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At Heineken UK, we have applied 5S principles to the legislation and guidance set out by the Health and Safety Executive (HSE) to develop a set of procedures and training materials to simplify the entire COSHH process and ensure compliance with HSE regulations. Most notably, we have complete visibility of all COSHH assessments and safety data sheets through “COSHH Boards” and “COSHH Tubes” on each of our production lines for ease of access to critical information in an emergency. We have found these procedures and the application of 5S to drastically save time, improve COSHH assessment quality and chemical control across an entire site. The engagement and awareness of our colleagues on chemical safety has dramatically increased on our journey to a zero accident workplace.

Read-across has become a primary approach to fill data gaps for chemical safety assessments. Chemical similarity based on structure, reactivity, and physic-chemical property information is a traditional approach applied for read-across toxicity studies. However, toxicity mechanisms are usually complicated in a biological system, so only using chemical similarity to perform the read-across for new compounds was not satisfactory for most toxicity endpoints, especially when the chemically similar compounds show dissimilar toxicities. This study aims to develop an enhanced read-across method for chemical toxicity predictions. To this end, we used two large toxicity datasets for read-across purposes. One consists of 3,979 compounds with Ames mutagenicity data, and the other contains 7,332 compounds with rat acute oral toxicity data. First, biological data for all compounds in these two datasets were obtained by querying thousands of PubChem bioassays. The PubChem bioassays with at least five compounds from either of these two datasets showing active responses were selected to generate comprehensive bioprofiles. The read-across studies were performed by using chemical similarity search only and also by using a hybrid similarity search based on both chemical descriptors and bioprofiles. Compared to traditional read-across based on chemical similarity, the hybrid read-across approach showed improved accuracy of predictions for both Ames mutagenicity and acute oral toxicity. Furthermore, we could illustrate potential toxicity mechanisms by analyzing the bioprofiles used for this hybrid read-across study. The results of this study indicate that the new hybrid read-across approach could be an applicable computational tool for chemical toxicity predictions. In this way, the bottleneck of traditional read-across studies can be overcome by introducing public biological data into the traditional process. The incorporation of bioprofiles generated from the additional biological data for compounds can partially solve the “activity cliff” issue and reveal their potential toxicity mechanisms. This study leads to a promising direction to utilize data-driven approaches for computational toxicology studies in the big data era.

The Read-Across Assessment Framework (RAAF) was developed by the European Chemicals Agency (ECHA) as an internal tool providing a framework for a consistent, structured and transparent assessment of grouping of chemicals and read-across. Following a RAAF-based evaluation, also developers and users of read-across predictions outside ECHA can judge whether their read-across rationale is sufficiently robust from a regulatory perspective. The aim of this paper is to describe the implementation of RAAF functionalities in the OECD QSAR Toolbox report. These can be activated in the prediction report after performing a readacross prediction. Once the user manually selects the appropriate scenario, the RAAF assessment elements appear and are automatically aligned with the suitable category elements of the Toolbox report. Subsequently, these are evaluated as part of the category consistency assessment functionality. The implementation of the RAAF functionality is illustrated in practice with two examples.

Humans are continuously exposed to complex chemical mixtures from foods and the environment. Due to our inadequate understanding of mixture effects, tools to assess the combined risk of mixed chemical exposures have been difficult to develop. In recent years, regulatory authorities across the world have made considerable progress towards developing pragmatic frameworks to deal with combined exposure to multiple chemicals for risk assessment purposes. These approaches require a high level of information about chemical exposures and toxicities, information that often is lacking. We see this data gap as delaying urgently needed improvements in chemical safety. Herein, we present a pragmatic step-by-step procedure for mixture risk assessment and propose tools for grouping of chemicals. Until we have a better understanding of adverse outcome pathways, we suggest that grouping of chemicals for mixture risk assessment be based on integrated in vivo and in vitro data, read-across as well as computational methods such as QSAR models or integrative systems biology. These latter methods can be used to predict inherent hazards or modes/mechanisms of action and to group the chemicals in cases where no experimental data exist.

Acceptance of new approach methodologies (NAMs) for use in characterizing chemical hazard and risk requires informed expectations regarding the minimum precision and maximum accuracy of their results. Uncertainty in NAMs derived from variability in the traditional reference data used to train or validate performance of the NAM, and uncertainty in the modeling procedures themselves, limits NAM performance. Herein, we review current approaches to characterizing uncertainty in NAMs. We discuss variability in in vivo data used as a reference for NAM development and validation; the quantitative uncertainty in concentration–response modeling for high-throughput in vitro bioactivity screening; the uncertainties associated with in vitro to in vivo extrapolation using toxicokinetic information; and the quantitative uncertainty in the experimental inputs and modeled outputs from quantitative structure activity relationship models for prediction of point of departure doses. Communication of the amount of uncertainty, both in the input and output for NAMs, often involves a confidence or prediction interval around a given potency estimate, derived from an understanding of the variability in the data modeled. Tuning expectations of NAM performance to an understanding of the reproducibility and variability, both of traditional approaches and NAM approaches, provides a path for the adoption of NAMs as alternatives in screening chemicals for risk.

One of the first pieces of legislation addressing the UK's departure from the EU/Euratom to complete its passage through Parliament is the Nuclear Safeguards Act 2018, which will enable the government to establish a domestic nuclear safeguards regime. This was driven by the need to prevent vulnerability to a vital energy system and indicates the short to medium term approach the UK has to its policymaking post-Brexit: dealing with issues immediately impacted, such as ensuring the continued supply of nuclear fuel. The contribution of this paper is the examination of two particular areas under the responsibility of Euratom – nuclear safeguards and radiation protection – that are presented to indicate the wider impact Brexit has in other areas currently the responsibility of the EU, for example, chemical safety. It shows that the UK has significant gaps in responsibility currently undertaken by Euratom (or other EU institutions) that need to be filled by UK bodies. Which bodies will assume these responsibilities and what resources will be available remain open questions. This case study highlights the need for systematic prioritisation by the UK government when filling the void of EU/Euratom institutions.

