Workshops 2018-03-28T07:29:08+00:00

CTDC 10
12th SCT

April 18-21, 2018. Belgrade, Serbia

Plenary Workshop

TOXICOLOGY DATA AND ONLINE TOOLS: AVAILABILITY, SEARCH STRATEGIES, OPEN DATA, AND REPRODUCIBILITY

Chair: Philip Wexler, wexlerp@mail.nlm.nih.gov

National Library of Medicine,

Toxicology information in the form of online databases and related data resources is widespread.  The challenge is knowing what is available, how to fit the right resource to the need, and to recognize what may be missing.  This session will address the issue by offering an overview of two extensive portals to toxicological data, followed by a practical look at how to access information to answer particular questions, and conclude with ways to enhance data repositories in the interests of transparency and reproducibility.  The session will begin by highlighting two major toxicology data portals, the U.S. National Library of Medicine’s TOXNET system and the OECD’s eChemPortal, together covering a vast array of both references to toxicological literature and data, and free to the public.  Among TOXNET’s many databases are the Hazardous Substances Data Bank (HSDB), containing toxicologically oriented data on some 6,000 chemicals, and TOXLINE, a bibliographic file of over 4 million references.  eChemPortal draws from a multiplicity of sources offering data on chemical use, hazard, exposure, and risk information.  Another presentation looks at the particular question of identifying reliable information on workplace chemical exposures and offers guidance.  The two concluding papers take different but related approaches to look at the broader issues of research and publication and how a greater transparency can enhance the credibility and reliability of results.  One of these focuses on the importance of reproducibility and data sharing while the other highlights the increasing move to open data, both within the context of toxicological research.

 

Keywords: TOXNET, eChemPortal, occupational health data, reproducibility, open data

The US National Library of Medicine’s TOXNET System and Other Toxicology Information Resources

 

Philip Wexler1

1National Library of Medicine

Correspondence: wexlerp@mail.nlm.nih.gov

The US National Library of Medicine’s (NLM) Toxicology Information Program, established in 1967, evolved into today’s Toxicology and Environmental Health Information Program (TEHIP).  TEHIP offers a comprehensive and globally accessible online portal to free information on toxicology and allied disciplines.  These include databases, bibliographies, tutorials and other scientific and consumer-oriented resources.  Among its most widely consulted databases, offered via the TOXNET system, are HSDB (Hazardous Substances Data Bank), a peer-reviewed file covering some 6,000 chemicals with information on their human health effects, emergency medical treatment, animal toxicity studies, environmental fate/exposure, chemical/physical properties, and much more and TOXLINE (Toxicology Literature Online) containing over 4 million references to technical literature on the biochemical, pharmacological, physiological, and toxicological effects of drugs and other chemicals and ChemIDplus, a chemical dictionary of over 400,000 chemical, including names, synonyms, structures, toxicity data, and links to additional information such as regulatory lists.  Specialized databases cover topics such as drugs and lactation (LactMed), developmental and reproductive toxicology (DART), toxic releases (TRI), household products (Household Products Database), occupational exposures (Haz-Map), and risk assessment (IRIS and TRI).  Radiation Emergency Medical Management (REMM) and Chemical Hazards Emergency Medical Management (CHEMM) and two tools offered by TEHIP for the emergency response community.  Resources such as ToxTown and ToxMystery are designed specifically for students and educators.  TEHIP also provides links to information on a diverse range of subjects in environmental health and toxicology, disasters, chemicals, drugs, and special populations.  This presentation will also touch upon other global toxicology databases.

Keywords: TOXNET, databases, informatics, NLM, online searching

eChemPortal – The Global Portal to Information on Chemical Substances

 

Sally de Marcellus and Bob Diderich

 Organisation for Economic Co-operation and Development (OECD)

Correspondence: sally.demarcellus@oecd.org; bob.diderich@oecd.org

In a continuous effort to build chemicals management capacity to protect human health and the environment, the Organisation for Economic Co-operation and Development (OECD), in cooperation with the European Chemicals Agency and with contributions from governments, international organisations, non-governmental organisations and the chemical industry, developed an Internet portal which provides access world-wide to regulatory relevant chemical information.

eChemPortal is an efficient instrument for finding and accessing hazard and risk assessments, chemical property data sets, classification results, and exposure and use information on a chemical substance across existing and new industrial chemicals, pesticides, and biocides.

