Archives of Industrial Hygiene and Toxicology

Science-based evidence on pathways and effects of human exposure to micro- and nanoplastics

Nikolina Kalčec — 2024-03-12

Human exposure to plastic particles has raised great concern among all relevant stakeholders involved in the protection of human health due to the contamination of the food chain, surface waters, and even drinking water as well as due to their persistence and bioaccumulation. Now more than ever, it is critical that we understand the biological fate of plastics and their interaction with different biological systems. Because of the ubiquity of plastic materials in the environment and their toxic potential, it is imperative to gain reliable, regulatory-relevant, science-based data on the effects of plastic micro- and nanoparticles (PMNPs) on human health in order to implement reliable risk assessment and management strategies in the circular economy of plastics. This review presents current knowledge of human-relevant PMNP exposure doses, pathways, and toxic effects. It addresses difficulties in properly assessing plastic exposure and current knowledge gaps and proposes steps that can be taken to underpin health risk perception, assessment, and mitigation through rigorous science-based evidence. Based on the existing scientific data on PMNP adverse health effects, this review brings recommendations on the development of PMNP-specific adverse outcome pathways (AOPs) following the AOP Users' Handbook of the Organisation for Economic Co-operation and Development (OECD).

Polychlorinated biphenyls in mussels, small pelagic fish, tuna, turtles, and dolphins from the Croatian Adriatic Sea waters: an overview of the last two decades of monitoring

Snježana Herceg Romanić — 2024-03-11

This review summarises our two decades of polychlorinated biphenyl (PCB) monitoring in different marine organisms along the eastern Adriatic Sea. The aim was to gain an insight into the trends of PCB distribution in order to evaluate the effectiveness of past and current legislation and suggest further action. Here we mainly focus on PCB levels in wild and farmed Mediterranean mussels, wild and farmed bluefin tuna, loggerhead sea turtles, common bottlenose dolphins, and small pelagic fish. The use of artificial intelligence and advanced statistics enabled an insight into the influence of various variables on the uptake of PCBs in the investigated organisms as well as into their mutual dependence. Our findings suggest that PCBs in small pelagic fish and mussels reflect global pollution and that high levels in dolphins and wild tuna tissues raise particular concern, as they confirm their biomagnification up the food chain. Therefore, the ongoing PCB monitoring should focus on predatory species in particular to help us better understand PCB contamination in marine ecosystems in our efforts to protect the environment and human health.

Athlete biological passport: longitudinal biomarkers and statistics in the fight against doping

Dora Dragčević — 2024-02-28

As novel substances, short time windows, and limits of detection increasingly challenge direct methods of doping detection in sports, indirect tools inevitably take a greater role in the fight against it. One such tool is the athlete biological passport (ABP) – a longitudinal profiling of the measured haematological and biochemical biomarkers, combined with calculated scores, against the background of epidemiological data crucial for doping detection. In both of its modules, haematological and steroidal, ABP parameters are analysed with the Bayesian adaptive model, which individualises reference and cut-off values to improve its sensitivity. It takes into account the confounding factors with proven and potential influence on the biomarkers, such as race and altitude exposure. The ABP has already changed the fight against doping, but its importance will further grow with the new modules (e.g., endocrinological), parameters (e.g., plasma volume-independent parameters), and complementing indirect methods (e.g., transcriptomic).

Frequency of regular walking among Croatian adults

Slaven Krtalić — 2024-02-22

The aim of this study was to determine the share of Croatian adults who walk 210 min or more a week and to explore the relationship between regular walking and demographic factors, health-related behaviours, and chronic non-communicable diseases/conditions. To this end, we used the EHIS-PAQ questionnaire and collected self-reported data on minutes spent walking during a typical week from a total of 3,496 respondents. The data were additionally analysed by gender, age, education, residence (urban/rural), counties and regions, smoking, other types of physical activity, and diseases/chronic conditions. The results show that, overall, 40.9 % of the adult Croatian population walks 210 or more minutes a week, with the largest share found among those from the Lika-Senj County (76.8 %), those who spend 300 min or more weekly on health-enhancing (non-work-related) aerobic physical activity (57.6 %), those who reported having diabetes (49.3 %), and those aged 65–74 years (44.7 %). Despite its limitations, our study gives a valuable insight into the frequency and factors determining healthy walking habits in a representative sample of Croatian adults and provides grounds for further research.