Spurred by the vision articulated in the National Academy of Sciences report Toxicity Testing in the 21st Century (2007) and the availability of advanced methods for biological profiling of chemicals, large volumes of data describing in vitro effects have been generated over the last 10 years for thousands of chemicals. Additional important drivers in transforming toxicity testing and safety evaluation include the National Academy of Sciences report Using 21st Century Science to Improve Risk-Related Evaluations (2017) and the passage of the Frank R. Lautenberg Chemical Safety for the 21st Century Act, which amended the Toxic Substances Control Act to require development and implementation of tiered approaches for risk-based safety evaluations and for the Environmental Protection Agency to develop, evaluate, and use New Approach Methodologies. Considerable efforts are now being devoted to interpreting results, determining how these relate to potential health effects, and integrating bioactivity with predicted or measured human exposures for product safety evaluations. This article presents a number of my perspectives on the transformation that New Approach Methodologies are catalyzing in regulatory safety evaluations and product stewardship of commodity and consumer product chemicals.

Cold plasma is an ideal antimicrobial agent with a gamut of reactive chemical species, that could be obtained from electrical discharges in atmospheric gases. The reactive species are effective against a range of microorganisms, including bacteria, fungi, spores and viruses, as well as pesticides and mycotoxins. Generation of cold plasma inside sealed packages allows to localise and extend the action time of reactive species on microorganisms, while preventing any post-process contamination. In this review, we present an examination of the design aspects of the in-package plasma systems, the packaging requirements, and discuss their efficacy with respect to microbiological and chemical safety of foods.

Food packaging facilitates storage, handling, transport, and preservation of food and is essential for preventing food waste. Besides these beneficial properties, food packaging causes rising concern for the environment due to its high production volume, often short usage time, and problems related to waste management and littering. Reduction, reuse, and recycling, but also redesign support the aims of the circular economy. These tools also have the potential to decrease the environmental impact of food packaging. In this article, we focus on chemical safety aspects of recycled food packaging, as recycling is currently seen as an important measure to manage packaging waste. However, recycling may increase the levels of potentially hazardous chemicals in the packaging and -after migration- in the food. Since exposure to certain chemicals migrating from food packaging has been associated with chronic diseases, it is of high importance to assess the safety of recycled packaging. Therefore, we describe recycling processes of commonly used food packaging materials, including plastics, paper and board, aluminum, steel, and multimaterial multilayers (e.g., beverage cartons). Further, we give an overview of typical migrants from all types of recycled food packaging materials, and summarize approaches to reduce chemical contamination. We discuss the role of food packaging in the circular economy, where recycling is only one of many complementary tools for providing environmentally-friendly and safe food packaging.

Food safety is a growing concern for consumers, public authorities and food-chain stakeholders. Ensuring food safety is becoming increasingly important with regard to changing food habits and the globalization of food supply. This makes assessing chemical food safety a crucial issue, as food can be contaminated by various toxicants throughout the food chain. At farm level, raw materials can be contaminated by agrochemicals, including pesticides and veterinary drugs, as well as by environmental micropollutants such as POPs or heavy metals. Further chemical hazards associated to the occurrence of toxicants or to cross-contaminations can also arise during transport, processing or storage. This article presents and discusses recent advances in chemical food safety. Taking meat as a model, it gives an overview of promising novel approaches to better control the occurrence of chemical toxicants along the food chain, improve their risk assessment, and reduce their impact on human health by proposing novel mitigation strategies. Industrial relevance As meat may be contaminated by various chemical toxicants, its chemical safety is a growing concern for public authorities, industrials and consumers. This paper gives the different toxic contaminants potentially found in meat products and the possible strategies for their detection, mitigation and health impact assessment. This knowledge would permit industrials to develop new distinctive labels for safe food as well as to produce new ready-to-eat foods free of process-induced toxicants or original recipes to add to dishes to reduce the health impact of these toxicants. Knowing the toxicant bioaccessibility would also permit industrials to target precise food product composition depending on the raw materials and the consumers' class. It finally proposes emerging analytical approaches to enable a more systematic control of meat chain. All the strategies developed herein on meat products could be transposable to other food chains of industrial interest and with products potentially contaminated from farm to fork.

Pharmaceutical drug products (DP) can contain foreign impurities due to contact with manufacturing, storage, distribution and administration systems. These foreign impurities (leachables) are leached from these systems by the drug product and can be linked to extractables measured in the systems during laboratory investigations. Assessing the impact of leachables on the suitability of the DP requires that it be screened to discover, identify and quantify leachables. Given the large number and great chemical diversity of potential leachables, an analytical strategy involving multiple, orthogonal analytical methods is necessary to generate a complete leachables profile. Once the profile has been delineated, the effect of leachables on the DP's suitability can be established. The potential adverse effect of leachables on patient safety can be established via chemical safety risk assessment, which involves comparing a DP user's (patient) exposure to individual leachables with exposure thresholds which are toxicologically established for the individual leachables.

This commentary offers some perspectives on the future of in silico chemical safety assessment, grouped into four main themes: science, technology, regulation, and culture. The commentary is based on a talk given by Dr Andrew Worth at a Symposium entitled “Navigating In Silico Chemical Safety” held at the Friedrich-Alexander-University (FAU) in Erlangen, Germany on 11 October 2018.

In vitro chemical safety testing methods offer the potential for efficient and economical tools to provide relevant assessments of human health risk. To realize this potential, methods are needed to relate in vitro effects to in vivo responses, i.e., in vitro to in vivo extrapolation (IVIVE). Currently available IVIVE approaches need to be refined before they can be utilized for regulatory decision-making. To explore the capabilities and limitations of IVIVE within this context, the U.S. Environmental Protection Agency Office of Research and Development and the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods co-organized a workshop and webinar series. Here, we integrate content from the webinars and workshop to discuss activities and resources that would promote inclusion of IVIVE in regulatory decision-making. We discuss properties of models that successfully generate predictions of in vivo doses from effective in vitro concentration, including the experimental systems that provide input parameters for these models, areas of success, and areas for improvement to reduce model uncertainty. Finally, we provide case studies on the uses of IVIVE in safety assessments, which highlight the respective differences, information requirements, and outcomes across various approaches when applied for decision-making.