Searches by substance identity, property and effects (physical-chemical properties, environmental fate and behaviour, ecotoxicity, and toxicity), or classifications lead to the websites of multiple data sources, targeting the location of the specific information searched. Searches by classifications according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) also display a table view for a specific chemical of classifications which have been reviewed and made available by a regulatory body or intergovernmental organisation.

The OECD encourages use of the eChemPortal and encourages regulatory authorities to make chemical information freely available on the Internet and via eChemPortal.

Disclaimer: The opinions expressed and arguments employed herein are those of the authors and do not necessarily reflect the official views of the OECD or of the governments of its member countries.

 

Keywords: chemical, hazards, environment, health, classification

How to Find Reliable Online Information Regarding Chemical Exposure at Work?

 

Gert van der Laan1,2,3, Pieter van Broekhuizen4, Frank van Dijk1,3,4,5

1 Free University of Amsterdam Medical Centre (VUMC), The Netherlands. International Centre for Rural Health, University of Milano, Italy. 3 Foundation for Learning and Developing Occupational Health (LDOH) 4 University of Amsterdam,  Amsterdam, The Netherlands. 5Arbeits- und Umweltsepidemiologie & Net Teaching, Ludwich-Maximilians-Universität, München, Germany

Corresponence: g.vanderlaan@occmed.eu

Health professionals all over the world dealing with toxicological and occupational hygiene problems often have just basic knowledge of toxicology. They face two main categories of toxicological questions to solve. Substance-oriented questions concerning characterisation of the substance, human exposure and health effects, methods of measuring and monitoring, treatment of adverse health effects or occupational illnesses, prevention and risk-communication. And questions concerning a disease: is this caused by exposure to specific substances and how should this be assessed?

For identification of toxicological and occupational hygiene data a guidance is developed with an overview of relevant, open access databases. The databases are distinguished under different headings:

  • From trade name into generic name to chemical name/ CAS number
  • Searches and search engines for MSDS
  • Chemical data overview for regulatory purposes
  • Chemical profiles of industrial processes
  • Risks assessments documents of chemicals
  • Data on specific chemical classes, such as pesticides, solvents
  • Databases starting from medical endpoints/diseases
  • Bibliographic databases, such as PubMed

The guidance will be integrated in OSH-online and in the update of the book OSH online. How to find reliable information (Van Dijk, Caraballo-Arias).

Several practical issues may be difficult to manage. An example is the practice that workers are often exposed to complex workplace-generated mixtures such as welding fumes, diesel exhaust fumes, dirt and other undefined fumes generated by heating, combustion or machining of materials. Another example is assessing industrial chemicals with limited hazard information. Finally there might be practical problems of dealing with  poor  Internet connections and language issues

Keywords: occupational toxicology, free data-bases, search strategy

The Importance of Open Data in Toxicological Research and Publishing

 

Petar Bulat1,2, Zorica Bulat3, Stefan Mandić-Rajčević4

1 University of Belgrade-Faculty of Medicine, Belgrade Serbia, 2 Serbian Institute of Occupational Health, Belgrade Serbia, 3 University of Belgrade-Faculty of Pharmacy Department of Toxicology “Akademik Danilo Soldatović” Belgrade, Serbia, 4 Department of Health Sciences, University of Milan, Milan Italy

Correspondence: petar.bulat@med.bg.ac.rs

Every year thousands of toxicological studies are performed around the World. These studies are most commonly funded by Governmental, Non-Governmental agencies, Universities, Faculties, and in the last 50 years even more so by funds provided by research funding schemes such as the Horizon 2020 and the Framework Programmes in the European Union, or the National Institutes of Health in the United States. As part of these studies, thousands of experiments and field studies are done, collecting millions of tables of data ranging from genotypes and cell-culture reactions to chemical agents, to epidemiological data on populations from different towns and countries. In addition, governmental agencies and private companies measure a vast amount of parameters regarding the environment. Recently, a very specific risk has come to attention of research funders: the results of a specific research project are published in a peer review journal, thus satisfying the basic requirements of the project call, and the raw data which was collected remains buried (or lost) in the hard-disk of participating researchers. To resolve this situation, many institutions have adopted the „Open Data“ policy, which should allow the data collected by these institutions or projects funded by them to be freely available to use and re-use by others. This philosophy was also adopted by many journals which now allow the authors of published articles to store even the raw data in their online repositories. This new trend, which might soon become a rule in the scientific publishing world, considering there are journals specifically designed to store datasets and study protocols, increases the use of already collected data, facilitates data re-use and new discoveries, but also helps authors achieve a higher impact and recognition than by just publishing their work.