Evaluation of the risk of occupational exposure to antineoplastic drugs in healthcare sector: part II – the application of the FMECA method to compare manual vs automated preparation

Stefano Dugheri — 2024-03-14

Healthcare workers handling antineoplastic drugs (ADs) in preparation units run the risk of occupational exposure to contaminated surfaces and associated mutagenic, teratogenic, and oncogenic effects of those drugs. To minimise this risk, automated compounding systems, mainly robots, have been replacing manual preparation of intravenous drugs for the last 20 years now, and their number is on the rise. To evaluate contamination risk and the quality of the working environment for healthcare workers preparing ADs, we applied the Failure Mode Effects and Criticality Analysis (FMECA) method to compare the acceptable risk level (ARL), based on the risk priority number (RPN) calculated from five identified failure modes, with the measured risk level (MRL). The model has shown higher risk of exposure with powdered ADs and containers not protected by external plastic shrink film, but we found no clear difference in contamination risk between manual and automated preparation. This approach could be useful to assess and prevent the risk of occupational exposure for healthcare workers coming from residual cytotoxic contamination both for current handling procedures and the newly designed ones. At the same time, contamination monitoring data can be used to keep track of the quality of working conditions by comparing the observed risk profiles with the proposed ARL. Our study has shown that automated preparation may have an upper hand in terms of safety but still leaves room for improvement, at least in our four hospitals.

Increased oxidative stress in shoe industry workers with low-level exposure to a mixture of volatile organic compounds

Nina Umićević — 2024-03-06

This study aimed to assess the redox status and trace metal levels in 49 shoe industry workers (11 men and 38 women) occupationally exposed to a mixture of volatile organic compounds (VOCs), which includes aliphatic hydrocarbons, aromatic hydrocarbons, ketones, esters, ethers, and carboxylic acids. All measured VOCs were below the permitted occupational exposure limits. The control group included 50 unexposed participants (25 men and 25 women). The following plasma parameters were analysed: superoxide anion (O₂^•-), advanced oxidation protein products (AOPP), total oxidative status (TOS), prooxidant-antioxidant balance (PAB), oxidative stress index (OSI), superoxide dismutase (SOD) and paraoxonase-1 (PON1) enzyme activity, total SH group content (SHG), and total antioxidant status (TAS). Trace metal levels (copper, zinc, iron, magnesium, and manganese) were analysed in whole blood. All oxidative stress and antioxidative defence parameters were higher in the exposed workers than controls, except for PON1 activity. Higher Fe, Mg, and Zn, and lower Cu were observed in the exposed vs control men, while the exposed women had higher Fe and lower Mg, Zn, and Cu than their controls. Our findings confirm that combined exposure to a mixture of VOCs, even at permitted levels, may result in additive or synergistic adverse health effects and related disorders. This raises concern about current risk assessments, which mainly rely on the effects of individual chemicals, and calls for risk assessment approaches that can explain combined exposure to multiple chemicals.

Are changes in olanzapine-induced liver enzyme levels associated with GSTT1, GSTM1, GSTP1, and OGG1 gene polymorphisms?

Aylin Elkama — 2024-02-16

Olanzapine treatment sometimes produces transient liver biochemistry abnormalities, and such drug-induced liver injuries are mainly monitored by measuring blood levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), whereas alpha-glutathione-S-transferase (α-GST) is not routinely measured in clinics, even though it can serve as an earlier and more specific biomarker of liver damage. Susceptibility to drug-induced liver injury can much depend on the gene polymorphisms regulating the activity of DNA detoxification and repair enzymes. The aim of this study was to evaluate which of the three liver enzymes – α-GST, ALT, and AST – is the most sensitive biomarker of olanzapine-induced liver injury and how their blood levels are affected by the GSTT1, GSTM1, GSTP1, and OGG1 gene polymorphisms in 30 olanzapine-treated patients. Contrary to our hypothesis, the increase in serum α-GST levels was not significantly greater than that of the transaminases. ALT turned out to be an earlier biomarker of liver injury than the other two enzymes. No significant association was found between gene polymorphisms and liver enzyme levels, save for GSTP1 Ile/Val + Val/Val and ALT, which points to this genotype as a risk factor for drug-induced liver injury. Future studies might help to identify the underlying mechanisms of transient liver enzyme increase associated with this genotype.