Reproductive toxicity chemical safety assessment involves extensive use of vertebrate animals for regulatory testing purposes. Although alternative methods such as the zebrafish embryo teratogenicity assay (identified in the present manuscript by the acronym ZETA) are promising for replacing tests with mammals, challenges to regulatory application involve lack of standardization and incomplete validation. To identify key protocol aspects and ultimately support improving this situation, a comprehensive review of the literature on the level of harmonization/standardization and validation status of the ZETA has been conducted. The gaps and needed advances of the available ZETA protocols were evaluated and discussed with respect to its applicability as an alternative approach for teratogenicity assessment. Based on the review outcomes, a set of minimum reporting standards for the experimental protocol is proposed. Together with other initiatives towards implementation of alternative approaches at the screening and regulatory levels, the application of minimum reporting requirements is anticipated to support future method standardization and validation, as well as identifying potential improvement aspects. Present findings are expected to ultimately support advancing the ongoing validation initiatives towards the regulatory acceptance of the ZETA.

Background Chemical hazard communication (e.g., label) is intended to alert users of the potential hazards of chemicals. Apart from the fact that hazard information needs to be understood, it is also important that it is recalled. Recall of hazard communication is critical when the written form of the information is not available at the time it is required. Methods A cross-sectional study investigating associations between the recall of chemical safety information on labels and safety data sheets among 402 participants including 315 workers (industry, transport and agriculture sectors) and 87 consumers in two provinces of South Africa was conducted. The recall of label information by participants was tested using two modules from a Hazard Communication Comprehensibility Testing (CT) Tool developed by the Centre for Environmental and Occupational Health Research at the University of Cape Town for the UN Institute for Training and Research (UNITAR). Results Respondents were predominantly male (67.7%), the median age was 37 years (IQR: 30–46 years) and less than half of the participants completed high school (47.5%). The skull and crossbones symbol was the label element most recalled, both freely without prompting (79.6%) and recognition after prompting (94.8%). Whereas, the first aid and treatment measures were the least frequently freely recalled (least frequent item 6.0%; most frequent item 29.9%). Multivariate analysis identified the following positive associations with the recall of all the label elements listing the strongest association: call appropriate services and industrial vs. consumer sector (OR = 2.4; 95% CI: 1.2; 4.6); call appropriate services and transport vs. consumer sector (OR = 4.4; 95% CI: 1.2; 16.0); flammable symbol and male vs. female gender (OR = 2.3; 95% CI: 1.0; 5.3); flammable symbol and home language English vs. African languages (OR = 6.6; 95% CI: 2.1; 21.2); any hazard statement and home language Afrikaans vs. African languages (OR = 14.0; 95% CI: 3.6; 54.2), any first aid statement and further education vs. none (OR = 3.3; 95% CI: 1.3; 8.0), correct chemical name and industry blue collar workers vs. non-industry blue collar workers (OR = 2.6; 95% CI: 1.1; 6.1), correct chemical name and non-industry white collar occupations vs. non-industry blue collar workers (OR = 2.7; 95% CI: 1.0; 7.1). Conclusion The study found a number of potential positive associations that influence recall of label elements of which some (e.g., sector, gender, occupation) suggest further research. Relevant policies in South Africa should ensure that the safety information on chemical labels is clearly visible to read and understandable which aids recall and the reduction in harmful chemical exposures.

The oil and gas industry has been beset with several catastrophic accidents, most of which have been attributed to organisational and operational human factor errors. The current HFACS developed for the aviation industry, cannot be used to simultaneously analyse regulatory deficiencies and emerging violation issues, such as sabotage in the oil and gas industry. This paper presents an attempt to improve the existing HFACS investigation tool and proposes a novel HFACS named the Human Factors Analysis and Classification System for the Oil and Gas Industry (HFACS-OGI). Results found the HFACS-OGI system to be suitable for categorising accidents, following the analysis of 11 accident reports from the US Chemical Safety Board (US CSB). The HFACS-OGI system moreover revealed some significant relationships between the different categories. Furthermore, the results indicated that failures in national and international industry regulatory standards would automatically create the preconditions for accidents to occur.

On June 1st, 2007 the European regulation on Registration, Evaluation and Restriction of Chemical substances (REACH) came into force. Aim of the regulation is safe use of chemicals for humans and for the environment. The core element of REACH is chemical safety assessment of chemicals and communication of health and safety hazards and risk management measures throughout the supply chain. Extended Safety Data Sheets (Ext-SDS) are the primary carriers of health and safety information. The aim of our project was to find out whether the actual exposure to methyl methacrylate (MMA) during the application of polymethylmethacrylate (PMMA) in floor coatings as assessed in the chemical safety assessment, reflect the exposure situations as observed in the Dutch building practice. Use of PMMA flooring and typical exposure situations during application were discussed with twelve representatives of floor laying companies. Representative situations for exposure measurements were designated on the basis of this inventory. Exposure to MMA was measured in the breathing zone of the workers at four construction sites, 14 full shift samples and 14 task based samples were taken by personal air sampling. The task-based samples were compared with estimates from the Targeted Risk Assessment Tool (v3.1) of the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC-TRA) as supplied in the safety assessment from the manufacturer. For task-based measurements, in 12 out of 14 (86%) air samples measured exposure was higher than estimated exposure. Recalculation with a lower ventilation rate (50% instead of 80%) together with a higher temperature during mixing (40°C instead of 20°C) in comparison with the CSR, reduced the number of underestimated exposures to 10 (71%) samples. Estimation with the EMKG-EXPO-Tool resulted in unsafe exposure situations for all scenarios, which is in accordance with the measurement outcomes. In indoor situations, 5 out of 8 full shift exposures (62%) to MMA were higher than the Dutch occupational exposure limit of 205mg/m3 (8h TWA), which equals the DNEL. For semi-enclosed situations this was 1 out of 6 (17%). Exposures varied from 31 to 367mg/m3. The results emphasize that ECETOC-TRA exposure estimates in poorly controlled situations need better underpinning.

