Building Blocks Towards a Proportionate Chemicals Policy With a Focus on the Netherlands.

In this contribution, we propose that 'sound' government policy should be characterised by a proportionate, integral vision with due consideration to tradeoffs between social costs and benefits. This principle also applies to government policy regarding the protection of workers from exposure to chemicals. It should be taken into account that having a job is a huge health benefit.

Nitrogen Critical Loads: Critical Reflections on Past Experiments, Ecological Endpoints, and Uncertainties.

Nitrogen Critical Loads (NCL), as purported ecological dose-response outcomes for nitrogen deposition from anthropogenic sources, play a central role in environmental policies around the world. In the Netherlands, these NCL are used to assess, via calculations using the model AERIUS, to what extent NCL are exceeded for different habitats as a result of different sources such as industry, agriculture, traffic. NCL are, however, not well defined, and are subject to hitherto unrecognized forms of uncertainty.

Reflections on chemical risk assessment or how (not) to serve society with science.

In this paper, we want to shed light on the demand for chemical and toxicological data growing ever more faster than science can supply and other aspects of assessing chemical risks, including the demand for 'ever greater safety'. The treatise that follows is on the one hand rooted in well-established toxicological theory and on the other hand utilises emerging toxicological insights. Both theoretical conceptions and empirical substantiations are discussed to build up a perspective that produces an outlook on innovation and proliferates insights into our inexorable and invaluable exposure to 'the chemical'.

Tradeoffs of chemicals regulation - The science and tacit knowledge of decisions.

In this paper, we want to shed light on the tradeoffs of chemicals regulation. We will discuss two types of tradeoffs: the social-economic impacts of regulation such as cost-induced fatalities and the tradeoffs between 'old' and 'new' chemicals, that is the established chemicals in industry and society deemed in need of replacement with 'new' chemicals. We will show that the progression from the science of chemicals risk assessment to regulation requires the science of regulatory (economic) analyses, with added insight from the philosophy of science.

A Short Critique on the Stance of the Netherlands Food and Consumer Product Safety Authority on Melamine Polymer Formaldehyde Exposures.

In February 2021, the Netherlands Food and Consumer Product Safety Authority came out with their risk assessment on formaldehyde exposure from melamine crockery with bamboo fiber to especially young children. In this short commentary, I will critique their assessment of this type of food-contact material (FCM). The main flaws are at least: (i) absence of a proper valuation of the available principal scientific literature yielding a biased risk assessment; (ii) discounting the endogenous formaldehyde formation that outweighs background exposure substantially; (iii) ad hoc positing of an unjustifiable and unfounded low background exposure levels to formaldehyde whereby risks of exposure to melamine formaldehyde is grossly exaggerated.

Chloroquine commonly induces hormetic dose responses.

The use of chloroquine in the treatment of COVID-19 has received considerable attention. The recent intense focus on this application of chloroquine stimulated an investigation into the effects of chloroquine at low doses on highly biologically-diverse models and whether it may induce hormetic-biphasic dose response effects. The assessment revealed that hormetic effects have been commonly induced by chloroquine, affecting numerous cell types, including tumor cell lines (e.

Immunomodulation Through Low-Dose Radiation for Severe COVID-19: Lessons From the Past and New Developments.

Low-dose radiation therapy (LD-RT) has historically been a successful treatment for pneumonia and is clinically established as an immunomodulating therapy for inflammatory diseases. The ongoing COVID-19 pandemic has elicited renewed scientific interest in LD-RT and multiple small clinical trials have recently corroborated the historical LD-RT findings and demonstrated preliminary efficacy and immunomodulation for the treatment of severe COVID-19 pneumonia. The present review explicates archival medical research data of LD-RT and attempts to translate this into modernized evidence, relevant for the COVID-19 crisis.

The EPA Cancer Risk Assessment Default Model Proposal: Moving Away From the LNT.

This article strongly supports the Environmental Protection Agency proposal to make significant changes in their cancer risk assessment principles and practices by moving away from the use of the linear nonthreshold (LNT) dose-response as the default model. An alternate approach is proposed based on model uncertainty which integrates the most scientifically supportable features of the threshold, hormesis, and LNT models to identify the doses that optimize population-based responses (ie, maximize health benefits/minimize health harm). This novel approach for cancer risk assessment represents a significant improvement to the current LNT default method from scientific and public health perspectives.

