Bentivoglio, Italy
Bentivoglio, Italy

Time filter

Source Type

Mandrioli D.,Ramazzini Institute
Environmental Health Perspectives | Year: 2016

Background: The most essential goal of medicine and public health is to prevent harm (primum non nocere). This goal is only fully achieved with primary prevention, which requires us to identify and prevent harms prior to human exposure through research and testing that does not involve human subjects. For that reason, public health policies place considerable reliance on nonhuman toxicological studies. However, toxicology as a field has often not produced efficient and timely evidence for decision making in public health. In response to this, the U.S. National Research Council called for the adoption of evidence-based methods and systematic reviews in regulatory decision making. The U.S. Environmental Protection Agency (EPA), the Food and Drug Administration (FDA), and the European Food Safety Agency (EFSA) have recently endorsed these methods in their assessments of safety and risk. Objectives: In this commentary we summarize challenges and problems in current practices in toxicology as applied to decision making. We compare these practices with the principles and methods utilized in evidence-based medicine and health care, with emphasis on the record of the Cochrane Collaboration. Discussion: We propose a stepwise strategy to support the development, validation, and application of evidence-based toxicology (EBT). We discuss current progresses in this field produced by the Office of Health Assessment and Translation (OHAT) of the National Toxicology Program and the Navigation Guide works. We propose that adherence to the Cochrane principles is a fundamental prerequisite for the development and implementation of EBT. Conclusion: The adoption of evidence-based principles and methods will enhance the validity, transparency, efficiency, and acceptance of toxicological evidence, with benefits in terms of reducing delays and costs for all stakeholders (researchers, consumers, regulators, and industry). © 2015, Public Health Services, US Dept of Health and Human Services. All rights reserved.


Mandrioli D.,Ramazzini Institute | Belpoggi F.,Ramazzini Institute | Perry M.J.,George Washington University
Environmental Health: A Global Access Science Source | Year: 2016

Aneuploidy, defined as structural and numerical aberrations of chromosomes, continues to draw attention as an informative effect biomarker for carcinogens and male reproductive toxicants. It has been well documented that aneuploidy is a hallmark of cancer. Aneuploidies in oocytes and spermatozoa contribute to infertility, pregnancy loss and a number of congenital abnormalities, and sperm aneuploidy is associated with testicular cancer. It is striking that several carcinogens induce aneuploidy in somatic cells, and also adversely affect the chromosome compliment of germ cells. In this paper we review 1) the contributions of aneuploidy to cancer, infertility, and developmental abnormalities; 2) techniques for assessing aneuploidy in precancerous and malignant lesions and in sperm; and 3) the utility of aneuploidy as a biomarker for integrated chemical assessments of carcinogenicity, and reproductive and developmental toxicity. © 2016 The Author(s).


Background Artificially sweetened beverage consumption has steadily increased in the last 40 years. Several reviews examining the effects of artificially sweetened beverages on weight outcomes have discrepancies in their results and conclusions. Objectives To determine whether risk of bias, results, and conclusions of reviews of effects of artificially sweetened beverage consumption on weight outcomes differ depending on review sponsorship and authors' financial conflicts of interest. Methods We performed a systematic review of reviews of the effects of artificially sweetened beverages on weight. Two assessors independently screened articles for inclusion, extracted data, and assessed risks of bias. We compared risk of bias, results and conclusions of reviews by different industry sponsors, authors' financial conflict of interest and journal sponsor. We also report the concordance between review results and conclusions. Results Artificial sweetener industry sponsored reviews were more likely to have favorable results (3/4) than non-industry sponsored reviews (1/23), RR: 17.25 (95% CI: 2.34 to 127.29), as well as favorable conclusions (4/4 vs. 15/23), RR: 1.52 (95% CI: 1.14 to 2.06). All reviews funded by competitor industries reported unfavorable conclusions (4/4). In 42% of the reviews (13/31), authors' financial conflicts of interest were not disclosed. Reviews performed by authors that had a financial conflict of interest with the food industry (disclosed in the article or not) were more likely to have favorable conclusions (18/22) than reviews performed by authors without conflicts of interest (4/9), RR: 7.36 (95% CI: 1.15 to 47.22). Risk of bias was similar and high in most of the reviews. Conclusions Review sponsorship and authors' financial conflicts of interest introduced bias affecting the outcomes of reviews of artificially sweetened beverage effects on weight that could not be explained by other sources of bias. © 2016 Mandrioli et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


PubMed | University of Amsterdam, University of Liverpool, University of New South Wales, University of Missouri - Kansas City and 9 more.
Type: | Journal: Environment international | Year: 2016