Keywords: research data, raw data sharing, open data policy

Improving the Quality of Toxicological Research Findings Using Modern Principles of Reproducible Research

 

Stefan Mandić-Rajčević, Federico Maria Rubino, Claudio Colosio

Department of Health Sciences of the University of Milan and International Centre for Rural Health of the San Paolo Hospital, Via San Vigilio 43, 20142 Milan, Italy

Correspondence: stefan.mandic-rajcevic@unimi.it

Reproducibility represents the foundation of scientific work and publications, and the materials and methods section in each published article should allow any researcher to repeat the experiment in question and get the same or similar results. Nevertheless, in most scientific papers the data analysis procedure is rarely described well, and it often contains just the basic information on statistical procedures performed. We present all of the basic steps in doing reproducible data analysis, with all the advantages and disadvantages over the non-reproducible methods, on a case study of pesticide exposure and risk assessment. Data is imported from multiple sources (text, excel, access database), and basic description of acquired data, visual and numerical comparison between groups, and modelling of data acquired in real-life studies of pesticide exposure in agriculture are presented. The final products of the data analysis process, tables and figures which are ready for the revision process, are compiled using the R Language and Environment for Statistical Computing and additional packages. Considering the more strict requirements for funding and the increased competition, as well as the slow (but certain) move towards open access, open review and data exchange, doing data analysis the reproducible way will become inevitable in toxicology, as well as other scientific fields. Popularization and training on using free statistical and reproducible research tools should be a priority for young researchers entering this field, as this will result in the improvement of the quality of toxicological research, leading to easier publishing.

 

Keywords: R language, statistics, modeling, pesticide studies

Workshops

ARACHNIDS: FALLACIES, CLINICAL MANIFESTATIONS, DIFFERENTIAL DIAGNOSIS AND MANAGEMENT OF SPIDER BITE AND SCORPION STING

Chair: Bruno Megarbane1, bruno.megarbane@aphp.fr; Co-Chair: Cherylynn Wium2, caw@sun.ac.za

1Department of Medical and Toxicological Critical Care, Lariboisière Hospital, Paris-Diderot University, INSERM UMRS-1144, Paris, France

2Division of Clinical Pharmacology, Stellenbosch University, Cape Town, South Africa

Scorpion sting is an important cause of envenomation in Africa, e.g. Morocco, South Africa and Zimbabwe. Important toxicoepidemiological characteristics of scorpion sting include the clinical presentation of envenomation, characteristics of venomous scorpions and clinical management. In Morocco large numbers of scorpion sting occur, therefore a special surveillance program was implemented together with education and communication to health workers and the public. These measures have shown a decreased in the morbidity and mortality of patients with scorpion sting.  Scorpion antivenom is often available in countries where large numbers of scorpion stings occur.  Timeous administration of antivenom may play an important role however, supportive treatments appear mandatory to efficiently improve patient outcomes.  Evidence for additional antivenom use is still questionable and its cost-effectiveness remains limited.  The evidence in favor or against the clinical usefulness of antivenom will be debated.

The medically important spiders of southern Africa and Europe include the neurotoxic spiders belonging to the genus Latrodectus (widow spiders) and the cytotoxic spiders: the genera Cheiracanthium (sac spiders) and Loxosceles (violin spiders). The Latrodectus species cause a serious neurotoxic syndrome known as latrodectism. Cytotoxic spider bite usually manifests as local pain and erythema.  This may develop into a necrotic ulcer.  Necrotic arachnidism is often a convenient diagnosis for unexplained local tissue injury/dermal necrosis. The spectrum of spider bites in southern Africa are not well documented therefore a retrospective analysis of spider bite using two different data-recording systems of a PIC was conducted in an attempt to improve documentation, identification, diagnosis and management.

