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 Toxicological properties of Δ9-tetrahydrocannabinol and cannabidiol <p><em>Cannabis sativa</em> L. contains more than 100 phytocannabinoids that can interact with cannabinoid receptors CB<sub>1</sub> and CB<sub>2</sub>. None of the cannabinoid receptor ligands is entirely CB<sub>1</sub>- or CB<sub>2</sub>-specific. The effects of cannabinoids therefore differ not just because of different potency at cannabinoid receptors but also because they can interact with other non-CB<sub>1</sub> and non-CB<sub>2</sub> targets, such as TRPV1, GPR55, and GPR119. The most studied phytocannabinoid is Δ<sup>9</sup>-tetrahydrocannabinol (THC). THC is a partial agonist at both cannabinoid receptors, but its psychotomimetic effect is produced primarily via activation of the CB<sub>1</sub> receptor, which is strongly expressed in the central nervous system, with the noteworthy exception of the brain stem. Although acute cognitive and other effects of THC are well known, the risk of irreversible neuropsychological effects of THC needs further research to elucidate the association. Unlike THC, phytocannabinoid cannabidiol (CBD) does not appear to have psychotomimetic effects but may interact with some of the effects of THC if taken concomitantly. CBD administered orally has recently undergone well-controlled clinical trials to assess its safety in the treatment of paediatric epilepsy syndromes. Their findings point to increased transaminase levels as a safety issue that calls for postmarketing surveillance for liver toxicity. The aim of this review is to summarise what is known about acute and chronic toxicological effects of both compounds and address the gaps in knowledge about the safety of exogenous cannabinoids that are still open.</p> Katarina Černe Copyright (c) 2020 Katarina Černe 2020-03-13 2020-03-13 71 1 10.2478/aiht-2020-71-3301 A regulatory take on cannabis and cannabinoids for medicinal use in the European Union <p>The discovery of the endocannabinoid system has raised public interest in the medicinal use of cannabis, phytocannabinoids, and synthetic cannabinoids, which has always been closely regulated due to their psychotropic effects and potential abuse. The review takes a quick look at the current legal framework in the European Union, which regulates cannabis use and cultivation for medicinal purposes in line with the United Nations Conventions on the production, trade, and use of cannabis, phytocannabinoids, and synthetic cannabinoids. And while the EU legislation precisely defines requirements and marketing authorisation procedures for medicinal products for all EU member states, there is no common regulatory framework for magistral and officinal preparations containing cannabinoids, as they are exempt from marketing authorisation. Instead, their regulation is left to each member state, and it is quite uneven at this point, mainly due to cultural and historical differences between the countries, leading to different access to non-authorised medicinal products. Therefore, to meet great public interest, harmonised approaches on cannabinoid-containing products without marketing authorisation would be welcome to level the playing field in the EU.</p> Metoda Lipnik-Štagelj Barbara Razinger Copyright (c) 2020 Metoda Lipnik-Štagelj, Barbara Razinger 2020-02-27 2020-02-27 71 1 10.2478/aiht-2020-71-3302 Gamma-hydroxybutyrate abuse: pharmacology and poisoning and withdrawal management <p>Gamma-hydroxybutyrate (GHB) is a central nervous system depressant primarily used as a recreational drug of abuse, but also for the treatment of narcolepsy with cataplexy in adult patients and as an adjuvant for control of alcohol withdrawal syndrome. The main aim of this review is to summarise updated knowledge about GHB pharmacokinetics and pharmacodynamics, acute poisoning, and clinical features of GHB withdrawal syndrome, its diagnosis and medical treatment. The most common clinical signs and symptoms of acute poisoning include sleepiness to deep coma, bradycardia, hypotension, and respiratory failure. Therapy is essentially supportive and based on continuous monitoring of vital signs. GHB withdrawal syndrome shares patterns with other withdrawal syndromes such as alcohol withdrawal and is sometimes difficult to distinguish, especially if toxicological tests are GHB-negative or cannot be performed. There are no official detoxification protocols for GHB withdrawal syndrome, but its therapy is based on benzodiazepine. When benzodiazepine alone is not effective, it can be combined with barbiturates or antipsychotics. Information about abuse and distribution of GHB and its precursors/analogues among the general population is still limited. Their prompt identification is therefore crucial in conventional and non-conventional biological matrices, the latter in particular, to clarify all the issues around this complex molecule.