ArticlePDF Available

Abstract

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’. We propose that in toxicology, with the implicit mandatory linear routine of dose-response, there is no tangible scientific drive to understand and unearth the actual empirical dose-response curve for chemicals under scrutiny. This can and should be improved upon as to advance the science of toxicology and to optimise current and future regulatory efforts.
Reections on chemical risk assessment or how (not) to serve society
with science
Jaap C. Hanekamp
a,b,
,Edward J. Calabrese
c
a
Science Department, University College Roosevelt, Middelburg, the Netherlands
b
Department of Environmental Health Sciences, University of Massachusetts, Amherst, USA
c
Department of Environmental Health Sciences, University of Massachusetts, Morrill I, N344, Amherst, MA 01003, USA
HIGHLIGHTS
The demand for toxicological risk as-
sessments is ever-increasing.
The chemical risk assessment paradigm
needs to overcome the natural-synthetic
divide.
Hazard analyses of carcinogens needs to
be replaced by full-on risk assessments.
The available toxicological models are too
simplistic in their linearity.
GRAPHICAL ABSTRACT
abstractarticle info
Article history:
Received 20 April 2021
Received in revised form 11 June 2021
Accepted 13 June 2021
Available online xxxx
Editor: Michael N Moore
Keywords:
Hazard
Risk
Toxicological models
Risk assessment
Safety standards
Organohalogens
In this paper, we want to shed light on the demand for chemicaland 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. We propose that in toxicology, with the implicit man-
datory linear routine of dose-response, there is no tangible scientic drive to understand and unearththe actual
empiricaldose-responsecurve for chemicals underscrutiny. This can and should be improvedupon as to advance
the science of toxicology and to optimise current and future regulatory efforts.
©2021ElsevierB.V.Allrightsreserved.
1. Bridging the natural-synthetic rifta prolegomenon
In the 1970s, a Dutch science showcalled Chemistry is Everywhere
tried to convey the message that, indeed, chemistry is all around us. It
was a brave attempt to introduce the general public to the eld of chem-
istry, which is far less removed from our daily lives than most people
thought back then and still think today. More precisely, we are, to
some extent, part of that same chemistry we study at the same time.
And that brings with it an enigma of substantial proportions.
That enigma, perhaps the word puzzle is more apt, has to do with the
ostensibly unequivocal rift between the so-called the synthetic and the
natural. The latter, natural chemistrysuch as DNA, proteins, glucose,
Science of the Total Environment 792 (2021) 148511
Corresponding author at: Department ofEnvironmentalHealth Sciences,University of
Massachusetts, Amherst, USA.
E-mail address: j.hanekamp@ucr.nl (J.C. Hanekamp).
https://doi.org/10.1016/j.scitotenv.2021.148511
0048-9697/© 2021 Elsevier B.V. All rights reserved.
Contents lists available at ScienceDirect
Science of the Total Environment
journal homepage: www.elsevier.com/locate/scitotenv
... For example, agriculture and urban activities emit nitrogen and phosphorus into lakes, resulting in eutrophication if the input is over the capacity of lakes (Carpenter et al., 1998); while, heavy industrial activities enhanced the burden of heavy metals in the nearby lakes (Kober et al., 1999). The toxic and effects of these pollutants on wildlife and human are complex and nonlinear (Hanekamp and Calabrese, 2021), and these hazards will be enhanced or reduced when some pollutants occur together, which increase the difficulties to set up a simple frame to evaluate the hazards of pollutants in lakes. ...
... It means that the exposure of biota on the pollutants are site-specific. Apparently, zoning the risk regions based on the combined hazard of pollutants is a key processes to assessing the risks of pollutants in lakes (Hanekamp and Calabrese, 2021). ...