Keywords: scorpion sting, antivenom, necrotic arachnidism

Antivenom to Treat Scorpion Sting: Is it Useful?

 

Bruno Mégarbane

Department Medical & Toxicological Critical Care, Paris-Diderot University, Paris, France

Correspondence: bruno.megarbane@lrb.aphp.fr

Scorpion sting represent a major public health issue in almost all continents including resource-limited countries. Scorpion venoms contain low molecular-weight peptides that rapidly distribute and induce catecholaminergic storm, accounting for the clinical consequences. Life-threatening but reversible cardiomyopathy represents the major cause of death, mainly from Old World scorpions. Neutralizing and redistributing the venom from its target may be life-saving if rapidly administered. Although well-done experimental studies have evidenced antivenom contribution to improve survival and reduce toxicity following envenomation by scorpions, its usefulness to treat scorpion-stung patients is still controversial. Time from sting to admission generally limits the utility of antivenom action to prevent mediator release and consequently reduce lethality. Additionally, highly species-specific antivenom is needed but still lacking for Androctonus mauritanicus and australis, the most fatal species in Morocco and Tunisia, respectively; whereas poorly refined antivenom may induce severe side-effects. While supportive treatments appear mandatory to efficiently improve the patient, evidence for the additional contribution of antivenom is still missing. Moreover, its cost-effectiveness remains limited. Since authorities have to rationalize expenses, efforts to decrease scorpion-related lethality should be focused on standardizing supportive care, training professionals, launching information campaigns and implementing clinical audit. Before recommending its use, antivenom efficacy should be established by randomized controlled studies. This lecture will review the evidence in favor or against the clinical usefulness of antivenom going from basic science to bedside indications and use.

 

Keywords: scorpion, envenomation, antivenom, severity assessment, cost-effectiveness

Spider Bite in Southern Africa

 

Cherylynn Wium, Gert Muller

Division of Clinical Pharmacology, Stellenbosch University, Cape Town, South Africa

Correspondence: caw@sun.ac.za

The medically important spiders of southern Africa can be divided into neurotoxic and cytotoxic groups.  The neurotoxic spiders belong to the genus Latrodectus (widow spiders) of which six species occur in southern Africa.  The cytotoxic spiders include the genera Cheiracanthium known as sac spiders (nine species) and Loxosceles, known as violin spiders (six species). The Latrodectus species cause a serious neurotoxic syndrome known as latrodectism.  Symptoms and signs reflect peripheral nervous system stimulation e.g. generalised muscular pain and cramps, a feeling of tightness in the chest, anxiety and profuse sweating with board-like rigidity of the abdomen. This syndrome is well known to mimic other disease states.  The differential diagnosis includes scorpionism, snake bite, acute abdomen, myocardial infarction, alcohol withdrawal syndrome and organophosphate poisoning.  Latrodectus antivenom is available in South Africa and is very effective. Spiders in southern Africa suspected of causing the most cases of necrotic arachnidism include the sac spiders (Cheiracanthium) and the violin spiders (Loxosceles).  Although both are widely distributed, the sac spider is more abundant. Symptoms and signs are similar and usually manifests as local pain and erythema.  This may develop into a necrotic ulcer, often slow to heal. Treatment is symptomatic and supportive, which may include antibiotics.  No antivenom is available.  Necrotic arachnidism is an over-diagnosed clinical entity and is often a convenient diagnosis for unexplained local tissue injury/dermal necrosis.  The clinical picture, differential diagnosis and management of latrodectism and necrotic arachnidism will be discussed and debated.

