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Abstract The health of honey bee queens is crucial for colony success, particularly during stressful periods like overwintering. To accompany a previous longitudinal study of colony and worker health, we explored niche-specific gut microbiota, host gene expression, and pathogen prevalence in honey bee queens overwintering in a warm southern climate. We found differential gene expression and bacterial abundance with respect to various pathogens throughout the season. Biologically older queens had larger microbiotas, particularly enriched in Bombella and Bifidobacterium. Both Deformed Wing Virus A and B subtypes were highest in the fat body tissue in January, correlating with colony Varroa levels, and Deformed Wing Virus titers in workers. High viral titers in queens were associated with decreased vitellogenin expression, suggesting a potential trade-off between immune function and reproductive capacity. Additionally, we found a complex and dynamic relationship between these viral loads and immune gene expression, indicating a possible breakdown in the coordinated immune response as the season progressed. Our study also revealed a potential link between Nosema and Melissococcus plutonius infections in queens, demonstrating that seasonal opportunism is not confined to just workers. Overall, our findings highlight the intricate interplay between pathogens, metabolic state, and immune response in honey bee queens. Combined with worker and colony-level metrics from the same colonies, our findings illustrate the social aspect of queen health and resilience over the winter dearth.

Abstract Probiotics are widely used in agriculture including commercial beekeeping, but there is little evidence supporting their effectiveness. Antibiotic treatments can greatly distort the gut microbiome, reducing its protective abilities and facilitating the growth of antibiotic resistant pathogens. Commercial beekeepers regularly apply antibiotics to combat bacterial infections, often followed by an application of non-native probiotics advertised to ease the impact of antibiotic-induced gut dysbiosis. We tested whether probiotics affect the gut microbiome or disease prevalence, or rescue the negative effects of antibiotic induced gut dysbiosis. We found no difference in the gut microbiome or disease markers by probiotic application or antibiotic recovery associated with probiotic treatment. A colony-level application of the antibiotics oxytetracycline and tylosin produced an immediate decrease in gut microbiome size, and over the longer-term, very different and persistent dysbiotic effects on the composition and membership of the hindgut microbiome. Our results demonstrate the lack of probiotic effect or antibiotic rescue, detail the duration and character of dysbiotic states resulting from different antibiotics, and highlight the importance of the gut microbiome for honeybee health.

We present a comprehensive overview of changes in thyroxine (T4) and thyroid stimulating hormone (TSH) serum concentrations after pre-gestational, gestational and/or lactation exposures of rodents to various chemicals that affect the thyroid hormone system. We show that T4 and TSH changes consistent with the idealized view of the hypothalamic-pituitary-thyroid (HPT) feedback loop (T4 decrements accompanied by TSH increases) are observed with only a relatively small set of chemicals. Most substances affect concentrations of various thyroid hormones without increasing TSH. Studies of altered T4 concentrations after gestational exposures are limited to a relatively small set of chemicals in which pesticides, pharmaceuticals and industrial chemicals are under-represented. Our risk-of-bias analysis exposed deficits in T4/TSH analytics as a problem area. By relating patterns of T4 – TSH changes to mode-of-action (MOA) information, we found that chemicals capable of disrupting the HPT feedback frequently affected thyroid hormone synthesis, while substances that produced T4 serum decrements without accompanying TSH increases lacked this ability, but often induced liver enzyme systems responsible for the elimination of TH by glucuronidation. Importantly, a multitude of MOA leads to decrements of serum T4. The current EU approaches for identifying thyroid hormone system-disrupting chemicals, with their reliance on altered TH serum levels as indicators of a hormonal mode of action and thyroid histopathological changes as indicators of adversity, will miss chemicals that produce T4/T3 serum decreases without accompanying TSH increases. This is of concern as it may lead to a disregard for chemicals that produce developmental neurotoxicity by disrupting adequate T4/T3 supply to the brain, but without increasing TSH.