Storage of fertilizer grade ammonium nitrate (FGAN) is common worldwide. The material is stable when stored at ambient temperatures. However, ammonium nitrate is explosive when exposed to higher temperatures and/or a shock wave source. The presence of even 0.2% carbon adds to the blast potential. This paper summarizes the key finding of an ammonium nitrate explosion that occurred at a FGAN storage facility on 17 April 2013 in West, Texas, USA. 15 people were killed including12 emergency responders who were fighting a fire that occurred on the property before the explosion. Over 260 were injured. The key lessons learned are reviewed and recommendations are offered below.

For the purposes of chemical safety assessment, the value of using non-animal (in silico and in vitro) approaches and generating mechanistic information on toxic effects is being increasingly recognised. For sectors where in vivo toxicity tests continue to be a regulatory requirement, there has been a parallel focus on how to refine studies (i.e. reduce suffering and improve animal welfare) and increase the value that in vivo data adds to the safety assessment process, as well as where to reduce animal numbers where possible. A key element necessary to ensure the transition towards successfully utilising both non-animal and refined safety testing is the better understanding of chemical exposure. This includes approaches such as measuring chemical concentrations within cell-based assays and during in vivo studies, understanding how predicted human exposures relate to levels tested, and using existing information on human exposures to aid in toxicity study design. Such approaches promise to increase the human relevance of safety assessment, and shift the focus from hazard-driven to risk-driven strategies similar to those used in the pharmaceutical sectors. Human exposure-based safety assessment offers scientific and 3Rs benefits across all sectors marketing chemical or medicinal products. The UK's National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) convened an expert working group of scientists across the agrochemical, industrial chemical and pharmaceutical industries plus a contract research organisation (CRO) to discuss the current status of the utilisation of exposure-driven approaches, and the challenges and potential next steps for wider uptake and acceptance. This paper summarises these discussions, highlights the challenges - particularly those identified by industry - and proposes initial steps for moving the field forward.

Assessment of potential adverse effects on the immune system is an important component of the chemical safety evaluation process. As alternative testing methods are rapidly evolving, there is a progressing interest to determine their practical implementation for reducing or replacing existing in vivo studies without compromising chemical safety. There has been considerable progress in the development of alternative testing methods for dermal sensitization, however, the methods for evaluating respiratory sensitization and immunosuppression are still at various stages of development and validation. This review highlights the current status of alternative testing methods and practical considerations for implementation from a chemical industry perspective.

The presentation will discuss the difference between EU and US standards for the determination of explosion (flammability) limits and limiting oxygen concentration. Small differences observed in measured values can be traced back to the different test apparatuses and criteria. The discrepancies can be much greater in the case of limiting oxygen concentration because of the high amount of inert gases and the corresponding low laminar burning velocities. The paper describes some examples and the influence of the chosen criteria on the results. The European and US standards use the criteria of flame propagation in open test vessels and of pressure rise in closed ones. The examples discussed show that flame propagation is still possible at very small pressure rise values, as observed much below the pressure rise criterion of usual standards. However, flame propagation in a process plant can cause an accident or explosion and must be avoided. Therefore, the flame propagation criterion is recommended to be used in chemical safety engineering. The European safety database CHEMSAFE contains expert-evaluated safety data for cases where the determination method and criteria are known. Flammability characteristics based on the pressure rise criterion may suffice in certain cases, e.g. for explosion protection in closed vessels without any connecting pipes.

While biomarker discovery is receiving increased attention in both drug and chemical safety assessment, a critical step is transitioning a biomarker from an experimental observation to a useful assay is that of analytical validation. This is particularly relevant as one moves from biomarker discovery using an omics platform to exploratory use as implemented in a more focused platform. Large scale discovery platforms for transcriptomics, such as microarrays, have unique analytical considerations, different from that of more focused platforms, such as qRT-PCR. Likewise, mass spectrometry based screens of the proteome have different analytical challenges as compared to focused ELISA assays. Metabolomics experiments also require attention to analytical validation, with different considerations for quantitative or semi-quantitative assays. And while guidelines for analytical validation are still evolving, general principles certainly apply, with a solid body of literature that should be consulted by the biomarker scientist before deeming an assay as worthy of more widespread use.

The evolved World Health Organization/International Programme on Chemical Safety mode of action (MOA) framework provides a structure for evaluating evidence in pathways of causally linked key events (KE) leading to adverse health effects. Although employed globally, variability in use of the MOA framework has led to different interpretations of the sufficiency of evidence in support of hypothesized MOAs. A proof of concept extension of the MOA framework is proposed for scoring confidence in the supporting data to improve scientific justification for MOA use in characterizing hazards and selecting dose-response extrapolation methods for specific chemicals. This involves selecting hypothesized MOAs, and then, for each MOA, scoring the weight of evidence (WOE) in support of causality for each KE using evolved Bradford Hill causal considerations (biological plausibility, essentiality, dose-response concordance, consistency, and analogy). This early proof of concept method is demonstrated by comparing two potential MOAs (mutagenicity and peroxisome proliferator activated receptor-alpha) for clofibrate, a rodent liver carcinogen. Quantitative confidence scoring of hypothesized MOAs is shown to be useful in characterizing the likely operative MOA. To guide method refinement and future confidence scoring for a spectrum of MOAs, areas warranting further focus and lessons learned, including the need to incorporate a narrative discussion of the weights used in the evaluation and an overall evaluation of the plausibility of the outcome, are presented.