Article
Owing to the complexity of sources and nonlinear dose-response relationship, evaluating the combined risks of pollutants in lakes remains a considerable challenge. In this study, we developed chose a non-parametric risk assessment method with source diagnostic and spatial interactions (LISA analysis) between the pollutants was developed for zoning the risks of combined pollution. Taihu Lake was chosen as the studied region, and the heavy metals and polycyclic aromatic hydrocarbons (PAHs) in the sediments were observed to test this method. Results showed that the developed method distinguished the “hot spots” of pollution in the eastern and northern Taihu Lake, and more than 50% pollutants were attributed to the combustion of petroleum fossil fuels. The main risk control area for heavy metals is mostly distributed in western Taihu Lake, accounting for 22.5% of the total area, while that for PAHs accounts for the smallest proportion, at only 3.4% of the total area. This study shows that the spatial interaction between pollutants could be a useful tool for evaluating the combined risks of pollutants, which can also provide better decision support for lake risk management.
... The risk assessment method is used to characterize risk from exposure to toxic substances. It includes four steps: hazard identification, hazard characterization (related term: dose-response relationship), exposure assessment, and risk characterization (Hanekamp and Calabrese 2021). Since the first two phases are well known and primarily described in the introduction section for selected air pollutants, the following steps are exposure assessment and carcinogenic and noncarcinogenic risk characterization. ...
Article
Full-text available
With global urbanization and industrialization, air pollution has become an inevitable problem. Among air pollutants, toxic metals bound to particulate matter (PM) have a high hazardous potential, contributing to the development of several diseases, including various types of cancer. Due to PM pollution, Serbia is considered to be among the most polluted countries in Europe. Therefore, the objective of the study was to assess and characterize the non-carcinogenic and carcinogenic risks of children’s and adults’ exposure to metal(oid)s (Pb, Cd, Ni, and As) bound to PM10 in five of the most polluted areas in the Republic of Serbia (Subotica, Smederevo, Bor, Valjevo, and Kraljevo). Non-carcinogenic (HQ and HI) and carcinogenic risk (CR) were calculated using USEPA methodology. Our results show that PM10 concentrations exceeded the annual limit of 40 μg/m3 at four out of five monitoring sites (ranging from 44.33 to 63.25 μg/m3). Results obtained from Bor monitoring station show that safe limits were exceeded for both children and adults, indicating an unacceptable risk (> 1) obtained for inhalation exposure to the As (HQ = 6.14) and Cd (HQ = 1.17), while total HI was 7.43, which characterized the risk as unacceptable. For the same station, the CR value was 1.44E−04 (> 1 × 10−4). In other sites, the risks were acceptable. The characterized risk from exposure to the toxic elements via PM10 in critical locations in Serbia contributes to improving air quality by requiring regulatory organs to take new actions and adopt new measures to reduce air pollution.
... This risk-risk approach monetises human life as to make regulatory comparisons possible. 4 Considering safety at work: working at height, which is mostly done by young personnel cause per victim a higher loss of DALY than occupational risks which cause primarily death and disability at a higher age, such as assumed nearness to chemicals that might be carcinogenic. The benefits of preventing falling accidents, which, again, are primarily focussed on younger employees, grosso modo is greater than diseases like cancer resulting from low-dose exposure to chemicals such as carcinogens. ...
Article
Full-text available
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. Less educated people are statistically likely to enjoy ten additional healthy years, if employed. Although there is no debate about the risks of exposure to high doses of chemicals, there is most certainly debate on the magnitude, nature and possible cumulative effects of low-dose exposure to chemicals. These are established by model-based assumptions. The current advisory structure in which the Health Council of the Netherlands restricts its focus to the immediate health benefits for workers on the basis of risk avoidance models, and the Social and Economic Council of the Netherlands which focuses primarily on policy costs for trade and industry, is hardly a sound basis for well-considered decision making. The challenge for the scientific experts is to provide political administrators with an insightful social cost-benefit analysis, including all the concomitant uncertainties.
Article
This study investigated the hormetic responses of soil alkaline phosphatase (ALP) to exogenous Cd under five different vegetation cover types in a typical coastal wetland, including mudflat (Mud), Phragmites australis (PA), Spartina alterniflora (SA), Metasequoia glyptostroboides (MG), and Cinnamomum camphora (CC). The results showed that the activity of soil ALP was significantly enhanced by exogenous 0.3–1.0, 0.2–0.8, 0.05–0.3, 0.05–0.6, and 0.05–0.60 mg Cd /kg in Mud, PA, SA, MG, and CC, respectively. Moreover, the Horzone (an integrated indicator of the stimulation phase) of Mud and PA was significantly higher than that of SA, MG, and CC. Multiple factor analysis revealed that soil chemical properties and soil bacteria community play an important role in the hormetic effect of soil ALP to Cd stress. Soil electric conductivity (EC) and the relative abundance of Gammaproteobacteria were also identified as key drivers of the hormetic effects of Cd on soil ALP under five vegetation cover types. These findings suggest that the soil ecosystem had better resistance to exogenous Cd stress under mudflat and native species (PA) than invasive species (SA), and artificial forests (MG and CC) when soil ALP activity was the test endpoint. Consequently, this study is beneficial for future ecological risk assessment of soil Cd contamination under divergent vegetation covers.
