Archives of Industrial Hygiene and Toxicology <div class="WordSection1"> <p><strong><em>Archives of Industrial Hygiene and Toxicology</em></strong> (Arh Hig Rada Toksikol) is an internationally peer-reviewed biomedical scientific quarterly that publishes contributions relevant to all aspects of environmental and occupational health and toxicology.</p> <p>Indexed in <strong>SCI Expanded</strong>,<strong> Medline</strong>/<strong>PubMed</strong>,<strong> Scopus</strong>, Animal Science Database, Biological Sciences (CSA), BIOSIS Previews, GreenFile, INIS, Pollution Abstracts, Veterinary Science Database, Water Resources Abstracts, EBSCO Academic Search Complete, TEMA, TOXLINE, AGRIS, Food Science and Technology Abstracts – FSTA, and Ergonomic Abstracts.</p> <p><em>Archives</em> is a member of, and subscribes to the principles of, the Committee on Publication Ethics (COPE).</p> <p>Impact Factor:<strong> 1.436</strong></p> <p>5-year Impact Factor:<strong><strong> 1.606</strong></strong></p> </div> Institute for Medical Research and Occupational Health en-US Archives of Industrial Hygiene and Toxicology 0004-1254 Phosphogypsum and its potential use in Croatia: challenges and opportunities <p>Phosphogypsum (PG) is a waste by-product (residue) originating from the production of phosphoric acid and phosphate fertilisers. PG contains chemical and radioactive impurities, which is why it is mostly stockpiled in controlled areas. Worldwide, only about 15&nbsp;% of PG is recycled or reused. Today, policies and business strategies prioritise sustainable development through circular economy, which certainly includes PG. This provides new opportunities for Croatia to manage its PG and make an effort to use it as an additive in different industries, such as agriculture and construction. Due to its chemical and radiological properties, PG can potentially cause problems for the environment and human health. Hence, before using PG, detailed knowledge of potential hazards is necessary to protect people and the environment. The aim of this review is to summarise available data on Croatian PG, compare them with other countries, and to identify knowledge gaps and the lack of data on potential hazardous substances in PG in order to assess the opportunities of using PG in Croatia.</p> Tomislav Bituh Branko Petrinec Božena Skoko Dinko Babić Davor Rašeta Copyright (c) 2021 Tomislav Bituh, Branko Petrinec, Božena Skoko, Dinko Babić, Davor Rašeta 2021-06-14 2021-06-14 72 2 10.2478/aiht-2021-72-3504 Environmental and occupational exposures associated with male infertility <p>The upsurge in male infertility over the last two decades, possibly due to environmental exposure, has raised significant interest, particularly boosted by reports from fertility clinics, which showed that chronic diseases and hereditary or other medical conditions might only partially explain current incidence of male infertility. Both environmental and occupational settings may have a significant role in exposure to complex mixtures of endocrine disruptors (ED), which play a major role in fertility disorders. The aim of this review is to give an insight into the current knowledge on exposure settings which may be associated with male infertility. Our study relied on a systematic search of PubMed, Scopus, and Web of Science for articles published between January 2000 and September 2020. It showed that some well documented factors associated with male infertility include smoking, and physiological disturbances or chronic diseases such as obesity and diabetes, which in turn, may also reflect lifestyle choices and environmental exposures, especially to EDs such as phthalates, bisphenols, pesticides, and flame retardants. However, the number of studies on the aetiology of male infertility is still too low in comparison with the size of affected population. Occupational health follow-ups and medical surveillance do not collect any data on male infertility, even though ED chemicals are part of many technological processes.