Background: Human chorionic gonadotropin (hCG) is produced by the placenta and plays an essential role in the maintenance of pregnancy. Endocrine disrupting chemicals (EDCs) have the potential to interfere with functions related to the production and secretion of hCG; however associations between exposure to EDCs and hCG concentrations in humans remain to be elucidated. Objectives: To investigate the association of urinary, serum and plasma concentrations of EDCs during pregnancy with serum hCG concentrations. Methods: We utilized data form the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) study. We investigated the association of 26 EDCs measured in early pregnancy urine or blood with serum hCG concentrations using multi-variable adjusted linear regression models per EDC and Weighted Quantile Sum (WQS) regression with repeated holdout validation for the EDCs mixture. Results: In 2,039 included women, higher exposure to bisphenol A was associated with lower hCG (beta [95% CI]: −0.06 [−0.11 to −0.002]) while higher triclosan exposure was associated with a higher hCG (0.02 [0.003 to 0.04]). Higher exposure to several phthalates, including mono-ethyl and mono-butyl phthalates (MEP and MBP) as well as metabolites of di-2-ethylhexyl phthalate (DEHP) was associated with a lower hCG (beta [95% CI] for sum of DEHP metabolites: −0.13 [−0.19 to −0.07]). Likewise, higher exposure to several polychlorinated biphenyls (PCBs) was associated with a lower hCG. In the WQS regression, each quartile increase in the EDCs mixture was associated with −0.27 lower hCG (95% CI: −0.34 to −0.19). Discussion: Higher exposure to several EDCs during pregnancy was associated with a lower hCG; and despite the small effect sizes, still indicating that the exposure may negatively affect production or secretion of hCG by the placenta. Our results provide the impetus for future experimental studies to investigate the placenta as a target organ for adverse effects of EDCs.

Endocrine-disrupting chemicals (EDCs) are exogenous chemicals that interfere with hormone action, thereby increasing the risk of adverse health outcomes, including cancer, reproductive impairment, cognitive deficits and obesity. A complex literature of mechanistic studies provides evidence on the hazards of EDC exposure, yet there is no widely accepted systematic method to integrate these data to help identify EDC hazards. Inspired by work to improve hazard identification of carcinogens using key characteristics (KCs), we have developed ten KCs of EDCs based on our knowledge of hormone actions and EDC effects. In this Expert Consensus Statement, we describe the logic by which these KCs are identified and the assays that could be used to assess several of these KCs. We reflect on how these ten KCs can be used to identify, organize and utilize mechanistic data when evaluating chemicals as EDCs, and we use diethylstilbestrol, bisphenol A and perchlorate as examples to illustrate this approach.

Abstract Background Mixture risk assessments require reference doses for common health endpoints of all the chemicals to be considered together. In support of a mixture risk assessment for male reproductive health, we conducted a systematic review of the literature on associations between exposures to Polychlorinated Biphenyls (PCBs) and declines in semen quality. PCBs can act as Aryl-hydrocarbon Receptor (AhR)-agonists and Androgen Receptor (AR)-antagonists, both mechanisms which can affect sperm parameters. PCBs and other AR-antagonists can produce additive combination effects. Based on these observations our objective was to systematically gather data from animal and human studies to derive a reference dose for declines in semen quality for individual PCB. Methods We systematically reviewed and evaluated the evidence in human epidemiological and experimental animal studies on associations between PCBs and deteriorations in semen quality. Human data and findings from animal studies with PCB mixtures were considered as supporting evidence. Information for individual congeners from animal studies was required for inclusion in mixture risk assessment. Using a robust confidence rating approach, we identified suitable studies to derive reference doses for individual PCB congeners. Results Evaluation of human epidemiological studies revealed several reports of adverse effects on sperm parameters linked to PCB exposures, although some studies reported improved semen quality. Our review of experimental animal studies found that treatments with PCBs affected semen quality, in most cases adversely. We found robust evidence that PCB-118 and -169 were linked to declines in semen quality. Evidence for adverse effects of PCB-126, -132, -149, and -153 was moderate, whereas for PCB-77 it was slight and for PCB-180 indeterminate. Using widely accepted risk assessment procedures, we estimated reference dose values of 0.0029 µg/kg/day for PCB-118 and 0.00533 µg/kg/day for PCB-169. In addition, we derived values for PCB-126: 0.000073 µg/kg/day, PCB-132: 0.0228 µg/kg/day, PCB-149: 0.656 µg/kg/day, and PCB-153: 0.0058 µg/kg/day. Conclusions We found robust evidence for links between PCB exposure and deteriorations in semen quality, and derived reference doses for a set of congeners. We intend to use these values in combination with congener-specific exposure data in a mixture risk assessment for declines in semen quality, involving several other antiandrogenic chemicals.