</p> Simona Zaami Renata Beck Natale Mario di Luca Alfredo Fabrizio Lo Faro Enrico Marinelli Copyright (c) 2020 Simona Zaami, Renata Beck, Natale Mario di Luca, Alfredo Fabrizio Lo Faro, Enrico Marinelli 2020-03-24 2020-03-24 71 1 10.2478/aiht-2020-71-3314 Metallothionein 2A gene polymorphisms in relation to diseases and trace element levels in humans <p>Human metallothioneins are a superfamily of low molecular weight intracellular proteins, whose synthesis can be induced by essential elements (primarily Zn and Cu), toxic elements and chemical agents, and stress-producing conditions. Of the four known isoforms in the human body MT2 is the most common. The expression of metallothioneins is encoded by a multigene family of linked genes and can be influenced by single nucleotide polymorphisms (SNPs) in these genes. To date, 24 SNPs in the <em>MT2A</em> gene have been identified with the incidence of about 1&nbsp;% in various population groups, and three of them were shown to affect physiological and pathophysiological processes. This review summarises current knowledge about these three SNPs in the <em>MT2A</em> gene and their associations with element concentrations in the body of healthy and diseased persons. The most investigated SNP is rs28366003 (<em>MT2A</em> −5 A/G). Reports associate it with longevity, cancer (breast, prostate, laryngeal, and in paranasal sinuses), and chronic renal disease. The second most investigated SNP, rs10636 (<em>MT2A</em> +838G/C), is associated with breast cancer, cardiovascular disease, and type 2 diabetes. Both are also associated with several metal/metalloid concentrations in the organism. The third SNP, rs1610216 (<em>MT2A</em> −209A/G), has been studied for association with type 2 diabetes, cardiomyopathy, hyperglycaemia, and Zn concentrations. Metallothionein concentrations and <em>MT2A</em> polymorphisms have a potential to be used as biomarkers of metal exposure and clinical markers of a number of chronic diseases. This potential needs to be studied and verified in a large number of well-defined groups of participants (several hundreds and thousands) with a focus on particular physiological or pathological condition and taking into consideration other contributing factors, such as environmental exposure and individual genetic and epigenetic makeup.</p> Ankica Sekovanić Jasna Jurasović Martina Piasek Copyright (c) 2020 Ankica Sekovanić, Jasna Jurasović, Martina Piasek 2020-03-18 2020-03-18 71 1 10.2478/aiht-2020-71-3349 Experimental central composite design-based dispersive liquid-liquid microextraction for HPLC-DAD determination of diazinon in human urine samples: method development and validation <p>Diazinon poisoning is an important issue in occupational, clinical, and forensic toxicology. While efficient, sensitive, and specific enough to analyse diazinon in biological samples, current methods are time-consuming and too expensive for routine analysis. The aim of this study was therefore to design and validate a simple dispersive liquid-liquid microextraction (DLLME) for the preparation of urine samples to be analysed for diazinon with high performance liquid chromatography with diode-array detector (HPLC-DAD) to establish diazinon exposure and poisoning. To do that, we first identified critical parameters (type and volume of extraction and disperser solvents, pH, surfactant, and salt concentrations) in preliminary experiments and then used central composite design to determine the best experimental conditions for DLLME-HPLC-DAD. For DLLME they were 800&nbsp;µL of methanol (disperser solvent) and 310&nbsp;µL of toluene (extraction solvent) injected to the urine sample rapidly via a syringe. The sample was injected into a HPLC-DAD (C<sub>18</sub> column, 250×4.6&nbsp;mm, 5&nbsp;μm), and the mobile phase was a mixture of acetonitrile and buffer (63:37&nbsp;v/v, pH&nbsp;3.2; flow rate: 1&nbsp;mL/min). Standard calibration curves for diazinon were linear with the concentration range of 0.5–4&nbsp;µg/mL, yielding a regression equation Y=0.254X+0.006 with a correlation coefficient of 0.993. The limit of detection and limit of quantification for diazinon were 0.15&nbsp;µg/mL and 0.45&nbsp;µg/mL, respectively. The proposed method was accurate, precise, sensitive, and linear over a wide range of diazinon concentrations in urine samples. This method can be employed for diazinon analysis in routine clinical and forensic toxicology settings.