</p> Tihana Marić Aleksandra Fučić Anna Aghyanian Copyright (c) 2021 Tihana Marić, Aleksandra Fučić, Anna Aghyanian 2021-06-07 2021-06-07 72 2 10.2478/aiht-2021-72-3510 Drug-drug-gene interactions as mediators of adverse drug reactions to diclofenac and statins: a case report and literature review <p>Concomitant treatment with drugs that inhibit drug metabolising enzymes and/or transporters, such as commonly prescribed statins and nonsteroidal anti-inflammatory drugs (NSAIDs), has been associated with prolonged drug exposure and increased risk of adverse drug reactions (ADRs) due to drug-drug interactions. The risk is further increased in patients with chronic diseases/comorbidities who are more susceptible because of their genetic setup or external factors. In that light, we present a case of a 46-year-old woman who had been experiencing acute renal and hepatic injury and myalgia over two years of concomitant treatment with diclofenac, atorvastatin, simvastatin/fenofibrate, and several other drugs, including pantoprazole and furosemide. Our pharmacogenomic findings supported the suspicion that ADRs, most notably the multi-organ toxicity experienced by our patient, may be owed to drug-drug-gene interactions and increased bioavailability of the prescribed drugs due to slower detoxification capacity and decreased hepatic and renal elimination. We also discuss the importance of CYP polymorphisms in the biotransformation of endogenous substrates such as arachidonic acid and their modulating role in pathophysiological processes. Yet even though the risks of ADRs related to the above mentioned drugs are substantially evidenced in literature, pre-emptive pharmacogenetic analysis has not yet found its way into common clinical practice.</p> Nada Božina Lana Ganoci Livija Simicevic Katarina Gvozdanovic Iva Klarica Domjanovic Margareta Fistrek Prlic Tena Kriz Ana Boric Bilusic Mario Laganovic Tamara Bozina Copyright (c) 2021 Nada Božina, Lana Ganoci, Livija Simicevic, Katarina Gvozdanovic, Iva Klarica Domjanovic, Margareta Fistrek Prlic, Tena Kriz, Ana Boric Bilusic, Mario Laganovic, Tamara Bozina 2021-06-07 2021-06-07 72 2 10.2478/aiht-2021-72-3549 Prevalence of five pharmacologically most important CYP2C9 and CYP2C19 allelic variants in the population from the Republic of Srpska in Bosnia and Herzegovina <p>The enzymes of the cytochrome P450 superfamily play a critical role in phase I drug metabolism. Among them, CYP2C9 and CYP2C19 are clinically important, as they can mediate severe toxicity, therapy failure, and increased susceptibility to cancer and other diseases caused by chemicals. The aim of this study was to determine the prevalence of pharmacologically most important allelic variants of the <em>CYP2C9</em> and <em>CYP2C19</em> genes in the general population of the Republic of Srpska (Bosnia and Herzegovina) and to compare them with other populations. For this purpose we determined the genotype profile and allele frequency of 216 randomly selected healthy volunteers using real-time polymerase chain reaction (RT-PCR). The prevalence of the <em>CYP2C9</em> <em>*2</em> and <em>*3</em> alleles was 13.6% and 7.4%, respectively. Based on these frequencies, of the 216 participants four (1.86&nbsp;%) were predicted to be poor metabolisers, 78 (36.11&nbsp;%) intermediate, and the remaining 134 (62.03&nbsp;%) normal metabolisers. Based on the prevalence of <em>CYP2C19</em> <em>*2</em> and <em>*17</em> variants – 16.2% and 20.4%, respectively – nine (4.17&nbsp;%) were predicted to be poor, 57 (26.39&nbsp;%) rapid, and nine (4.17&nbsp;%) ultra-rapid metabolisers. We found no significant differences in allele frequencies in our population and populations from other European countries. These findings suggest that genetically determined phenotypes of <em>CYP2C9</em> and <em>CYP2C19</em> should be taken into consideration to minimise individual risk and improve benefits of drug therapy in the Republic of Srpska.</p> Stojko Vidović Ranko Škrbić Miloš P. Stojiljković Vanja Vidović Jelena Bećarević Svjetlana Stoisavljević-Šatara Nela Maksimović Copyright (c) 2021 Stojko Vidović, Ranko Škrbić, Miloš P. Stojiljković, Vanja Vidović, Jelena Bećarević, Svjetlana Stoisavljević-Šatara, Nela Maksimović 2021-05-21 2021-05-21 72 2 10.2478/aiht-2021-72-3499 Knowledge of and attitudes to occupational and sports medicine among medical students in Zagreb, Croatia <p>Occupational and sports medicine (OSM) education is poorly represented in Croatian university undergraduate medical curricula. Zagreb University medical students are required to take OSM classes for a week on their final year of