Plenary Lectures 2017-11-27T11:52:10+00:00

CTDC 10
12th SCT

April 18-21, 2018. Belgrade, Serbia

Plenary Lectures

Opening Lecture:

State of science and profession of Toxicology on the African Continent: Lessons learned from challenges, advancements, and future developments

M Gulumian1,2

1National Institute for Occupational Health (NIOH), P O Box 4788, Johannesburg 2000, South Africa

2Haematology and Molecular Medicine Department, School of Pathology, University of the Witwatersrand

Corresondence: mary.gulumian@nioh.nhls.ac.za

Progress in social, political and economic developments experienced by countries within the African continent have also produced challenges in addressing adverse impacts on human health and the environment. The unambiguous role played by toxicologists in developed countries in addressing similar challenges is a foregone conclusion. As yet, reliance on toxicologists in addressing these very challenges may not be the norm in different African countries. The reasons being multi factorial: toxicology is a neglected profession where it is simply not part of the education curriculum, misconception on the recognition of toxicology as a separate scientific discipline, and finally lack of understanding of the role and functions of a toxicologist where the stress should be more on prediction and prevention through risk assessment rather than on a mere confirmation of toxicity.

The establishment of number of toxicological societies in different African countries has helped in addressing some of these challenges. In developed countries risk assessment has grown to a sufficient stature to assess hazard, estimate risk as well as offer rational safe management of these risks. The toxicological societies within these African countries have taken this approach seriously and have embarked in number of training opportunities as well as post graduate courses on the topic. They have also enabled toxicology to be recognised as a profession but most importantly, have succeeded in changing the perception on the role and functions of toxicologists in addressing human health and the environment.

Challenges do however exist in providing opportunities for toxicologists in these countries to contribute in setting of more relevant standards in occupational and environmental surrounding as well as their involvement in regulatory aspects in registration of pesticides pertaining to this sub-discipline of toxicology. Future developments on the continent are therefore aimed at directing efforts to fulfill this important role of toxicologists on the African continent through providing training to the toxicologists and also communication with governmental agencies.

Keywords: perception of toxicology, toxicology neglected profession, training needs, challenges faced by toxicologists

Introduction to the Concept of “Signal Toxicity”

Jun Kanno 1,2

1 Japan Bioassay Research Center, Japan Organization of Occupational Health and Safety

2 Division of Cellular and Molecular Toxicology, National Institute of Health Sciences.

The “Silent Spring” by Rachel Carson (1962) had established the basis for, and the “Our Stolen Future” by Theo Colbone, Dianne Dumanoski and John Peterson Myers (1996) had coined the concept of “Endocrine Disrupting Chemicals” with its mechanistic plausibility to all living organisms. And it took some time to realize that the plausibility is backed by the paradigm of receptor-mediated toxicity or in other words “signal toxicity”.

In classical toxicology, a toxic substance reaches the target molecule and induces malfunction. Such targets are enzymes, lipid membranes, DNA, and other components in the cell. In case of signal toxicity, a chemical binds to a receptor. After that, the chemical itself is not important. The signal from the receptor initiates a cascade of molecular events that leads to various changes in the cells and organs. When the signal is abnormal in terms of quality, intensity and timing, the signal will induce adverse effects to cells and organs. The target would be not only endocrine system including reproductive, but also immune, and neuronal systems. The dose-response characteristics and the dose-range will depend on the signaling system of concern. If the signaling system is used for organogenesis and its functional maturation, there would be a critical period in developmental phase that the disturbance of such signals may leave irreversible changes to the organ.

Here, experiments to illustrate the “early exposure – late effect” at a so-called “low dose range” and related project on transcriptomics will be presented for further discussion on this matter.

