a volcanic region and studying a volcano - in order to describe its lithological, mineralogical and geological features - particularly in the second half of the 18th century. The increasing amount of data collected in the field during these travels, as well as the suggested interpretations of the volcanic phenomena in the Mediterranean region, also contributed to the European debate on the formation and on the age of the Earth's surface