Article
Chemical reaction active sites of chloramphenicol are investigated by density functional theory. Three atomic sites are considered the most possible nucleophilic sites. Results indicate that the chemical reaction active sites are formed around four bond sites associated with three nucleophilic atom sites. CAP is a case of joint electrostatic and electron transfer control, and N5 is the most favourable site with electrostatic control, while the reaction between CAP and free radical is transfer control. Moreover, a detailed explanation on why bond (C1-C2) is considered the reactivity center of CAP and why no N-related products are generated in experiments is provided.
Article
This SI brought together scientists working in different research areas of environmental science and ecology in a call to honor Tony Stebbing, the father of environmental hormesis, the man who established the foundational basis of the field in a period of time when hormesis was even ridiculed. This collection of nearly 40 papers provides support to some of the now nearly 50-year-old hypotheses and expectations of Stebbing, including the general occurrence of hormesis across organisms and stressors. These studies also support his view that the stimulation occurs in the context of an adaptive response, which eventually protects organisms against toxic inhibition and helps them to overcome toxicity. However, this VSI served one more purpose. By bringing together people from multi-disciplinary fields, we hope to break the ice and bridge the gap among disciplines for trans-disciplinary research on environmental hormesis, as Stebbing had wished.
Article
Full-text available
Background and Objectives:Occupational exposure to metalworking fluid mist causes respiratory irritation. This study aimed to assess the relative risk of irritating effects in occupational exposure to metalworking fluids of lathe process.Materials and Methods: Sixty-five subjectsexposed to oil mist as exposed group and 65 administrative staff of the same industry as control group were selected. Health and Safety Executive/Health and Safety Laboratory (HSE/HSL) questionnaire was used for irritating effects. The US National Institutes of Health and Safety (NIOSH) method 5026 was used to monitoring respiratory exposure to oil mist. We also calculated the relative risk of irritating symptoms using MedCalc software.Thestudy was approvedby the ethics committee andconducted with the consent ofparticipants.Results:The mean time-weighted exposure to mineral oil mist in lathe workers was 7.10±3.49 mg/m3. The amount of throat irritation in machinists was significantly higher than the control group (p-value = 0.044).The relativerisk of irritating effects in the eyes, nose, mouth and throat in machinists is slightly higher than control subjects (p-value = 0.05).Conclusion:In this study, the occupational exposure in 67% of lathe workers is higher thanrecommended exposurelimitin Iran. Subjects by oil mists exposure represented a risk of irritating effects in the respiratory tract, especially the throat. For this reason, continuous assessment and control of exposure is are needed to reduce the risk of chronic diseases.
Article
Full-text available
Background and Objectives: Occupational exposure to metalworking fluid mist causes respiratory irritation. This study aimed to assess the relative risk of irritating effects in occupational exposure to metalworking fluids of lathe process. Materials and Methods: Sixty-five subjects exposed to oil mist as exposed group and 65 administrative staff of the same industry as control group were selected. Health and Safety Executive/Health and Safety Laboratory (HSE/HSL) questionnaire was used for irritating effects. The US National Institutes of Health and Safety (NIOSH) method 5026 was used to monitoring respiratory exposure to oil mist. We also calculated the relative risk of irritating symptoms using MedCalc software. The study was approved by the ethics committee and conducted with the consent of participants. Results: The mean time-weighted exposure to mineral oil mist in lathe workers was 7.10±3.49 mg/m3. The amount of throat irritation in machinists was significantly higher than the control group (p-value = 0.044).The relative risk of irritating effects in the eyes, nose, mouth and throat in machinists is slightly higher than control subjects (p-value = 0.05). Conclusion: In this study, the occupational exposure in 67% of lathe workers is higher than recommended exposure limit in Iran. Subjects by oil mists exposure represented a risk of irritating effects in the respiratory tract, especially the throat. For this reason, continuous assessment and control of exposure is are needed to reduce the risk of chronic diseases.