Process safety incidents can result in injuries, fatalities, environmental impacts, facility damage, downtime & lost production, as well as impacts on a company's and industry's reputation. This study is focused on an analysis of the most commonly reported contributing factors to process safety incidents in the US chemical manufacturing industry. The database for the study contained 79 incidents from 2010 to 2019, partly investigated by the Chemical Safety Board (CSB). To be included in the study, the CSB archive of incident investigations were parsed to include only incidents which occurred at a company classified as 325 in the North American Industry Classification System (NAICS), assigned to businesses that participate in chemical manufacturing. For each incident, all of the identified contributing factors were catalogued in the database. From this list of identified contributing factors, it was possible to name the ‘top three’ contributing factors. The top three contributing factors cited for the chemical manufacturing industry were found to be: design; preventive maintenance; and safeguards, controls & layers of protection. The relationship between these top contributing factors and the most common OSHA citations was investigated as well. The investigation and citation history for NAICS 325 companies in the Occupational Safety & Health Administration (OSHA) citations database was then analysed to assess whether there was any overlap between the top reported contributing factors to process safety events and the top OSHA citations recorded for the industry. A database consisting of the inspection and citation history for the chemical manufacturing industry identified by NAICS code 325 was assembled for inspections occurring between 2010 and 2020 (August). The analysis of the citation history for the chemical manufacturing industry specifically, identified that the list of the top contributing factors to process safety incidents overlapped with the most common OSHA violations. This finding is relevant to industry stakeholders who are considering how to strategically invest resources for achieving maximum benefit – reducing process safety risk and simultaneously improving OSHA citation history.

La contaminación del planeta alcanza también al ecosistema de la lactancia, uno de los más íntimos e inviolables que nos liga como especie animal al resto de los mamíferos. Las madres lactantes pueden estar preocupadas sobre si la calidad de su leche será la adecuada para su bebé y si los contaminantes medioambientales, a través del trabajo, la dieta y el envasado, pueden afectar a su hijo desfavorablemente. La leche materna es fuente de exposición a contaminantes medioambientales, y al mismo tiempo contrabalancea muchos de los efectos de estas exposiciones. Un enfoque basado en los principios de realidad y precaución de la salud medioambiental para evitar, reducir o eliminar la producción y el uso de sustancias químicas nocivas durante el embarazo y la lactancia aseguran a la descendencia una mejor salud humana y del planeta, The pollution of the planet also reaches the breastfeeding ecosystem, one of the most intimate and inviolable that links us as an animal species to the rest of mammals. Nursing mothers may be concerned about whether the quality of their milk will be adequate for their baby and whether environmental pollutants through work, diet, and storing may adversely affect their child. Breast milk is a source of exposure to environmental pollutants, and at the same time it counteracts much of the effects of these exposures. An approach based on the principles of reality and precaution of environmental health to avoid, reduce or eliminate the production and use of harmful chemicals during pregnancy and lactation would improve the human and planetary health for the offspring

Phenotypic assays using in vitro cell cultures to forecast compound effects in people are transforming pharmaceutical research and contribute to alternative methods for chemical safety testing. How these assays are validated for human disease relevance is a critical factor for developing more predictive assays. Chemical biology, using drugs as well as target-selective chemical probes, is a direct and efficient approach for establishing disease relevance. Chemical probes can connect information across assays and associate targets to clinical effects. When applied at scale, phenotypic chemical biology advances our understanding of drug and toxicity mechanisms enabling construction of disease outcome pathways. To improve the physiological relevance of phenotypic assays, standardized testing of a curated set of phenotypic pathway probes can provide a higher level of validation for phenotypic assay best practices.

Combustible dust explosions are among the most serious criticalities affecting a broad number of industries around the world. According to a Chemical Safety and Hazard Investigation Board report, more than 50 accidents have occurred only in the U.S. between 2008 and 2012; this datum shows that such a problem requires a relevant attention from both researchers and authorities. The aim of this review is to provide an overview of the currently available techniques able to estimate the severity of a combustible dust explosion. Moreover, the main criticalities arising from these methodologies are discussed, also providing some suggestions for future works.

Hundreds of millions of people around the world are exposed to elevated concentrations of inorganic and organic arsenic compounds, increasing the risk of a wide range of health effects. Studies of the environmental fate and human health effects of arsenic require authentic arsenic compounds. We summarize here the synthesis and characterization of more than a dozen methylated and thiolated arsenic compounds that are not commercially available. We discuss the methods of synthesis for the following 14 trivalent (III) and pentavalent (V) arsenic compounds: monomethylarsonous acid (MMAIII), dicysteinylmethyldithioarsenite (MMAIII(Cys)2), monomethylarsonic acid (MMAV), monomethylmonothioarsonic acid (MMMTAV) or monothio-MMAV, monomethyldithioarsonic acid (MMDTAV) or dithio-MMAV, monomethyltrithioarsonate (MMTTAV) or trithio-MMAV, dimethylarsinous acid (DMAIII), dimethylarsino-glutathione (DMAIII(SG)), dimethylarsinic acid (DMAV), dimethylmonothioarsinic acid (DMMTAV) or monothio-DMAV, dimethyldithioarsinic acid (DMDTAV) or dithio-DMAV, trimethylarsine oxide (TMAOV), arsenobetaine (AsB), and an arsenicin-A model compound. We have reviewed and compared the available methods, synthesized the arsenic compounds in our laboratories, and provided characterization information. On the basis of reaction yield, ease of synthesis and purification of product, safety considerations, and our experience, we recommend a method for the synthesis of each of these arsenic compounds.

Many incidents have helped to define and develop process safety. Each has provided valuable learning opportunities. However, it is even more important to identify insights that can be obtained from an analysis of a large set of incidents that represents those that typically occur. This larger picture illuminates trends and commonalities and provides learning opportunities that are even more important than the causes of any one individual incident. The Chemical Safety Board has published the results of over 60 investigations of process safety incidents. These data have been analyzed to identify commonalities and trends so that measures to help protect against future incidents can be developed. Recommendations are made to address key issues identified.

On December 7, 2009, a 50-foot-tall high-pressure vessel ruptured in the Nihon Dempa Kogyo Crystal, Inc. facility in Belvidere, Illinois. Several projectiles rapidly traveled outward from the facility, killing a truck driver 650 feet away and injuring an employee in another building 435 feet away. This paper summarizes the lessons learned from this incident both on causal and consequential aspects. Stress corrosion cracking was identified as the failure mechanism by the U.S. Chemical Safety and Hazard Investigation Board. After analyzing the operating conditions and the aftermath, this incident has been identified as a Boiling Liquid Expanding Vapor Explosion (BLEVE) under a supercritical pressure. A consequence analysis of the incident is performed where overpressure and fragment distance are calculated, together with safety distance estimation. Additionally, other safety-related problems, such as safety culture, management inside the corporation, and communication between this facility and the government are discussed.