</p> Reza Mohammadzaheri Mehdi Ansari Dogaheh Maryam Kazemipour Kambiz Soltaninejad Copyright (c) 2020 Reza Mohammadzaheri, Mehdi Ansari Dogaheh, Maryam Kazemipour, Kambiz Soltaninejad 2020-02-05 2020-02-05 71 1 10.2478/aiht-2020-71-3292 Chiral separation of beta-blockers by high-performance liquid chromatography and determination of bisoprolol enantiomers in surface waters <p>Beta-blockers are chiral compounds with enantiomers that have different bioactivity, which means that while one is active, the other can be inactive or even harmful. Due to their high consumption and incomplete degradation in waste water, they may reach surface waters and affect aquatic organisms. To address this issue we developed a chromatographic method suitable for determining beta-blocker enantiomers in surface waters. It was tested on five beta-blockers (acebutolol, atenolol, bisoprolol, labetalol and metoprolol) and validated on bisoprolol enantiomers. Good enantioseparation of all analysed beta-blockers was achieved on the Chirobiotic V column with the mobile phase composed of methanol/acetic acid/triethylamine (100/0.20/0.15 v/v/v) at a flow rate of 0.5&nbsp;mL/min and column temperature of 45&nbsp;°C. Method proved to be linear in the concentration range from 0.075&nbsp;µg/mL to 5&nbsp;µg/mL, and showed good recovery. The limits of bisoprolol enantiomer detection were 0.025&nbsp;µg/mL and 0.026&nbsp;µg/mL and of quantification 0.075&nbsp;µg/mL and 0.075&nbsp;µg/mL. Despite its limitations, it seems to be a promising method for bisoprolol enantiomer analysis in surface water samples. Further research could focus on waste water analysis, where enantiomer concentrations may be high. Furthermore, transferring the method to a more sensitive one such as liquid chromatography coupled with tandem mass spectrometry and using ammonium acetate as the mobile phase additive instead of acetic acid and triethylamine would perhaps yield much lower limits of detection and quantification.</p> Marijana Pocrnić Martin Ansorge Magda Dovhunova Iva Habinovec Eva Tesarova Nives Galić Copyright (c) 2020 Marijana Pocrnić, Martin Ansorge, Magda Dovhunova, Iva Habinovec, Eva Tesarova, Nives Galić 2020-02-21 2020-02-21 71 1 10.2478/aiht-2020-71-3318 Soft nanotechnology: the potential of polyelectrolyte multilayers against E. coli adhesion to surfaces <p>Preventing bacterial attachment to surfaces is the most efficient approach to controlling biofilm proliferation. The aim of this study was to compare anti-adhesion potentials of 5 and 50&nbsp;mmol/L polyelectrolyte multilayers of poly(allylamine&nbsp;hydrochloride)/poly(sodium&nbsp;4–styrenesulfonate), poly(4-vinyl-<em>N</em>-ethylpyridinium&nbsp;bromide)/poly(sodium&nbsp;4–styrenesulfonate), and poly(4-vinyl-<em>N</em>-isobutylpyridinium&nbsp;bromide)/poly(sodium&nbsp;4–styrenesulfonate) against <em>Escherichia coli</em>. Glass surface was covered with five polyelectrolyte layers and exposed to bacterial suspensions. Poly(4-vinyl-<em>N</em>-ethylpyridinium bromide)/poly(sodium 4–styrenesulfonate) was the most effective against bacterial adhesion, having reduced it by 60&nbsp;%, followed by poly(4-vinyl-<em>N</em>-isobutylpyridinium bromide)/poly(sodium&nbsp;4–styrenesulfonate) (47&nbsp;%), and poly(allylamine&nbsp;hydrochloride)/poly(sodium&nbsp;4–styrenesulfonate) (38&nbsp;%). Polyelectrolyte multilayers with quaternary amine groups have a significant anti-adhesion potential and could find their place in coatings for food, pharmaceutical, and medical industry.</p> Rok Fink Martina Oder Jasmina Jukić Nikola Cindro Josip Požar Copyright (c) 2020 Rok Fink, Martina Oder, Jasmina Jukić, Nikola Cindro, Josip Požar 2020-03-09 2020-03-09 71 1 10.2478/aiht-2020-71-3319 Cytotoxic and mutagenic potential of juglone: a comparison of free and nano-encapsulated form <p>Despite its evidenced beneficial herbicidal, antibacterial, antiviral, antifungal, and antioxidant effects, the application of juglone (5-hydroxy-1,4,-naphthoquinone) is limited due to its low water solubility and allelopathic and toxic effects. In recent years, research has aimed to overcome these limitations by increasing its solubility and controlling its release through nanoparticular systems. This is the first study to have synthesised and characterised juglone-loaded polymeric nanoparticles and compared them with free juglone for cytotoxicity in mouse (L929 fibroblasts) and alfalfa cells and for mutagenic potential in Salmonella typhimurium TA98/100. Mouse and plant cells treated with free and nano-encapsulated juglone showed a decrease in cell viability in a dose and time-dependent manner, but this effect was significantly lower with the nano-encapsulated form at lower doses. In the TA98 strain with S9, nano-encapsulated juglone did not exhibit mutagenic effects, unlike the free form. Since all results show that juglone encapsulation with polymeric nanoparticles reduced the toxic and mutagenic effects, it has a promising potential to be applied in medicine, food safety, and agriculture.