Chapter
Full-text available
Setting scientific and policy standards that benchmark the risks and benefits of products intended for human consumption is of great consequence for industry, policymakers, and consumers. The safety of food products consumed is more often than not defined as chemical product safety, meaning that the food product is regarded as “safe” when man-made chemicals such as antibiotics and/or pesticides are absent or only present at very low levels. Food safety is usually defined as such.
Article
Full-text available
A reproducibility crisis is a situation where many scientific studies cannot be reproduced. Inappropriate practices of science, such as HARKing, p-hacking, and selective reporting of positive results, have been suggested as causes of irreproducibility. In this editorial, I propose that a lack of raw data or data fabrication is another possible cause of irreproducibility. As an Editor-in-Chief of Molecular Brain , I have handled 180 manuscripts since early 2017 and have made 41 editorial decisions categorized as “Revise before review,” requesting that the authors provide raw data. Surprisingly, among those 41 manuscripts, 21 were withdrawn without providing raw data, indicating that requiring raw data drove away more than half of the manuscripts. I rejected 19 out of the remaining 20 manuscripts because of insufficient raw data. Thus, more than 97% of the 41 manuscripts did not present the raw data supporting their results when requested by an editor, suggesting a possibility that the raw data did not exist from the beginning, at least in some portions of these cases. Considering that any scientific study should be based on raw data, and that data storage space should no longer be a challenge, journals, in principle, should try to have their authors publicize raw data in a public database or journal site upon the publication of the paper to increase reproducibility of the published results and to increase public trust in science.
Article
Full-text available
1) Background: Emerging interest of physicians to use adipose-derived stem cells (ADSCs) for regenerative therapies and the fact that low-dose irradiation (LD-IR ≤ 0.1 Gy) has been reported to enhance the proliferation of several human normal and bone-marrow stem cells, but not that of tumor cells, lead to the idea of improving stem cell therapies via low-dose radiation. Therefore, the aim of this study was to investigate unwanted side effects, as well as proliferation-stimulating mechanisms of LD-IR on ADSCs. (2) Methods: To avoid donor specific effects, ADSCs isolated from mamma reductions of 10 donors were pooled and used for the radiobiological analysis. The clonogenic survival assay was used to classify the long-term effects of low-dose radiation in ADSCs. Afterwards, cytotoxicity and genotoxicity, as well as the effect of irradiation on proliferation of ADSCs were investigated. (3) Results: LD (≤ 0.1 Gy) of ionizing radiation promoted the proliferation and survival of ADSCs. Within this dose range neither geno-nor cytotoxic effects were detectable. In contrast, greater doses within the dose range of >0.1-2.0 Gy induced residual double-strand breaks and reduced the long-term survival, as well as the proliferation rate of ADSCs. (4) Conclusions: Our data suggest that ADSCs are resistant to LD-IR. Furthermore, LD-IR could be a possible mediator to improve approaches of stem cells in the field of regenerative medicine.
Article
Full-text available
Valentin Amrhein, Sander Greenland, Blake McShane and more than 800 signatories call for an end to hyped claims and the dismissal of possibly crucial effects.
Article
Full-text available
The solutions adopted by the high-energy physics community to foster reproducible research are examples of best practices that could be embraced more widely. This first experience suggests that reproducibility requires going beyond openness.