Keywords: latrodectism, arachnidism, differencial diagnosis, antivenom

Spider Bites in Southern Africa: A Poison Centre Experience

 

Arina du Plessis, Helmuth Reuter

Division of Clinical Pharmacology, Stellenbosch University, Cape Town, South Africa

Correspondence: acedp@sun.ac.za

Worldwide the number of spider bite calls to poison centres are minimal.  Most of the spiders involved in so-called cytotoxic spider bites are not positively identified. Medical important spiders of Southern Africa include the Latrodectus (widow), Cheiracanthium (sac) and Loxosceles (violin) species. The spectrum of spider bites in southern Africa are not well documented.  A retrospective analysis of spider bite was conducted over a 4 year period using the consultation sheets of Tygerberg Poison Information Centre (TPIC), 2013-2014 and data from AfriTox TeleLog, the database of the Poison Information Helpline, Western Cape (PIHWC), a combined TPIC and Red Cross Hospital PIC, 2015-2016. From a total of 34785 cases, only 597 (1.7%) consultations were in connection with spider bites.  Latrodectus sp were involved in 91 (15.2%) cases, but only 52 (57%) of these were positively identified.  Sweating, muscle pain and cramps were the symptoms most often recorded.  Antivenom administration was advised in 34 (37.4%) of the Latrodectus envenomings.  The only spider identified in the cytotoxic group (n=72, 12.1%) was a sac spider.  Most spiders were unidentified (n=398, 66.7%).

Two different data recording systems were analysed in an attempt to improve documentation, identification, diagnosis and management of spider bites.

Keywords: spider spectrum, database, antivenom, documentation, Latrodectus

Scorpion Sting in Southern Africa: The Zimbabwean Experience

 

Dexter Tagwireyi and Louis Gadaga,

Drug and Toxicology Information Service, University of Zimbabwe, Harare, Zimbabwe

Correspondence: dextagwireyi@gmail.com

Scorpion sting continues to be an important cause of envenomation in some parts of Africa, including Zimbabwe. Whilst many stings have not been reported as being fatal in Zimbabwe, there are a number of documented deaths in the southern parts of the country. In this paper, important toxicoepidemiological characteristics of scorpion sting in Southern Africa (as exemplified by Zimbabwe) will be presented. These include the clinical presentation of scorpion envenomation, characteristics of venomous scorpion to be aware of as well as clinical management of scorpion stung individuals.

 

Keywords: Scorpionism, toxicoepidemiology, envenomation

Scorpion Stings in Morocco

 

Naima Rhalem, Rhizlane El Oufir, Ilham Semlali, Rachida Soulaymani-Bencheikh

Poison Control and Pharmacovigilance Centre of Morocco, Rabat, Morocco

Correspondence: nrhalemcap@gmail.com

Objective: In Morocco, A national strategy for stings and scorpion envenomations was setup in 2001, focused on training of health professionals, education and communication to the public and improving management of cases. Indicators of morbidity and mortality were set up to evaluate the strategy. We examine the relevance of the strategy by monitoring the chosen indicators.  Methods: We collect records to study regional and national demographics, economics and evolving features of Scorpion Stings (SS) between first January 2001 and 31 December 2016. Results: Totally, 404 500 cases were reported. Patients were in class I (Simple sting without envenomation) in 91.4%. Cases were admitted to a healthcare facility reflecting envenomation (class II for 7.3% and class III for 1.3% of cases).  Lethality rate in patients with SS varied according to year (0.4% in 2005 to 0.2% in 2016). Envenomation lethality rate in patients with class II and class III was at 5.5 in 2001 and at 2.4% in 2016; the lethality rate by SS in children less than 15 years decreased from 2.1% in 2001 to 0.8% in 2016. Conclusion: Continued improvement in the surveillance of morbidity and mortality from scorpion stings is still necessary to reach zero deaths.

 

Keywords: scorpion stings, Poison control centre, Morocco

PRODUCT STEWARDSHIP AND REGULATORY TOXICOLOGY IN THE OIL AND GAS INDUSTRY

 

Chair: Salmaan Inayat-Hussain, salmaan.inayat@petronas.com

Petroliam Nasional Berhad (PETRONAS) Malaysia 

 

As part of the commitment to SAICM, product stewardship plays a significant role in promoting chemical safety through a sound management of chemicals throughout their lifecycle to ensure that chemicals are produced and used in ways that minimize significant adverse impacts on human health and environment by 2020. This 2020 goal was adopted by the World Summit on Sustainable Development in 2002, as part of the Johannesburg Plan of Implementation. In this respect, developed countries have established chemical regulations and there is now an emerging shift where developing countries are also introducing regulations to ensure governance on the manufacture, import and use of chemicals. This workshop will discuss the current approaches and examples of in the product stewardship and regulatory toxicology especially in the oil and gas industry.