studies. The classes are organised around team-based learning (TBL). Given that students who attend TBL classes have significantly higher exam scores than students who take lectures <em>ex cathedra</em>, the aim of this study was to assess students' knowledge and attitudes immediately after TBL OSM classes. This cross-sectional study included 162 final-year Zagreb University School of Medicine students taking TBL classes in OSM in the academic year of 2019/2020. They were recruited from 30 September 2019 to 4 March 2020. Participants filled in a 20-item questionnaire compiled by the authors and adapted to the Croatian legislation. Their answers demonstrated positive attitude toward OSM classes and negative attitude toward occupational medicine practice and OSM specialty. They showed moderate interest only for the job of sports physician. Even though they showed sufficient knowledge of OSM immediately after the course was completed, they were moderately satisfied with their knowledge. Our findings call for rethinking the practical aspects of teaching OSM classes in order to promote OSM practice among medical students or at least raise awareness about the importance of prevention of numerous work or sport-related disorders.</p> Roko Žaja Hana Brborović Dominik Oroz Katarina Zahariev Vukšinić Marija Bubaš Tajana Božić Milan Milošević Copyright (c) 2021 Roko Žaja, Hana Brborović, Dominik Oroz, Katarina Zahariev Vukšinić, Marija Bubaš, Tajana Božić, Milan Milošević 2021-06-07 2021-06-07 72 2 10.2478/aiht-2021-72-3535 Differences in fungal contamination of broiler litter between summer and winter fattening periods <p>This study aimed to compare fungal contamination of poultry litter between warm and cold seasons. It was carried out in commercial production conditions over two five-week fattening periods: one in the summer (July-August) and one in the winter (December-January). Broilers were reared on a litter composed of chopped straw and sawdust. Litter fungal concentration and composition were investigated weekly, along with litter temperature, moisture, and pH. Litter concentration of total fungi increased over both fattening periods, with no differences in median concentrations between them. Season also had no effect on yeast, <em>Aspergillus </em>section<em> Nigri, </em>and <em>Cladosporium</em>, <em>Fusarium</em>, and <em>Rhizopus</em> spp. concentrations, while the <em>Aspergillus </em>section<em> Flavi </em>and <em>Aspergillus</em> spp. combined showed higher concentrations in the summer, and <em>Mucor</em> and <em>Penicillium</em> spp. in the winter. Total fungal concentration highly correlated with litter temperature, moisture, and pH, regardless of the season. Our findings can be useful in the assessment and control of potential harmful effect of fungi on the health of poultry and poultry farm workers.</p> Mario Ostović Ivica Ravić Matija Kovačić Anamaria Ekert Kabalin Kristina Matković Ivana Sabolek Željko Pavičić Sven Menčik Danijela Horvatek Tomić Copyright (c) 2021 Mario Ostović, Ivica Ravić, Matija Kovačić, Anamaria Ekert Kabalin, Kristina Matković, Ivana Sabolek, Željko Pavičić, Sven Menčik, Danijela Horvatek Tomić 2021-05-19 2021-05-19 72 2 10.2478/aiht-2021-72-3508 1,4-dihydropyridine derivatives increase mRNA expression of Psma3, Psmb5, and Psmc6 in rats <p>The ubiquitin-proteasome system modifies different cellular and protein functions. Its dysregulation may lead to disrupted proteostasis associated with multiple pathologies and aging. Pharmacological regulation of proteasome functions is already an important part of the treatment of several diseases. 1,4-dihydropyridine (1,4-DHP) derivatives possess different pharmacological activities, including antiaging and neuroprotective. The aim of this study was to investigate the effects of several 1,4-DHP derivatives on mRNA expression levels of proteasomal genes <em>Psma3, Psmb5</em>, and<em> Psmc6</em> in several organs of rats. Rats were treated with metcarbatone, etcarbatone, glutapyrone, styrylcarbatone, AV-153-Na, or AV-153-Ca <em>per os</em> for three days. mRNA expression levels were determined with real-time polymerase chain reaction (PCR). For AV-153-Na and AV-153-Ca, we also determined the expression of the <em>Psma6 </em>gene<em>.