A group of triazole compounds was selected to investigate the confidence that may be associated with read-across of a complex data gap: repeated dose toxicity. The read-across was evaluated using Assessment Elements (AEs) from the European Chemicals Agency's (ECHA's) Read-Across Assessment Framework (RAAF), alongside appraisal of associated uncertainties. Following an initial read-across based on chemical structure and properties, uncertainties were reduced by the integration of data streams such as those from New Approach Methodologies (NAM) and other existing data. In addition, addressing the findings of the ECHA RAAF framework, complemented with specific questions concerning uncertainties, increased the confidence that can be placed in read-across. Although a data rich group of compounds with a strong mechanistic basis was analysed, it was clearly demonstrated that NAM data available from publicly available resources could be applied to support read-across. It is acknowledged that most read-across studies will not be so data rich or mechanistically robust, therefore some targeted experimentation may be required to fill the data gaps. In this sense, NAMs should constitute new experimental tests performed with the specific goal of reducing the uncertainties and demonstrating the read-across hypothesis.

Understanding the commonalities among previous chemical process incidents can help mitigate recurring incidents in the chemical process industry and will be useful background knowledge for designers intending to foster inherent safety. The U.S. Chemical Safety and Hazard Investigation Board (CSB) reports provide detailed and vital incident information that can be used to identify possible commonalities. This study aims to develop a systematic approach for extracting data from the CSB reports with the objective of establishing these commonalities. Data were extracted based on three categories: attributed incident causes, scenarios, and consequences. Seventeen causal factors were classified as chemical indicators or process indicators. Twelve chemical indicators are associated with the hazards of the chemicals involved in the incidents, whereas five process indicators account for the hazards presented by process conditions at the time of the incident. Seven scenario factors represent incident sequences, equipment types, operating modes, process units, domino effects, detonation likelihood for explosion incidents, and population densities. Finally, three consequence factors were selected based on types of chemical incidents, casualties, population densities, and economic losses. Data from 87 CSB reports covering 94 incidents were extracted and analyzed according to the proposed approach. Based on these findings, the study proposes guidelines for future collection of information to provide valuable resources for prediction and risk reduction of future incidents.

Physiologically-based pharmacokinetic (PBPK) modeling analysis does not stand on its own for regulatory purposes but is a robust tool to support drug/chemical safety assessment. While the development of PBPK models have grown steadily since their emergence, only a handful of models have been accepted to support regulatory purposes due to obstacles such as the lack of a standardized template for reporting PBPK analysis. Here, we expand the existing guidances designed for pharmaceutical applications by recommending additional elements that are relevant to environmental chemicals. This harmonized reporting template can be adopted and customized by public health agencies receiving PBPK model submission, and it can also serve as general guidance for submitting PBPK-related studies for publication in journals or other modeling sharing purposes. The current effort represents one of several ongoing collaborations among the PBPK modeling and risk assessment communities to promote, when appropriate, incorporating PBPK modeling to characterize the influence of pharmacokinetics on safety decisions made by regulatory agencies.

Recently, new products with the name of balsamic vinegar (BV) have emerged worldwide and are rapidly gaining popularity along with the well-known Italian BVs. For the first time, the major physicochemical and sensorial characteristics of BVs produced in Greece were analyzed using recommended protocols, high throughput techniques (nuclear magnetic resonance (NMR), HPLC) and sensory descriptive analysis carried out by trained panelists. Data are discussed in comparison to those for Italian balsamic vinegars of Modena (BVMs) (Protected Geographical Indication, PGI). Greek BVs, although in line with existing official requirements, exhibited great variability in the content of individual sugars, organic acids and titratable acidity, which were reflected in both quality parameters and sensorial scores. Their heterogeneous sensorial profile was mainly characterized by high scores in Pungency , Acidity and low ones in Sweetness . From the chemical safety point of view, 5-hydroxymethyl-furfural (HMF) content was found to vary significantly, and future regulatory revision should consider this parameter. Our findings can assist the efforts of manufacturers of new BVs beyond minimum regulatory requirements.

Category formation, grouping and read across methods are broadly applicable in toxicological assessments and may be used to fill data gaps for chemical safety assessment and regulatory decisions. In order to facilitate a transparent and systematic approach to aid regulatory acceptance, a strategy to evaluate chemical category membership, to support the use of read-across predictions that may be used to fill data gaps for regulatory decisions is proposed. There are two major aspects of any read-across exercise, namely assessing similarity and uncertainty. While there can be an over-arching rationale for grouping organic substances based on molecular structure and chemical properties, these similarities alone are generally not sufficient to justify a read-across prediction. Further scientific justification is normally required to justify the chemical grouping, typically including considerations of bioavailability, metabolism and biological/mechanistic plausibility. Sources of uncertainty include a variety of elements which are typically divided into two main issues: the uncertainty associated firstly with the similarity justification and secondly the completeness of the read-across argument. This article focuses on chronic toxicity, whilst acknowledging the approaches are applicable to all endpoints. Templates, developed from work to prepare for the application of new toxicological data to read-across assessment, are presented. These templates act as proposals to assist in assessing similarity in the context of chemistry, toxicokinetics and toxicodynamics as well as to guide the systematic characterisation of uncertainty both in the context of the similarity rationale, the read across data and overall approach and conclusion. Lastly, a workflow for reporting a read-across prediction is suggested.

Read-across is an alternative approach exploited to address information requirements for risk assessment and for regulatory programmes such as the European Union's REACH regulation. Whilst read-across approaches are accepted in principle, difficulties still remain in applying them consistently in practice. Recent work within Cefic LRI and ECETOC attempted to summarize the state-of-the-art and identify some of the barriers to broader acceptance of read-across approaches to overcome these. Acceptance is undoubtedly thwarted partly by the lack of a systematic framework to characterize the read-across justification and identify the uncertainties particularly for complex regulatory endpoints such as repeated-dose toxicity or prenatal developmental toxicity. Efforts are underway by the European Chemical's Agency (ECHA) to develop a Read-Across Assessment Framework (RAAF) and private sector experts have also considered the development of a similar framework. At the same time, mechanistic chemical categories are being proposed which are underpinned by Adverse Outcome Pathways (AOPs). Currently such frameworks are only focusing on discrete organic substances, though the AOP approach could conceivably be applied to evaluate more complex substances such as mixtures. Here we summarize the deliberations of the Cefic LRI read-across team in characterizing scientific confidence in the development and evaluation of read-across.