Keywords: Product Stewardship, Regulatory Toxicology, Oil and Gas, Toxicity Testing, Reprotoxins Management

 

Product Stewardship and Regulatory Toxicology in the Oil and Gas Industry

 

Salmaan H Inayat-Hussain

Petroliam Nasional Berhad (PETRONAS), Kuala Lumpur, Malaysia

Correspondence: salmaan.inayat@petronas.com

 

As part of the commitment to SAICM, product stewardship plays a significant role in promoting chemical safety through a sound management of chemicals throughout their lifecycle to ensure that chemicals are produced and used in ways that minimize significant adverse impacts on human health and environment by 2020. This 2020 goal was adopted by the World Summit on Sustainable Development in 2002, as part of the Johannesburg Plan of Implementation. In this respect, developed countries have established chemical regulations and there is now an emerging shift where developing countries are also introducing regulations to ensure governance on the manufacture, import and use of chemicals. The oil industry needs global coordination of GHS activities to promote the development and adoption of technically correct and consistent guidelines for petroleum substances classification. IPIECA developed the GHS guide in 2010 (currently being updated) on the classification and labeling of petroleum substances. This workshop will discuss the current approaches and examples of in the product stewardship and regulatory toxicology especially in the oil and gas industry.

 

Keywords: product stewardship, regulatory toxicology, oil and gas

Regulatory Challenges and Opportunities in the Developing Countries for Petroleum Substances

 

Derek D. Swick

American Petroleum Institute, Washington, DC, USA

Correspondence: swickd@api.org

API will share some of its experience with application of chemical management regulations to petroleum substances. As a U.S.-based organization, API has been involved in development of product stewardship and chemical management frameworks in the U.S., including the 2016 Frank R. Lautenberg Chemical Safety for the 21st Century Act. This presentation will outline how this new U.S. law may serve as a model for other countries that are in the process of designing chemical management regulations. Dr. Swick will also discuss current challenges in development of chemical management requirements, while highlighting opportunities for cooperation and convergence. Examples to be presented include:

  • Implementation of the Globally Harmonized System of Classification and Labeling of Chemicals (GHS) as adopted into the legal frameworks of various countries, including discussion of guidance developed by IPIECA on the classification and labeling of petroleum substances.
  • Opportunities for convergence in “existing” chemical inventories and “new” chemical approval programs, which effectively control what chemicals can be imported or manufactured in a country and which chemicals require government approval before introduction.
  • Regulatory framework models for prioritizing chemicals in commerce for risk evaluation and risk management.
  • Prospects for information sharing and cooperation on risk evaluation processes, and leveraging reputable science-based work, including discussion of mature risk evaluation programs that have evolved in the EU, Canada, the U.S., and other countries.

Keywords: UVCB, chemical management, risk evaluation, prioritization, GHS

Integrated Approaches for Testing and Assessment of Chemicals for Regulatory Decision-making

 

Bob Diderich

Organisation for Economic Cooperation and Development

Correspondence: bob.diderich@oecd.org

Governments are struggling with three competing requirements: (1) assessing and managing the risks of more chemicals in a shorter time, (2) reducing the number of laboratory animals used for the safety testing of chemicals, and (3) increasing the knowledge-base on which to base the risk assessments and reducing their uncertainty.

While traditionally risk assessments are based on a set of predetermined set of standardised laboratory tests, such as OECD Test Guidelines, many of which use laboratory animals, regulatory risk assessors more and more rely on a wide array of information used in a weight of evidence assessment. These so-called Integrated Approaches for Testing and Assessment (IATA) may include results from (Q)SARs, read-across, in vitro, ex vivo and in vivo methods.

While IATAs indeed have the potential to speed up the risk assessment process and to reduce the reliance on test results involving laboratory animals, the integration of different types of data into hazard characterisation may prove to be complex. The OECD has therefore promoted the concept of Adverse Outcome Pathways (AOPs) as a way of organising and integrating results from different types of methods. An AOP is a description of how the interaction of chemicals at the molecular level in a organism triggers adverse effects at the cellular, organ, whole organism or even population level.