The Integration of LNT and Hormesis for Cancer Risk Assessment Optimizes Public Health Protection.

This paper proposes a new cancer risk assessment strategy and methodology that optimizes population-based responses by yielding the lowest disease/tumor incidence across the entire dose continuum. The authors argue that the optimization can be achieved by integrating two seemingly conflicting models; i.e.

Cancer risk assessment: Optimizing human health through linear dose-response models.

This paper proposes that generic cancer risk assessments be based on the integration of the Linear Non-Threshold (LNT) and hormetic dose-responses since optimal hormetic beneficial responses are estimated to occur at the dose associated with a 10(-4) risk level based on the use of a LNT model as applied to animal cancer studies. The adoption of the 10(-4) risk estimate provides a theoretical and practical integration of two competing risk assessment models whose predictions cannot be validated in human population studies or with standard chronic animal bioassay data. This model-integration reveals both substantial protection of the population from cancer effects (i.

"You Can't Always Get What You Want" - Linearity as the Golden Ratio of Toxicology.

Referring to the Golden Ratio (i.e. expressed in the Fibonacci sequence) in nature and art, we conclude that toxicology knows its own Golden Ration, namely linearity.

Antibiotics exposure and health risks: chloramphenicol.

The antibiotic chloramphenicol (CAP) is banned from food production. Besides being a medicinal product, CAP is also a natural product, produced by Streptomyces Venezuelae. The lack of scientific data hampers setting of an Acceptable Daily Intake (ADI).

Nutrition and health – transforming research traditions.

In this contribution, we show that current scientific methodologies used in nutrition science and by regulatory agencies, such as the randomized control trial, limit our understanding of nutrition and health as they are to crude to capture the subtle pleiotropic nature of most nutrients. Thereby, regulatory agencies such as the European Food Safety Authority curb the development of scientific knowledge and industrial innovations within the nutritional field. In order to develop insights into the health impact of certain food and food-components, we need to realize that health is adaptation set within a homeostatic range.

Of reductionism and the pendulum swing: connecting toxicology and human health.

In this contribution we will show that research in the field of toxicology, pharmacology and physiology is by and large characterised by a pendulum swing of which the amplitudes represent risks and benefits of exposure. As toxicology usually tests at higher levels than the populace routinely is exposed to, it reverts to mostly linear extrapolative models that express the risks of exposure, irrespective of dosages, only. However, as we will explicate in two examples, depending on dosages, it is less easy to separate risks and benefits than current toxicological research and regulatory efforts suggest.

Chemicals and health - thought for food.

In our contribution we concisely question and answer some basic notions on food, health, and safety. We show that for some food components such as flavonoids, a whole range of small toxicological effects that have been uncovered the last decade on the whole confer benefits to human health. This development underlines the notion that health is adaptation with respect to the exposures humans experience when consuming food.

Why RDAs and ULs are incompatible standards in the U-shape micronutrient model: a philosophically orientated analysis of micronutrients' standardizations.

Risk assessments of micronutrients are carried out in the customary deficiency-excess model. It is regarded as straightforward and unambiguous. Nevertheless, it is a problematic amalgamation of two different and to a certain extent contrasting perspectives on risk and science that we will criticize in this contribution.

Hormesis in precautionary regulatory culture: models preferences and the advancement of science.

The article focuses on flaws in the actual approaches of exposure to a chemical of recipient organisms. It demonstrates the excessive use of arguments based on adverse effects and underlines the necessity to take adaptive effects seriously. Regulators are invited to rethink their inclination to the 'When in doubt, keep it out.

Food supplements and European regulation within a precautionary context: a critique and implications for nutritional, toxicological and regulatory consistency.

In this paper, we review European legislation in the field of micronutrient food supplements and find it wanting. It is shown that the precautionary principle, embedded in European food legislation, pre-empts innovative developments in this field. In view of the scientific advances in micronutrients research, we subsequently critique the precautionary perspective and propose a novel outlook on micronutrients food supplements regulation.