Abstract To support a mixture risk assessment with a focus on developmental neurotoxicity we evaluated the strength of evidence for associations of cadmium exposures with declines in IQ by conducting a systematic review and confidence rating. We searched peer-reviewed studies published in English between 2012 and July 2021 and identified 15 eligible studies (11 prospective cohort studies, and 4 cross-sectional studies). Of the 10 studies that observed associations of cadmium exposure with child IQ declines, two achieved an overall “High (H)” confidence rating, five a “Medium to High (M/H)”, one a “Medium (M)” and two a “Low (L)” confidence rating. Five studies did not detect significant associations between cadmium exposure and reduced cognitive ability; of these, two received a “High (H)” confidence rating, two an overall rating of “Medium to High (M/H)” and one a “Medium (M)” rating. The null findings reported by the “High (H)” and Medium to High (M/H)” studies could partly be explained by low exposures to cadmium or confounding with high levels of lead. By using a one-compartment toxicokinetic model in a reverse dosimetry approach, we estimated that a daily intake of 0.2 μg/kg body weight/day corresponds to urinary cadmium levels no longer associated with cognitive declines observed in a “High (H)”-confidence study. This estimate is 1.8-fold lower than the current health-based guidance value (HBGV) for kidney toxicity of 0.36 μg/kg bodyweight/day established by the European Food Safety Authority (EFSA). Our value does not have the normative character associated with health-based guidance values and is intended only as a reasonable estimate for the purpose of mixture risk assessments. However, with cadmium exposures in Europe between 0.28 (middle bound) and up to 0.52 μg/kg bodyweight/day (95th percentile), our review suggests that pregnant women and children are poorly protected against neurodevelopmental effects. This warrants a revision of the current HBGV.

Flame retardants are chemical substances that are intended to mitigate fire safety risks posed by a range of goods including furniture, electronics, and building insulation. There are growing concerns about their effectiveness in ensuring fire safety and the potential harms they pose to human health and the environment. In response to these concerns, on 13 June 2022, a roundtable of experts was convened by the UKRI Six Clean Air Strategic Priorities Fund programme 7. The meeting produced a Consensus Statement that summarises the issues around the use of flame retardants, laying out a series of policy recommendations that should lead to more effective fire safety measures and reduce the human and environmental health risks posed by these potentially toxic chemicals.

Objectives: To investigate the association of exposure to per- and polyfluoroalkyl substances (PFAS) during early pregnancy with markers of the maternal thyroid system. Methods: Serum concentrations of seven PFAS as well as thyroid stimulating hormone (TSH), free and total thyroxine (FT4 and TT4), free and total triiodothyronine (FT3 and TT3) were measured in pregnant women in early pregnancy in the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) study. Outcomes were concentrations of TSH and thyroid hormones, FT4/FT3 or TT4/TT3 ratios, TSH/FT4 ratio as a marker of the negative feedback loop, TT4/FT4 or TT3/FT3 ratios as markers of the binding of thyroid hormones to binding proteins. Results: The study population comprised 2,008 women with median (95% range) gestational age of 10 (6–14) weeks. There was no association between PFAS and TSH. Higher PFNA, PFDA, PFHpA and PFOA levels were associated with a higher FT4 (largest effect estimate for PFDA: β [95% CI]: 0.27 [0.10 to 0.45], P = 0.002). Higher PFUnDA levels, but no other PFAS, were associated with a lower FT3 (β [95% CI]: −0.05 [-0.09 to −0.01], P = 0.005). Higher PFUnDA levels were associated with lower TT4 (β [95% CI]: −1.58 [-3.07 to −0.09]) and there was an inverted U-shaped association of PFOS with TT4 (P = 0.03). Higher PFDA, PFUnDA, PFHpA levels were associated with a lower TT3. Overall, higher PFAS concentrations were associated with a higher FT4/FT3 ratio and a higher TT4/TT3 ratio. There was no association of PFAS with the TSH/FT4 ratio. Higher concentrations of several PFAS were associated with lower TT4/FT4 and TT3/FT3 ratios. Conclusions: These findings translate results from experimental studies suggesting that exposure to PFAS may interfere with the thyroid system during pregnancy. Further experimental studies should take into account human evidence to better understand the potential underlying mechanisms of thyroid disruption by PFAS exposure.