The mechanistic knowledge gathered in AOPs can be used to structure and evaluate the existing data available for a chemical from different methods and help decide whether additional targeted data needs to be generated (integrated testing strategy) before a conclusion can bet taken regarding the hazard characterisation of a chemical. In addition, AOPs can be used (1) for the development of (Q)SARs, (2) for grouping chemicals into chemical categories, (3) for interpreting the results from non-standard test methods and (4) for selecting test methods for further standardisation.

Disclaimer: The opinions expressed and arguments employed herein are those of the author and do not necessarily reflect the official views of the OECD or of the governments of its member countries.

Keywords: OECD test guideline, QSAR, adverse outcome pathway

 

A Concawe Perspective on Alternatives to Animal Testing under Regulatory Programmes

 

Hans Ketelslegers

European Petroleum Refiners Association – Concawe division, Brussels, Belgium

Correspondence: hans.ketelslegers@concawe.org

Petroleum substances (PS) are a prototypical example of UVCBs (Unknown or Variable composition, Complex reaction products and Biological materials), which present enormous challenges for science-informed regulatory decision making. Therefore, regulators and industry have a common interest to define a process for (petroleum) UVCBs to ensure that there is no underestimation of hazards and at the same time minimize or eliminate the use of animals in toxicology testing to ensure safe use.

Over the past decades, major advancements have been made in biotechnology that have changed, and are changing, the field of toxicological sciences. Concawe, recognising both the extensive opportunities but also appreciating the current shortcomings of these new technologies, has several ongoing research efforts aiming to progress the risk assessment of petroleum UVCBs – focusing on either directly informing human health hazard assessments (e.g., reprotoxicity and carcinogenicity endpoints) and indirectly by informing and underpinning read-across approaches. Experience with both applications of high content screening tools on PS will be presented, with a particular focus on Cat-App: a multi-year research consortium initiated in 2016 by Concawe, applying high-content screening data to underpin grouping and read-across under regulatory programmes such as REACH.

Overall, an overview will be given of the feasible alternative approaches that are being developed for PS, working towards a more sustainable framework for 21st century human health assessment of PS with a focus on minimizing the reliance on animal testing in regulatory submissions.

Keywords: petroleum substances, UVCB, risk assessment, alternatives to animal testing, in-vitro screening

Management of Reproductive Toxic Chemicals in the Oil and Gas Industry

 

Masao Fukumura1, A Muiz Aziz1, Linda Roberts2 & Salmaan H. Inayat-Hussain1

1Petroliam National Berhad (PETRONAS) Malaysia, 2Chevron Energy Technology Company  (retired)

Correspondence: Masao.fukumura@petronas.com

Oil & gas industry uses hazardous chemicals throughout the value chain beginning from exploration through the final stage of petrochemical manufacturing. Management of hazardous chemicals, including reproductive toxicants, is important to protect workers from adverse health outcomes. This is particularly true with the increase in female workers in our industry, equating to a greater need to manage reproductive hazards for the wellbeing of workers and their offspring.

Management of reproductive health involves an understanding of inherent hazards, exposures, and reproductive risk assessment. Reproductive toxicity, as defined by the Globally Harmonized System (GHS), includes adverse effects on adult reproductive capacity and developmental toxicity in the offspring. Although workplace chemicals may cause reproductive toxicity, a chemical health risk assessment (CHRA), beginning with hazard identification, is an efficient way to protect workers.  A CHRA assesses a chemical’s potential reproductive or developmental hazard and the exposures associated with effects.  Management of reproductive hazards ensures that risks are controlled and practices are protective.

To better understand chemicals used in the energy sector, profiling from 20 upstream and downstream operating units identified approximately 100 chemicals as reproductive toxicants from GHS classifications. A major challenge was inconsistent hazard classification by different suppliers for the same chemical resulting in inconsistent CHRA outcomes. Of note is that only a small percentage of these chemicals have occupational exposure limits based on reproductive endpoints.

This presentation describes an approach to managing reproductive toxicants, highlighting challenges and opportunities in the oil and gas industry.

Keywords:  reproductive toxicity, hazard identification, GHS, chemical health risk assessment