Nanoplastics increase in vitro oestrogenic activity of neurotherapeutic drugs

Lucija Božičević — 2024-03-11

Environmental pollution with plastic nanoparticles (PNPs) has rendered hazard assessment of unintentional human exposure to neurotherapeutic drugs through contaminated water and food ever more complicated. Due to their small size, PNPs can easily enter different cell types and cross different biological barriers, while their high surface-to-volume ratio enables higher adsorption of chemicals. This is how PNPs take the role of a Trojan horse as they enhance bioaccumulation of many different pollutants. One of the health concerns related to water pollution with neurotherapeutic drugs is endocrine disruption, already evidenced for the anticonvulsant drug carbamazepine (Cbz) and antidepressant fluoxetine (Flx). Our study aimed to evaluate endocrine disrupting effects of Cbz and Flx in mixtures with polystyrene nanoparticles (PSNPs) using the in vitro luciferase assay to measure oestrogen receptor activity in T47D-KBluc cells treated with Cbz-PSNPs or Flx-PSNPs mixtures and compare it with the activities observed in cells treated with individual mixture components (Cbz, Flx, or PSNPs). Dose ranges used in the study were 0.1–10 mg/L, 1–100 µmol/L, and 0.1–10 µmol/L for PSNPs, Cbz, and Flx, respectively. Our findings show that none of the individual components activate oestrogen receptors, while the mixtures induce oestrogen receptor activity starting with 0.1 mg/L for PSNPs, 10 µmol/L for Cbz, and 0.5 µmol/L for Flx. This is the first study to evidence that PSNPs increase oestrogen receptor activity induced by neurotherapeutic drugs at their environmentally relevant concentrations and calls for urgent inclusion of complex mixtures in health hazard assessments to inform regulatory response.

Environmental exposure to glyphosate does not inhibit human acetylcholinesterase and butyrylcholinesterase

Dora Kolić — 2024-03-06

Glyphosate has remained the leading herbicide on the global market to date, despite the continuous debate between consumers, scientific community, and regulatory agencies over its carcinogenicity, genotoxicity, environmental persistence, and the role in the development of neurodegenerative disorders. Chemically, glyphosate belongs to a large family of organophosphorus pesticides, which exert a neurotoxic effect by inhibiting acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), enzymes of the cholinergic system essential for maintaining neurotransmission. Although research shows that glyphosate is a weak cholinesterase inhibitor in fish and mammals compared to other OP compounds, no conclusive data exist concerning the inhibition of human AChE and BChE. In our study we analysed its inhibitory potency on human AChE and BChE, by establishing its IC₅₀ and reversible inhibition in terms of dissociation inhibition constants. Glyphosate concentration of 40 mmol/L caused near total inhibition of enzyme activity (approx. 10 % activity remaining). Inhibition dissociation constants (K_i) of glyphosate-AChE and -BChE complexes were 28.4±2.7 mmol/L and 19.3±1.8 mmol/L, respectively. In conclusion, glyphosate shows a slight binding preference for BChE but exhibits inhibition only in a high concentration range. Our results are in line with studies reporting that its neurotoxic effect is not primarily linked to the cholinergic system.

Comparative analysis of organophosphorus versus carbamate pesticide poisoning: a case study

Jia-ding Xia — 2024-02-15

Organophosphorus poisoning is a critical condition that can cause central nervous system depression, respiratory failure, and death early on. As its clinical manifestations closely resemble those of carbamate pesticide poisoning, the aim of this case study is to present a case of misdiagnosis, initially identifying carbofuran poisoning as organophosphate in a patient suspect of a heatstroke. We also present a case of intentional self-poisoning with organophosphate dichlorvos to underline the likelihood of pesticide poisoning in patients exhibiting acute cholinergic symptoms when the ingested substance is not known. In such cases, empirical treatment with atropine and oxime can be started pending timely differential diagnosis to adjust treatment as necessary.

A follow-up on the hesperetin issue in modelling the first electrochemical oxidation potential and antioxidant activity of flavonoids

Ante Miličević — 2024-03-11

Report of the Poison Control Centre for 2023

Željka Babić — 2024-03-14