Background: Semen quality in men continues to decline in Western countries, but the contours of the issue remain obscure, in relation to contributing chemicals. Objectives: To obtain more clarity about the chemicals that drive the deterioration of semen quality, we conducted a mixture risk assessment based on European exposures. Methods: We included chemicals capable of affecting semen quality after prenatal exposures, among them androgen receptor antagonists, substances that disrupt prostaglandin signalling, suppress testosterone synthesis, inhibit steroidogenic enzymes or activate the aryl hydrocarbon receptor. We employed the Hazard Index approach (HI), based on risk quotients of exposures in Europe and reference doses for reductions in semen quality. By summing up the risk quotients of the 29 chemicals included in the assessment we examined fold-exceedances of “acceptable” mixture exposures relative to an index value of 1. For bisphenols A, F, S, phthalates DEHP, DnBP, BBzP, DiNP, n-butyl paraben and paracetamol we relied on biomonitoring studies in which these 9 chemicals were measured together in the same subjects. This allowed us to construct personalised Hazard Indices. Results: Highly exposed subjects experienced combined exposures to the 9 chemicals that exceeded the index value of 1 by more than 100-fold; the median was a 17-fold exceedance. Accounting for median background exposures to the remaining 20 chemicals added a Hazard Index of 1.39. Bisphenol A made the largest contribution to the HI, followed by polychlorinated dioxins, bisphenols S and F and DEHP. Eliminating bisphenol A alone would still leave unacceptably high mixture risks. Paracetamol is also a driver of mixture risks among subjects using the drug. Conclusions: Tolerable exposures to substances associated with deteriorations of semen quality are exceeded by a large margin. Bisphenols, polychlorinated dioxins, phthalates and analgesics drive these risks. Dedicated efforts towards lowering exposures to these substances are necessary to mitigate risks.

BackgroundAfrica faces a number of unique environmental challenges. Unfortunately, it lacks the infrastructure needed to support the comprehensive environmental studies that could provide the scientific basis to inform environmental policies. There are a number of known sources of endocrine-disrupting chemicals (EDCs) and other hazardous chemicals in Africa. However, a coordinated approach to identify and monitor these contaminants and to develop strategies for public health interventions has not yet been made.ObjectivesThis commentary summarizes the scientific evidence presented by experts at the First African Endocrine Disruptors meeting. We describe a "call to action" to utilize the available scientific knowledge to address the impact of EDCs on human and wildlife health in Africa.DiscussionWe identify existing knowledge gaps about exposures to EDCs in Africa and describe how well-designed research strategies are needed to address these gaps. A lack of resources for research and a lag in policy implementation slows down intervention strategies and poses a challenge to advancing future health in Africa.ConclusionTo address the many challenges posed by EDCs, we argue that Africans should take the lead in prioritization and evaluation of environmental hazards, including EDCs. We recommend the institution of education and training programs for chemical users, adoption of the precautionary principle, establishment of biomonitoring programs, and funding of community-based epidemiology and wildlife research programs led and funded by African institutes and private companies. https://doi.org/10.1289/EHP1774.

BackgroundThe issue of endocrine disrupting chemicals (EDCs) is receiving wide attention from both the scientific and regulatory communities. Recent analyses of the EDC literature have been criticized for failing to use transparent and objective approaches to draw conclusions about the strength of evidence linking EDC exposures to adverse health or environmental outcomes. Systematic review methodologies are ideal for addressing this issue as they provide transparent and consistent approaches to study selection and evaluation. Objective methods are needed for integrating the multiple streams of evidence (epidemiology, wildlife, laboratory animal, in vitro, and in silico data) that are relevant in assessing EDCs.MethodsWe have developed a framework for the systematic review and integrated assessment (SYRINA) of EDC studies. The framework was designed for use with the International Program on Chemical Safety (IPCS) and World Health Organization (WHO) definition of an EDC, which requires appraisal of evidence regarding 1) association between exposure and an adverse effect, 2) association between exposure and endocrine disrupting activity, and 3) a plausible link between the adverse effect and the endocrine disrupting activity.ResultsBuilding from existing methodologies for evaluating and synthesizing evidence, the SYRINA framework includes seven steps: 1) Formulate the problem; 2) Develop the review protocol; 3) Identify relevant evidence; 4) Evaluate evidence from individual studies; 5) Summarize and evaluate each stream of evidence; 6) Integrate evidence across all streams; 7) Draw conclusions, make recommendations, and evaluate uncertainties. The proposed method is tailored to the IPCS/WHO definition of an EDC but offers flexibility for use in the context of other definitions of EDCs.ConclusionsWhen using the SYRINA framework, the overall objective is to provide the evidence base needed to support decision making, including any action to avoid/minimise potential adverse effects of exposures. This framework allows for the evaluation and synthesis of evidence from multiple evidence streams. Finally, a decision regarding regulatory action is not only dependent on the strength of evidence, but also the consequences of action/inaction, e.g. limited or weak evidence may be sufficient to justify action if consequences are serious or irreversible.