There is high demand in environmental health for adoption of a structured process that evaluates and integrates evidence while making decisions and recommendations transparent. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework holds promise to address this demand. For over a decade, GRADE has been applied successfully to areas of clinical medicine, public health, and health policy, but experience with GRADE in environmental and occupational health is just beginning. Environmental and occupational health questions focus on understanding whether an exposure is a potential health hazard or risk, assessing the exposure to understand the extent and magnitude of risk, and exploring interventions to mitigate exposure or risk. Although GRADE offers many advantages, including its flexibility and methodological rigor, there are features of the different sources of evidence used in environmental and occupational health that will require further consideration to assess the need for method refinement. An issue that requires particular attention is the evaluation and integration of evidence from human, animal, in vitro, and in silico (computer modeling) studies when determining whether an environmental factor represents a potential health hazard or risk. Assessment of the hazard of exposures can produce analyses for use in the GRADE evidence-to-decision (EtD) framework to inform risk-management decisions about removing harmful exposures or mitigating risks. The EtD framework allows for grading the strength of the recommendations based on judgments of the certainty in the evidence (also known as quality of the evidence), as well as other factors that inform recommendations such as social values and preferences, resource implications, and benefits. GRADE represents an untapped opportunity for environmental and occupational health to make evidence-based recommendations in a systematic and transparent manner. The objectives of this article are to provide an overview of GRADE, discuss GRADEs applicability to environmental health, and identify priority areas for method assessment and development.


PubMed | George Washington University and Ramazzini Institute
Type: Review | Journal: Environmental health : a global access science source | Year: 2016

Aneuploidy, defined as structural and numerical aberrations of chromosomes, continues to draw attention as an informative effect biomarker for carcinogens and male reproductive toxicants. It has been well documented that aneuploidy is a hallmark of cancer. Aneuploidies in oocytes and spermatozoa contribute to infertility, pregnancy loss and a number of congenital abnormalities, and sperm aneuploidy is associated with testicular cancer. It is striking that several carcinogens induce aneuploidy in somatic cells, and also adversely affect the chromosome compliment of germ cells. In this paper we review 1) the contributions of aneuploidy to cancer, infertility, and developmental abnormalities; 2) techniques for assessing aneuploidy in precancerous and malignant lesions and in sperm; and 3) the utility of aneuploidy as a biomarker for integrated chemical assessments of carcinogenicity, and reproductive and developmental toxicity.


PubMed | Medical University of South Carolina, c National Institute for Insurance Against Injuries at Work INAIL and Ramazzini Institute
Type: Journal Article | Journal: International journal of radiation biology | Year: 2016

Background In 2002 the International Agency for Research on Cancer classified extremely low frequency magnetic fields (ELFMF) as a possible carcinogen on the basis of epidemiological evidence. Experimental bioassays on rats and mice performed up to now on ELFMF alone or in association with known carcinogens have failed to provide conclusive confirmation. Objectives To study the carcinogenic effects of combined exposure to sinusoidal-50Hz (S-50 Hz) magnetic fields and acute radiation in Sprague-Dawley rats. Methods We studied groups of male and female Sprague-Dawley rats exposed from prenatal life until natural death to 20 or 1000T S-50 Hz MF and also to 0.1Gy radiation delivered as a single acute exposure at 6 weeks of age. Results The results of the study showed significant carcinogenic effects for the mammary gland in males and females and a significant increased incidence of malignant schwannomas of the heart as well as increased incidence of lymphomas/leukemias in males. Conclusions These results call for a re-evaluation of the safety of non-ionizing radiation.


Soffritti M.,Ramazzini Institute | Falcioni L.,Ramazzini Institute | Bua L.,Ramazzini Institute | Tibaldi E.,Ramazzini Institute | And 2 more authors.
American Journal of Industrial Medicine | Year: 2013

Background: More than 10 years have passed since the terrorist attack on the New York City World Trade Center on September 11, 2001. It is well known that long-term carcinogenic bioassays on rodents can predict the potential carcinogenic effects of chemical and physical agents for humans. Objective: A life-span carcinogenicity bioassay was conducted on Sprague-Dawley rats at the CMCRC of the Ramazzini Institute to test the potential carcinogenic effects of settled dust collected at the WTC immediately after the terrorist attack. Methods: The WTC material tested is a complex mixture of coarse particles (95%) contain pulverized cement, glass fibres, asbestos, lead, polycyclic aromatic hydrocarbons (PAHS), polychlorinated biphenyls (PCBS) and polychlorinated furans, and dioxin. The test matter was suspended in sterile saline and administered by intratracheal instillation (IT) to 8-week-old Sprague-Dawley rats (100 animals/sex), 3-4 days/week for 4 weeks. A group of 200 male and female rats served as controls. The animals were kept under observation until natural death. Results: Histopathological evaluation of the lungs (target organ) of instilled control and treated male and female rats, did not show any significant increased incidence of lung tumors. Two hemangiomas (one with endothelial atypia) and one hemangiosarcoma were found in the lungs of treated males. Moreover a modest increased incidence of terminal bronchiolar hyperplasia (TBH) and squamous metaplasia occurred in the lung of treated males and females compared to the controls. Conclusion: Hemangioma and hemangiosarcoma are extremely rare tumors in the lung of our colony and we believe they are caused by WTC dust. © 2012 Wiley Periodicals, Inc.