Keywords: signal toxicity, receptor mediated toxicity, endocrine disrupting chemicals, perinatal exposure, Percellome Project

The Search for Safe Replacements for Endocrine Disrupting Chemicals

Barbara F. Hales1, Bernard Robaire1,2

1Department of Pharmacology & Therapeutics, 2Department of Obstetrics & Gynecology, McGill University, Montreal, QC, Canada H3G 1Y6

Correspondence: barbara.hales@mcgill.ca

 

Some of the diverse synthetic chemicals associated with our modern lifestyle have unintended adverse influences on human health, affecting hormone production or action, and thus acting as endocrine disrupting chemicals (EDCs). Polybrominated diphenyl ether (PBDE) flame retardants, phthalate plasticizers, and bisphenol A (BPA), an epoxy resin ingredient, are EDCs. Studies with animals and cells have provided evidence for associations between PBDE exposures and adverse outcomes. Human studies demonstrate that PBDE exposures are associated with adverse effects on neurobehavior and an increase in cryptorchidism. Phthalates have well documented anti-androgenic effects while BPA exposure is associated with estrogenic activity. Many governments have restricted the uses of these chemicals due to their adverse effects, creating a “market gap”. We are now discovering that chemicals introduced as replacements may not be safer than the “legacy” substances. BPA analogues, with similar chemistry, may have similar or greater toxicity than BPA. Organophosphates are “emerging” as the “new” flame retardants; using cell and limb bud cultures we have shown that some of these chemicals have effects similar to or greater than PBDEs. In collaboration with colleagues in Chemical Engineering we have identified novel “green” alternative plasticizers with a promising profile. Improvements in our assessment of alternatives are needed to ensure that strategies to identify replacements that are safer and have a reduced environmental impact will be embedded in society in the future.

Supported by the CIHR Institutes of Human Development, Child and Youth Health and of Population and Public Health. BFH and BR are James McGill Professors.

 

Keywords: flame retardants, phthalates, bisphenols, reproductive toxicity, developmental toxicity

From Pre-marketing Studies and Authorization Dossiers to New Prospects for Pesticide Risk Assessment in Rural Enterprises

Claudio Colosio, Stefan Mandic-Rajcevic, Federico Maria Rubino

Department of Health Sciences of the University of Milan and International Centre for Rural Health of the S. Paolo Hospital, Italy

Correspondence: claudio.colosio@unimi.it

 

The role of pesticides in the modern society has been strengthened by the need for higher yield in food production and the ongoing battle against vector borne diseases in public health. Nevertheless, the toxicity of these chemicals is not fully specific to target organisms, thus posing a potential health threat to humans. In this frame, risk assessment and management are fundamental. In the occupational settings, variability of meteorological conditions, use of different concentrations of variable mixtures, and significant variations in the application times and modalities make this task very complicated, making necessary proposing novel approaches for conducting “in field” preventive activities. The amount of information collected during the process of authorization of a new active ingredient is unique, with a size similar of the one available for human drugs. Therefore, a possible way forward for risk assessment is represented by a better exploitation in the post-marketing phase of the data used for the registration process, combined with the data collected in real-life field studies usable for refining and validate the risk hypothesis generated through modelling. In particular, parameters such as Acceptable Operator Exposure Level (AOEL), acute reference dose (ArD) as well data regarding skin absorption, metabolism and relevant metabolites in animals can find use in the conduction of risk assessment activities in agricultural enterprises, through the creation of new tools for exposure and risk assessment. Such tool are usable even without conducting complicated and expensive measures, and therefore are adequate for the needs of small and medium sized agricultural enterprises.

 

Keywords: exposure assessment, biological monitoring, modeling, field studies, small and medium-sized enterprises

Communications in the Area of Toxicology: a Challenging Task?

Lucia de Luca

European Food Safety Authority

In her talk Lucia will look at the characteristics of communicating risks and in particular those in the area of toxicology. The talk with look at why should experts engage in communication and what are the challenges they should pay attention to? Specific focus will be devoted to todays’ societal background against which toxicological concepts and scientific work needs to be communicated and what role can scientists and toxicologists play in ensuring effective risk communication.

 

Keywords: risk, communication, information, engagement, trust