Background: In STEM-innovation implementation processes, PD curriculum materials are designed to support facilitators in conducting professional development. However, little is known about the facilitators' practices in adapting PD materials. This study transfers frameworks from teachers' curriculum adaptation to facilitators and qualitatively investigates adaptation practices of 11 expert facilitators and their underlying individual perspectives in group discussion and interviews. In the study, a framework was developed for capturing facilitators' adaptation practices. Results: The qualitative analysis shows that all so-called materialized adaptation actions (follow, omit, modify, sort, and create) are conducted on different grain sizes of PD material chunks and with various underlying perspectives. Additionally, thematic adaptation actions mainly refer to facilitators' ways of dealing with examples and theoretical constructs. Dealing with examples often involves shifts in forms of knowledge, e.g., when facilitators situate a theoretical construct in concrete classroom practices. The article contributes to theory generation on facilitators' adaptation practices, especially by introducing and illuminating the distinction between materialized and thematic adaptation actions. Conclusion: The empirical insights of various underlying perspectives call for practical consequences for the design of PD curriculum material: To ensure that adaptation practices retain or improve quality, the structure of PD curriculum material must preserve the minimal adequate grain size (better the thematic block than the single slide) and the need for shifts in the forms of addressed knowledge.

This article describes Ulrich Kortenkamp's Place Value Chart app and the accompanying teacher guide developed by the members of an international research team led by regular contributor Kevin Larkin.

A previous report documented that endocrine disrupting chemicals contribute substantially to certain forms of disease and disability. In the present analysis, our main objective was to update a range of health and economic costs that can be reasonably attributed to endocrine disrupting chemical exposures in the European Union, leveraging new burden and disease cost estimates of female reproductive conditions from accompanying report. Expert panels evaluated the epidemiologic evidence, using adapted criteria from the WHO Grading of Recommendations Assessment, Development and Evaluation Working Group, and evaluated laboratory and animal evidence of endocrine disruption using definitions recently promulgated by the Danish Environmental Protection Agency. The Delphi method was used to make decisions on the strength of the data. Expert panels consensus was achieved for probable (>20%) endocrine disrupting chemical causation for IQ loss and associated intellectual disability; autism; attention deficit hyperactivity disorder; endometriosis; fibroids; childhood obesity; adult obesity; adult diabetes; cryptorchidism; male infertility, and mortality associated with reduced testosterone. Accounting for probability of causation, and using the midpoint of each range for probability of causation, Monte Carlo simulations produced a median annual cost of €163 billion (1.28% of EU Gross Domestic Product) across 1000 simulations. We conclude that endocrine disrupting chemical exposures in the EU are likely to contribute substantially to disease and dysfunction across the life course with costs in the hundreds of billions of Euros per year. These estimates represent only those endocrine disrupting chemicals with the highest probability of causation; a broader analysis would have produced greater estimates of burden of disease and costs.

We present a detailed response to the critique of "State of the Science of Endocrine Disrupting Chemicals 2012" (UNEP/WHO, 2013) by financial stakeholders, authored by Lamb et al. (2014). Lamb et al.'s claim that UNEP/WHO (2013) does not provide a balanced perspective on endocrine disruption is based on incomplete and misleading quoting of the report through omission of qualifying statements and inaccurate description of study objectives, results and conclusions. Lamb et al. define extremely narrow standards for synthesizing evidence which are then used to dismiss the UNEP/WHO 2013 report as flawed. We show that Lamb et al. misuse conceptual frameworks for assessing causality, especially the Bradford-Hill criteria, by ignoring the fundamental problems that exist with inferring causality from empirical observations. We conclude that Lamb et al.'s attempt of deconstructing the UNEP/WHO (2013) report is not particularly erudite and that their critique is not intended to be convincing to the scientific community, but to confuse the scientific data. Consequently, it promotes misinterpretation of the UNEP/WHO (2013) report by non-specialists, bureaucrats, politicians and other decision makers not intimately familiar with the topic of endocrine disruption and therefore susceptible to false generalizations of bias and subjectivity.