Article
Full-text available
It is ethically mandated that potential beneficial aspects of low exposure to potentially hazardous material are incorporated in the risk-benefit balancing procedure. The potential harm done by pollutants does not justify the invocation of a categorical principle. Minimisation of risk is not required if health benefits are also at stake. Society needs to find an informed consent on the threshold of risk below compensation of goods is legitimate and morally justified. Such a threshold can be defined context-specific but any human action associated with potential health impacts makes such an acceptability judgment - implicitly or explicitly. Incorporating hormesis into risk management forces regulators to make such thresholds explicit. Once as risk is below this threshold all positive and negative impacts are subject to a relative balancing towards reaching a final judgment on acceptability and necessary risk management options. This balancing risk cannot be reduced to body counts: equity issues, context specific circumstances (voluntary or involuntary exposure, for example), avoidance of risks, the nature of vulnerable groups and many other factors need to be taken into account. Such a complex weighing exercise is best performed by an analytic-deliberative process by which the best available knowledge of impacts (including their uncertain ties) is fed into a deliberating body of individuals representing all sides of the debate. Organizing and structuring an analytic-deliberative discourse for assigning painful trade-offs goes beyond the good intention to have all relevant stakeholders involved in decision making.. Discursive processes need a structure that assures the integration of technical expertise, regulatory requirements, and public values. These different inputs should be combined in such a fashion that they contribute to the deliberation process the type of expertise and knowledge that can claim legitimacy within a rational decision making procedure.
Article
Full-text available
Improving the reliability and efficiency of scientific research will increase the credibility of the published scientific literature and accelerate discovery. Here we argue for the adoption of measures to optimize key elements of the scientific process: methods, reporting and dissemination, reproducibility, evaluation and incentives. There is some evidence from both simulations and empirical studies supporting the likely effectiveness of these measures, but their broad adoption by researchers, institutions, funders and journals will require iterative evaluation and improvement. We discuss the goals of these measures, and how they can be implemented, in the hope that this will facilitate action toward improving the transparency, reproducibility and efficiency of scientific research.
Article
Full-text available
Classification schemes for carcinogenicity based solely on hazard-identification such as the IARC monograph process and the UN system adopted in the EU have become outmoded. They are based on a concept developed in the 1970s that chemicals could be divided into two classes: carcinogens and non-carcinogens. Categorization in this way places into the same category chemicals and agents with widely differing potencies and modes of action. This is how eating processed meat can fall into the same category as sulfur mustard gas. Approaches based on hazard and risk characterization present an integrated and balanced picture of hazard, dose response and exposure and allow informed risk management decisions to be taken. Because a risk-based decision framework fully considers hazard in the context of dose, potency, and exposure the unintended downsides of a hazard only approach are avoided, e.g., health scares, unnecessary economic costs, loss of beneficial products, adoption of strategies with greater health costs, and the diversion of public funds into unnecessary research. An initiative to agree upon a standardized, internationally acceptable methodology for carcinogen assessment is needed now. The approach should incorporate principles and concepts of existing international consensus-based frameworks including the WHO IPCS mode of action framework.
Article
The assumption that chemical and radiation induced cancers act in a manner that is additive to background was proposed in the mid-1970s. It was adopted by the U.S. Environmental Protection Agency (EPA) in 1986 and then subsequently by other regulatory agencies worldwide for cancer risk assessment. It ensured that cancer risks at low doses act in a linear fashion. The additive to background process assumes that the mechanism(s) resulting in induced (i.e., treatment related) and spontaneous (i.e., control group) cancers are identical. This assumption could not be properly evaluated due to inadequate mechanistic data when it was proposed in the 1970s. Using the findings of modern molecular toxicology, including oncogene activation/mutation, gene regulation, and molecular pathway analyses, the additive to background assumption was evaluated in the present paper. Based on published studies with 45 carcinogens over 13 diverse mammalian models and for a broad range of tumor types compelling evidence indicates that carcinogen-induced tumors are mediated in general via mechanisms that are not identical to those affecting the occurrence of the same type of spontaneous tumors in appropriate control groups. These findings, which challenge a fundamental assumption of the additive to background concept, have significant implications for cancer risk assessment policy, regulatory agency practices, as well as fundamental concepts of cancer biology.
Article
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., the linear no-threshold (LNT) and hormetic dose-response models. The integration would yield the optimized response at a risk of 10 with the LNT model. The integrative functionality of the LNT and hormetic dose response models provides an improved estimation of tumor incidence through model uncertainty analysis and major reductions in cancer incidence via hormetic model estimates. This novel approach to cancer risk assessment offers significant improvements over current risk assessment approaches by revealing a regulatory sweet spot that maximizes public health benefits while incorporating practical approaches for model validation.