There are currently several factors driving a move away from the reliance on in vivo toxicity testing for the purposes of chemical safety assessment. Progress has started to be made in the development and validation of non-animal methods. However, recent advances in the biosciences provide exciting opportunities to accelerate this process and to ensure that the alternative paradigms for hazard identification and risk assessment deliver lasting 3Rs benefits, whilst improving the quality and relevance of safety assessment. The NC3Rs, a UK-based scientific organisation which supports the development and application of novel 3Rs techniques and approaches, held a workshop recently which brought together over 20 international experts in the field of chemical safety assessment. The aim of this workshop was to review the current scientific, technical and regulatory landscapes, and to identify key opportunities towards reaching these goals. Here, we consider areas where further strategic investment will need to be focused if significant impact on 3Rs is to be matched with improved safety science, and why the timing is right for the field to work together towards an environment where we no longer rely on whole animal data for the accurate safety assessment of chemicals.

As offshore facilities are growing in size, number and complexity so only the fire and explosion risk. This study is focused on modelling of fire risk for range of accident scenarios. Natural gas one of the common hydrocarbon produced in offshore facilities could cause variety of fires such as pool fire, jetfire, fire ball and flash fire. Two commonly occurring scenarios jetfire and fireball are considered here. These fires scenarios were evaluated with two different fire modelling approaches, solid flame model and Computational Fluids Dynamics (CFD) model. In CFD models, Pyrosim and Fire Dynamic Simulator (FDS) tool are used. In both approaches radiative heat flux from the fire is determined to assess the risk. Furthermore, the radiative heat flux is also used to define the impact to human for different degree of burns. Results from both approaches are compared to determine accuracy in fire risk modelling. Additionally, the CFD based fire models are validated incident report available through the U.S Chemical Safety Board (CSB). The results showed that the CFD method provided reasonably accurate results and thus recommended for offshore fire risk modelling.

Guidelines of the United States Environmental Protection Agency (EPA, 1991) and the International Programme on Chemical Safety (IPCS, 2005) suggest two different default positions for dosimetric extrapolation from experimental animals to humans when the dosimetry of the critical effect is not known. The default position of EPA (1991) for developmental toxicity is to use peak concentration (or Cmax) for this dosimetric extrapolation. In contrast, IPCS (2005, page 39) states its default position for dosimetric choice in the absence of data is to use the area under the curve (or AUC). The choice of the appropriate dose metric is important in the development of either a Chemical Specific Adjustment Factor (CSAF) of IPCS (2005) or a Data Derived Extrapolation Factor (DDEF) of EPA (2014). This research shows the derivation of a DDEF for developmental toxicity for perfluorooctanoate (PFOA), a chemical of current interest. Here, identification of the appropriate dosimetric adjustment from a review of developmental effects identified by EPA (2016) is attempted. Although some of these effects appear to be related to Cmax, most appear to be related to the average concentration or its AUC, but only during the critical period of development for a particular effect. A comparison was made of kinetic data from PFOA exposure in mice with newly available and carefully monitored kinetic data in humans after up to 36 weeks of PFOA exposure in a phase 1 clinical trial by Elcombe et al. (2013). Using the average concentration during the various exposure windows of concern, the DDEF for PFOA was determined to be 1.3 or 14. These values are significantly different than comparable extrapolations by several other authorities based on differences in PFOA half-life among species. Although current population exposures to PFOA are generally much lower than both the experimental animal data and the clinical human study, the development of these DDEFs is consistent with current guidelines of both EPA (2014) and IPCS (2005).

Rapidly evolving technological methods and mechanistic toxicological understanding have paved the way for new science-based approaches for the determination of chemical safety in support of advancing public health. Approaches including read-across, high-throughput screening, in silico models, and organ-on-a-chip technologies were addressed in a 2017 workshop focusing on how scientists can move effectively toward a vision for 21st century food safety assessments. The application of these alternative methods, the need for further development of standardized practices, and the interpretation and communication of results were addressed. Expert presentations encompassed regulatory, industry, and academic perspectives, and the workshop culminated in a panel discussion in which participants engaged experts about current issues pertaining to the application of alternative methods in toxicological testing for food safety assessments.

To satisfy REACH requirements a high number of data on chemical of interest should be supplied to the European Chemicals Agency. To organize the various kinds of information and help the registrants to choose the best strategy to obtain the needed information limiting at the minimum the use of animal testing, integrated testing strategies (ITSs) schemes can be used. The present work deals with regulatory data requirements for assessing the hazards of chemicals to the aquatic pelagic environment. We present an ITS scheme for organizing and using the complex existing data available for aquatic toxicity assessment. An ITS to optimize the choice of the correct prediction strategy for aquatic pelagic toxicity is described. All existing information (like physico-chemical information), and all the alternative methods (like in silico, in vitro or the acute-to-chronic ratio) are considered. Moreover the weight of evidence approach to combine the available data is included.

A tragic explosion resulting from a runaway chemical reaction occurred at the T2 Laboratories, Inc. facility in December 2007. The U.S. Chemical Safety Board (CSB) completed an incident investigation of the T2 explosion, identifying the root cause as a failure to recognize the runaway reaction hazard associated with the chemical it was producing. Understanding the consequences of process upset conditions is critical to determine risk. This paper will focus on lessons learned from this incident including a comprehensive hazard assessment for reactive chemicals as well as proper collection and application of adiabatic calorimetry data to characterize the chemical reaction and determine appropriate mitigation strategies. Examples will be provided to establish safer operating conditions, implement safeguards and reduce the overall risk.