Background: The extent of thyroid disruptive effects of phthalates during pregnancy remains unclear. Aim: To investigate the association of maternal urinary phthalates with markers of the thyroid system during early pregnancy. Methods: Urinary concentrations of phthalate metabolites and serum concentrations of thyroid stimulating hormone (TSH), free and total thyroxine (FT4 and TT4) and free and total triiodothyronine (FT3 and TT3) were measured in pregnant women in early pregnancy in the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy study (2007-ongoing), a population-based prospective cohort. Results: In the 1,996 included women, higher di-ethyl-hexyl phthalate (DEHP) metabolites were associated with a lower FT4 (β [SE] for the molar sum: −0.13 [0.06], P = 0.03) and a higher TSH/FT4 ratio (0.003 [0.001], P = 0.03). Higher concentrations of di-iso-nonyl phthalate (DINP) metabolites were associated with a lower TT4 (β [SE] for the molar sum: 0.93 [0.44], P = 0.03) as well as with lower TT4/FT4 and TT4/TT3 ratios. Higher metabolites of both dibutyl and butyl-benzyl phthalate (DBP and BBzP) were associated with lower T4/T3 ratio (free and total) and higher FT4/TT4 and FT3/TT3 ratios. A higher diisononyl cyclohexane dicarboxylate (DINCH) metabolite concentration was associated with a higher TT3. Conclusions: These results translate results from experimental studies suggesting that exposure to phthalates may interfere with the thyroid system during pregnancy. This is also true for compounds that have been introduced to replace known disruptive phthalates. Further experimental studies should take into account the human evidence to better investigate the potential underlying mechanisms of thyroid disruption by phthalates.

In this article we describe long-standing user interface issues with Dynamic Geometry Software and common approaches to address them. We describe first prototypes of multi-touch-capable DGS. We also give some hints on the educational benefits of proper user interface design.

In this article we demonstrate how the combination of a system for dynamic geometry with a freely programmable scripting environment can be advantageously used in teaching and research. We explain the reasons behind various design decisions that were made by us when designing the language "CindyScript" and give examples that proof how they lead to easy and understandable code that can be used in education. We give several concrete application scenarios of the language that was developed by the authors and seamlessly interacts with the dynamic geometry system Cinderella.

The three-space theory of problem solving predicts that thequality of a learner’s model and the goal specificity of a taskinteract on knowledge acquisition: Learners having a goodmodel should learn more with a nonspecific than a specificgoal, which should not apply to learners having a poor model.This study tested this prediction using a computer basedlearning task on torques. Participants (N = 77 psychologystudents) either had to test hypotheses with a simulation of alever system (nonspecific goal), or to produce given valuesfor variables in this simulation (specific goal). In the goodmodel condition but not in the poor model condition they sawthe torque depicted as an area. Results revealed the predictedinteraction. A nonspecific goal only resulted in better learningwhen a good model of torques was provided but not with apoor model. Our findings support the three-space theory.They emphasize the importance of understanding in studyingproblem solving and stress the need to study underlyingprocesses.

Hexavalent chromium (Cr(VI)), nickel (Ni) and polycyclic aromatic hydrocarbons (PAHs) are genotoxic co-occurring lung carcinogens whose occupational health risk is still understudied. This study, conducted within the European Human Biomonitoring Initiative (HBM4EU), aimed at performing a mixtures risk assessment (MRA) based on published human biomonitoring (HBM) data from Cr(VI), Ni and/or PAHs occupational co-exposure in Europe. After data extraction, Risk Quotient (RQ) and Sum of Risk Quotients (SRQ) were calculated for binary and ternary mixtures to characterise the risk. Most selected articles measured urinary levels of Cr and Ni and a SRQ > 1 was obtained for co-exposure levels in welding activities, showing that there is concern regarding co-exposure to these substances. Similarly, co-exposure to mixtures of Cr(VI), Ni and PAHs in waste incineration settings resulted in SRQ > 1. In some studies, a low risk was estimated based on the single substances’ exposure level (RQ < 1), but the mixture was considered of concern (SRQ > 1), highlighting the relevance of considering exposure to the mixture rather than to its single components. Overall, this study points out the need of using a MRA based on HBM data as a more realistic approach to assess and manage the risk at the workplace, in order to protect workers’ health.

Distinguishing chemical mixtures in terms of the similarity vs. dissimilarity of their components' mechanisms or modes of action (MOAs) is perceived as a key issue in mixture risk assessment. However, [...]