Soffritti M.,Ramazzini Institute | Belpoggi F.,Ramazzini Institute | Manservigi M.,Ramazzini Institute | Tibaldi E.,Ramazzini Institute | And 3 more authors.
American Journal of Industrial Medicine | Year: 2010

Aspartame (APM) is a well-known intense artificial sweetener used in more than 6,000 products. Among the major users of aspartame are children and women of childbearing age. In previous lifespan experiments conducted on Sprague-Dawley rats we have shown that APM is a carcinogenic agent in multiple sites and that its effects are increased when exposure starts from prenatal life.Objective: The aim of this study is to evaluate the potential of APM to induce carcinogenic effects in mice.Methods: Six groups of 62-122 male and female Swiss mice were treated with APM in feed at doses of 32,000, 16,000, 8,000, 2,000, or 0 ppm from prenatal life (12 days of gestation) until death. At death each animal underwent complete necropsy and all tissues and organs of all animals in the experiment were microscopically examined.Results: APM in our experimental conditions induces in males a significant dose-related increased incidence of hepatocellular carcinomas (P < 0.01), and a significant increase at the dose levels of 32,000 ppm (P < 0.01) and 16,000 ppm (P < 0.05). Moreover, the results show a significant dose-related increased incidence of alveolar/bronchiolar carcinomas in males (P < 0.05), and a significant increase at 32,000 ppm (P < 0.05).Conclusions: The results of the present study confirm that APM is a carcinogenic agent in multiple sites in rodents, and that this effect is induced in two species, rats (males and females) and mice (males). No carcinogenic effects were observed in female mice. © 2010 Wiley-Liss, Inc.


Soffritti M.,Ramazzini Institute | Padovani M.,Ramazzini Institute | Tibaldi E.,Ramazzini Institute | Falcioni L.,Ramazzini Institute | And 2 more authors.
American Journal of Industrial Medicine | Year: 2014

Aspartame (APM) is an artificial sweetener used since the 1980s, now present in >6,000 products, including over 500 pharmaceuticals. Since its discovery in 1965, and its first approval by the US Food and Drugs Administration (FDA) in 1981, the safety of APM, and in particular its carcinogenicity potential, has been controversial. The present commentary reviews the adequacy of the design and conduct of carcinogenicity bioassays on rodents submitted by G.D. Searle, in the 1970s, to the FDA for market approval. We also review how experimental and epidemiological data on the carcinogenic risks of APM, that became available in 2005 motivated the European Commission (EC) to call the European Food and Safety Authority (EFSA) for urgent re-examination of the available scientific documentation (including the Searle studies). The EC has further requested that, if the results of the evaluation should suggest carcinogenicity, major changes must be made to the current APM specific regulations. Taken together, the studies performed by G.D. Searle in the 1970s and other chronic bioassays do not provide adequate scientific support for APM safety. In contrast, recent results of life-span carcinogenicity bioassays on rats and mice published in peer-reviewed journals, and a prospective epidemiological study, provide consistent evidence of APM's carcinogenic potential. On the basis of the evidence of the potential carcinogenic effects of APM herein reported, a re-evaluation of the current position of international regulatory agencies must be considered an urgent matter of public health. Am. J. Ind. Med. 57:383-397, 2014. © 2014 Wiley Periodicals, Inc.


PubMed | Ramazzini Institute
Type: Journal Article | Journal: International journal of occupational and environmental health | Year: 2016

Sucralose is an organochlorine artificial sweetener approximately 600 times sweeter than sucrose and used in over 4,500 products. Long-term carcinogenicity bioassays on rats and mice conducted on behalf of the manufacturer have failed to show the evidence of carcinogenic effects.The aim of this study was to evaluate the carcinogenic effect of sucralose in mice, using a sensitive experimental design.Five groups of male (total n=457) and five groups female (total n=396) Swiss mice were treated from 12days of gestation through the lifespan with sucralose in their feed at concentrations of 0, 500, 2,000, 8,000, and 16,000ppm.We found a significant dose-related increased incidence of males bearing malignant tumors (p<0.05) and a significant dose-related increased incidence (p<0.01) of hematopoietic neoplasias in males, in particular at the dose levels of 2,000ppm (p<0.01) and 16,000ppm (p<0.01).These findings do not support previous data that sucralose is biologically inert. More studies are necessary to show the safety of sucralose, including new and more adequate carcinogenic bioassay on rats. Considering that millions of people are likely exposed, follow-up studies are urgent.

Loading Ramazzini Institute collaborators
Loading Ramazzini Institute collaborators