</em> In the kidney, metcarbatone, etcarbatone, styrylcarbatone, and AV-153-Na increased the expression of all analysed genes. Glutapyrone increased the expression of <em>Psmb5</em> and <em>Psmc6</em> but did not affect the expression of <em>Psma3.</em> In the blood, glutapyrone increased <em>Psmb5 </em>expression. In the liver, AV-153-Na increased the expression of <em>Psma6</em> and <em>Psmc6</em> but lowered the expression of <em>Psmb5</em>, while AV-153-Ca only increased <em>Psma6 </em>expression. The ability of 1,4-DHP derivatives to increase the expression of proteasome subunit genes might hold a therapeutic potential in conditions associated with impaired proteasomal functions, but further research is needed.</p> Kristīne Dišlere Evita Rostoka Egils Bisenieks Gunars Duburs Natalia Paramonova Nikolajs Sjakste Copyright (c) 2021 Kristīne Dišlere, Evita Rostoka, Egils Bisenieks, Gunars Duburs, Natalia Paramonova, Nikolajs Sjakste 2021-06-07 2021-06-07 72 2 10.2478/aiht-2021-72-3422 Protective effects of oral melatonin against cadmium-induced neurotoxicity in Wistar rats <p>The aim of this study was to investigate the effects of oral melatonin on oxidative/antioxidative parameters and histopathological changes in the hippocampal tissue of Cd-exposed Wistar rats, including malondialdehyde (MDA), glutathione (GSH), tumour necrosis factor-alpha (TNF-α), interleukin (IL-6 and IL-10), and gamma-aminobutyric acid (GABA) levels and catalase (CAT), superoxide dismutase (SOD), and acetylcholinesterase (AChE) activities. Thirty-two male Wistar rats were divided randomly into four groups as follows: untreated control (n=8), cadmium (Cd) (n=8), melatonin (Mlt) (n=8), and Cd+Mlt (CdMlt) (n=8). Cd (2&nbsp;mg/kg) was administered orally by gastric gavage three times a week and Mlt (100&nbsp;mg/kg) five times a week. The control group received standard feed and water only. After four weeks of treatment, the animals were decapitated and tissue samples taken for biochemical and histopathological evaluations. Mlt caused a significant increase in GSH levels and SOD and CAT activities in the CdMlt group compared to the Cd group. Tissue TNF-α and IL-6 levels were significantly higher in the Cd group than other groups (P&lt;0.05). This effect was significantly countered by Mlt in the CdMlt group (P&lt;0.05). GABA concentrations were significantly higher in the Mlt than other groups (P&lt;0.05). Our findings clearly evidence the protective effects of melatonin against Cd-induced neurotoxicity in rats.</p> Ihsan Kısadere Mehmet Faruk Aydın Mustafa Usta Nurcan Donmez Copyright (c) 2021 Ihsan Kısadere, Mehmet Faruk Aydın, Mustafa Usta, Nurcan Donmez 2021-06-07 2021-06-07 72 2 10.2478/aiht-2021-72-3513 Pro-oxidant potency of clothianidin in rainbow trout <p>Clothianidin is a systemic neonicotinoid insecticide interfering with the central nervous system by acting as a nicotinic acetylcholine receptor <em>agonist. Although previous studies on fish report low toxicity, its proven toxic potential for aquatic invertebrates and lack of data on its effect on juvenile fish have prompted us to investigate its adverse effects in environmentally relevant concentrations of </em>3, 15 and 30&nbsp;µg/L<em> for 7, 14 and 21 days on heart and spleen tissues of 10-month-old rainbow trout (Oncorhynchus mykiss). We detected a</em> conspicuous increase in protein carbonyl and malondialdehyde (MDA) levels, which triggered antioxidant response of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), resulting in increased levels of glutathione (GSH). Clothianidin inhibited the activity of acetylcholinesterase (AChE) and lowered tissue protein levels. Heart tissue weight increased, while that of spleen decreased significantly. The effects were time- and concentration-dependent. What raises particular concern is the inhibition of AChE in the trout, even though clothianidin is claimed to be selective for insect receptors. Increased antioxidant activity in response to oxidative stress was clearly insufficient to keep MDA and protein carbonyl at normal levels, which evidences the pro-oxidant potency of the insecticide. All this calls for further investigation into potential adverse effects on biological pathways in different fish species.</p> Tarek Fakhereddin Demet Doğan Copyright (c) 2021 Tarek Fakhereddin, Demet Doğan 2021-05-21 2021-05-21 72 2 10.2478/aiht-2021-72-3522