At the request of the U.S. Chemical Safety and Hazard Investigation Board (CSB), we examined some of the possible uses of the process safety event metrics proposed by the American Petroleum Institute and published as ANSI/API Recommended Practice 754. We examined many sources to try to estimate what the likely number of Tier 1 and Tier 2 process safety events would be at refineries. Then we calculated the statistical power that would be available to compare rates, both over time and across facilities and firms. As Tier 1 and Tier 2 are defined, it appears that the event frequencies estimated for U.S. refineries (i.e., 0.12 per 100 employees for Tier 1 and 0.26 for Tier 2) would make it unlikely that even two-fold differences in the rates would be statistically significant, except at large refineries with several thousand workers.

To advance the utility and predictability of safety evaluation, an integrated approach that relies on all existing knowledge to understand how agents perturb normal biological function or structure is needed to progress more focused evaluation strategies. The mode of action (MOA)-human relevance framework developed by the International Program for Chemical Safety and The International Life Sciences Institute provides a useful analytical approach where different lines of evidence (e.g., in vitro, in vivo) can be organized, linked, and integrated at different levels of biological organization into a more efficient, hypothesis-driven approach to safety evaluation. This framework provides a weight-of-evidence approach based on considerations for causality (as originally articulated by Bradford Hill), including dose response and temporal concordance, consistency, specificity, and biological plausibility and coherence. Once an animal MOA and its key events are established, qualitative and quantitative comparisons between experimental animals and humans are made based on the key events. This comparison enables a conclusion as to whether the MOA is likely operative in humans and, if so, whether it can result in a more refined hazard and dose-response assessment. This framework provides an important tool to promote and formalize the use of MOA data in safety evaluation regardless of whether the information comes from traditional or novel approaches, such as those recommended by the NRC in its 2007 report "Toxicity Testing in the 21st Century," which recommends moving away from traditional approaches of measuring adverse endpoints by using newer technologies to identify ways agents may considerably perturb cellular pathways to produce their toxicity.

This paper describes a framework for the risk assessment of combined exposure to multiple chemicals based on and developed subsequent to the World Health Organization/International Programme on Chemical Safety Workshop on Aggregate/Cumulative Risk Assessment (Combined Exposures to Multiple Chemicals) held in 2007. The framework is designed to aid risk assessors in identifying priorities for risk management for a wide range of applications where co-exposures to multiple chemicals are expected. It is based on a hierarchical (phased) approach that involves integrated and iterative consideration of exposure and hazard at all phases, with each tier being more refined (i.e., less cautious and more certain) than the previous one, but more labor and data intensive. It includes reference to predictive and probabilistic methodology in various tiers in addition to tiered consideration of uncertainty. The paper also annexes two case studies that have been developed to test and refine the framework.

This study attempted to evaluate the inspection effectiveness of the U.S. OSHA process safety management (PSM) standard using statistical correlation test. A total of 6578 citations of past 1277 OSHA PSM inspections from 1992 to 2006 were quantitatively compared with the findings of the U.S. Chemical Safety and Hazard Investigation Board (CSB) investigations on root and contributing causes of 19 major chemical accidents. Nonparametric Spearman's coefficient of rank correlation tests showed a moderately strong agreement between OSHA PSM inspection citations and CSB findings at p

Background In 2005, the World Health Organization (WHO) – International Programme on Chemical Safety reevaluated the toxic equivalency factors (TEFs) for dioxin-like compounds and made changes that affect the calculation of the total toxic equivalent (TEQ). The impact of these changes on the TEQs for human blood and abiotic matrices such as soil and household dust has not been widely assessed or reported. Methods and results Using a major exposure study which examined blood, household dust, and soil levels of dioxin-like compounds in several regions of Michigan, we found the mean total TEQ was significantly reduced by 26%, 12% and 14% for serum, household dust, and soil, respectively, when the TEQ was based on the 2005 TEFs compared to the 1998 TEFs. The decrease in the serum total TEQ was largely due to the down-weighting of the TEFs for the majority of mono–ortho PCBs. In contrast, the decrease in the soil total TEQ was mostly due to the down-weighting of the TEF for 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) (1998 TEF = 0.5, 2005 TEF = 0.3). For household dust, the decrease in total TEQ was not due to any single TEF but was due to small changes in a number of compounds. There was a dramatic decrease (−88%) in the mean and 95th percentile for mono–ortho PCB TEQ due to the 2005 TEFs. Discussion These findings suggest that comparisons between studies based on the TEQ–WHO98 and TEQ–WHO05 may need to consider an appropriate conversion factor to assure comparability. Furthermore, the changes in TEFs may have impact in locations where regulations of soil contamination are triggered by specific TEQ levels.

The past 50 years have seen rapid development of new building materials, furnishings, and consumer products and a corresponding explosion in new chemicals in the built environment. While exposure levels are largely undocumented, they are likely to have increased as a wider variety of chemicals came into use, people began spending more time indoors, and air exchange rates decreased to improve energy efficiency. As a result of weak regulatory requirements for chemical safety testing, only limited toxicity data are available for these chemicals. Over the past 15 years, some chemical classes commonly used in building materials, furnishings, and consumer products have been shown to be endocrine disrupting chemicals – that is they interfere with the action of endogenous hormones. These include PCBs, used in electrical equipment, caulking, paints and surface coatings; chlorinated and brominated flame retardants, used in electronics, furniture, and textiles; pesticides, used to control insects, weeds, and other pests in agriculture, lawn maintenance, and the built environment; phthalates, used in vinyl, plastics, fragrances, and other products; alkylphenols, used in detergents, pesticide formulations, and polystyrene plastics; and parabens, used to preserve products like lotions and sunscreens. This paper summarizes reported indoor and outdoor air concentrations, chemical use and sources, and toxicity data for each of these chemical classes. While industrial and transportation-related pollutants have been shown to migrate indoors from outdoor sources, it is expected that indoor sources predominate for these consumer product chemicals; and some studies have identified indoor sources as the predominant factor influencing outdoor ambient air concentrations in densely populated areas. Mechanisms of action, adverse effects, and dose–response relationships for many of these chemicals are poorly understood and no systematic screening of common chemicals for endocrine disrupting effects is currently underway, so questions remain as to the health impacts of these exposures.