</p> Semiha Erisen Tulin Arasoglu Banu Mansuroglu Ismail Kocacaliskan Serap Derman Copyright (c) 2020 Semiha Erisen, Tulin Arasoglu, Banu Mansuroglu, Ismail Kocacaliskan, Serap Derman 2020-02-11 2020-02-11 71 1 10.2478/aiht-2020-71-3344 Reproductive disorders in male rats induced by high-fructose consumption from juvenile age to puberty <p>There is compelling evidence that a hypercaloric, high-fructose diet can cause metabolic syndrome (MetS) and a whole range of other metabolic changes. In the context of androgen deficiency, MetS in boys merits special attention, but the effects of fructose-rich diet in youth on future male reproductive function are still poorly evidenced. The aim of this study was to address this issue and analyse the effects of high-fructose intake starting from weaning to puberty (postnatal day 23 up to 83) on the reproductive function of male rats. For this purpose juvenile male Wistar rats were divided in two groups: control and the group receiving 10 % fructose solution instead of drinking water. Reproductive function was evaluated in terms of fertility, sperm count, testes/epididymis morphology, and serum sex hormones. The fructose-treated group showed a decrease in testosterone and twofold increase in <em>luteinising</em> and follicle-stimulating hormone levels in the serum. This was accompanied with lower testis/epididymis weights, sperm count, and changed testis/epididymis morphology. Their fertility remained unchanged, but the fertility of females mating with these males diminished. In addition, pre-implantation and post-implantation embryonic death rate rose in these females. Our results have confirmed that high fructose consumption from early age until puberty can impair the reproductive function of male rats, and call for further animal and epidemiological investigation.</p> Oleksandr Ye. Tkachenko Ganna M. Shayakhmetova Anatoliy V. Matvienko Valentina M. Kovalenko Copyright (c) 2020 Oleksandr Ye. Tkachenko, Ganna M. Shayakhmetova, Anatoliy V. Matvienko, Valentina M. Kovalenko 2020-02-19 2020-02-19 71 1 10.2478/aiht-2020-71-3303 Effect of urine adulterants on commercial drug abuse screening test strip results <p>Immunochromatographic strips for urine drug screening tests (UDSTs) are common and very suitable for drug abuse monitoring, but are also highly susceptible to adulterants kept in the household, which can significantly alter test results. The aim of this study was to see how some of these common adulterants affect UDST results in practice and whether they can be detected by sample validity tests with pH and URIT&nbsp;11G test strips. To this end we added household chemicals (acids, alkalis, oxidizing agents, surfactants, and miscellaneous substances) to urine samples positive for amphetamine, 3,4-methylenedioxymethamphetamine (MDMA), tetrahydrocannabinol, heroin, cocaine, or benzodiazepines (diazepam or alprazolam) and tested them with one-component immunochromatographic UDST strips. The UDST for cocaine resisted adulteration the most, while the cannabis test produced the most false negative results. The most potent adulterant that barely changed the physiological properties of urine specimens and therefore escaped adulteration detection was vinegar. Besides lemon juice, it produced the most false negative test results. In conclusion, some urine adulterants, such as vinegar, could pass urine specimen validity test and remain undetected by laboratory testing. Our findings raise concern about this issue of preventing urine tampering and call for better control at sampling, privacy concerns notwithstanding, and better sample validity tests.</p> Ivana Rajšić Dragana Javorac Simona Tatović Aleksandra Repić Danijela Đukić-Ćosić Snežana Đorđević Vera Lukić Zorica Bulat Copyright (c) 2020 Danijela Đukić-Ćosić, Ivana Rajšić, Dragana Javorac, Simona Tatović, Aleksandra Repić, Danijela Đukić-Ćosić, Snežana Đorđević, Vera Lukić, Zorica Bulat 2020-03-24 2020-03-24 71 1 10.2478/aiht-2020-71-3315