Estimation of Cutoff Values of Cotinine in Urine and Saliva for Pregnant Women in Poland

Setting appropriate cutoff values and the use of a highly sensitive analytical method allow for correct classification of the smoking status. Urine-saliva pairs samples of pregnant women in the second and third trimester, and saliva only in the first trimester were collected. Offline SPE and LC-ESI-MS/MS method was developed in the broad concentration range (saliva 0.4–1000 ng/mL, urine 0.8–4000 ng/mL). The mean recoveries were 3.7±7.6% for urine and 99.1±2.6% for saliva. LOD for saliva was 0.12 ng/mL and for urine 0.05 ng/mL; LOQ was 0.4 ng/mL and 0.8 ng/mL, respectively. Intraday and interday precision equaled, respectively, 1.2% and 3.4% for urine, and 2.3% and 6.4% for saliva. There was a strong correlation between salivary cotinine and the uncorrected cotinine concentration in urine in the second and third trimesters of pregnancy. The cutoff values were established for saliva 12.9 ng/mL and urine 42.3 ng/mL or 53.1 μg/g creatinine with the ROC curve analysis. The developed analytical method was successfully applied to quantify cotinine, and a significant correlation between the urinary and salivary cotinine levels was found. The presented cut-off values for salivary and urinary cotinine ensure a categorization of the smoking status among pregnant women that is more accurate than self-reporting

Bis(2-ethylhexyl) phthalate. Documentation of proposed values of occupational exposure limits (OELs)

Ftalan bis(2-etyloheksylu) (DEHP) był powszechnie stosowany w przeszłości, głównie jako plastyfikator. Narażenie zawodowe na DEHP występuje w czasie jego produkcji oraz stosowania, zaś narażenie środowiskowe jest związane z produktami zawierającymi ten związek oraz ze spożywaniem zanieczyszczonej żywności lub wody. Unia Europejska wprowadziła zakaz obrotu produktów zawierających DEHP w stężeniu ≥0,1%. Wchłanianie tego flatalanu może zachodzić drogą pokarmową i inhalacyjną, przechodzi on również przez barierę łożyskową oraz do mleka matki. Dane epidemiologiczne wskazują na związek między narażeniem na DEHP (zarówno zawodowym, jak i środowiskowym) a funkcjonowaniem męskiego układu rozrodczego. Nie wykazano bezpośredniej zależności między narażeniem na DEHP a bezpłodnością. W badaniach na zwierzętach za najczulszy skutek toksyczności przewlekłej tego związku uznano zaburzenia spermatogenezy u szczurów. Jako podstawę do zaproponowania wartości NDS dla ftalanu bis(2-etyloheksylu) przyjęto toksyczne działanie na męski układ rozrodczy obserwowane u szczura (NOAEL = 5,8 mg/kg mc./dzień). Proponuje się przyjęcie wartości NDS dla ftalanu bis(2-etyloheksylu) na poziomie 0,8 mg/m³ Brak jest podstaw do ustalenia wartości NDSCh oraz DSB. Proponuje się notację „Ft” – substancja działająca szkodliwie na rozrodczość. Z powodu niewielkiego wchłaniania DEHP drogą dermalną brak jest podstaw do przyjęcia notacji „skóra”. Zakres tematyczny artykułu obejmuje zagadnienia zdrowia oraz bezpieczeństwa i higieny środowiska pracy będące przedmiotem badań z zakresu nauk o zdrowiu i inżynierii środowiskaBis(2-ethylhexyl) phthalate (DEHP) has been widely used in the past mainly as a plasticizer. Occupational exposure to DEHP occurs during its production and use, and environmental exposure is related to products containing DEHP and contaminated food/water. The European Union has banned products containing DEHP in concentrations ≥0.1%. Absorption of DEHP may occur via the oral and inhalation routes. DEHP crosses the placental barrier and passes into breast milk. Epidemiological data indicate an association between DEHP occupational and environmental exposures and male reproductive function. However, no direct relationship between DEHP exposure and infertility can be identified. In animal studies, impaired spermatogenesis in rats has been considered as the most sensitive effect of chronic toxicity of DEHP. The proposed MAC value for bis(2-ethylhexyl) phthalate (0.8 mg/m³) is based on toxic effects on the male reproductive system demonstrated in a chronic study on rats (NOAEL = 5.8 mg/kg bw/day). There is no basis for setting the STEL value (no local irritation) and BEI value. Due to the low dermal absorption of DEHP there is no basis for a “skin” notation, but “R” notation is required (toxic to reproduction). This article discusses the problems of occupational safety and health, which are covered by health sciences and environmental engineering

Bisphenol A – Application, sources of exposure and potential risks in infants, children and pregnant women

Bisphenol A (BPA) is used in the chemical industry as a monomer in the production of plastics. It belongs to a group of compounds that disturb some of the functions of human body, the endocrine system in particular. Extensive use of BPA in manufacturing products that come in contact with food increases the risk of exposure to this compound, mainly through the digestive tract. Literature data indicate that exposure to bisphenol A even at low doses may result in adverse health effects. The greatest exposure to BPA is estimated among infants, children and pregnant women. The aim of this review is to show potential sources of exposure to bisphenol A and the adverse health effects caused by exposure to this compound in the group of particular risk

An Assessment of Metallothionein–Cadmium Binding in Rat Uterus after Subchronic Exposure Using a Long–Term Observation Model

Cadmium (Cd) is an environmental pollutant known to pose a public health issue. The mechanism of Cd toxicity on the uterus, including the protective role of metallothionein (MT), is still not fully understood. The aim of the study was to evaluate the degree of MT-Cd binding in the uterus of rats exposed per os to Cd at daily doses of 0.09, 0.9, 1.8 and 4.5 mg Cd/kg b.w. for 90 days. To assess the permanence of the bond, the rats were observed over long observation periods: 90 and 180 days after termination of exposure. Additionally, uterine concentration of Zn, Cu, Ca, Mg was determined. Cd leads immediately after exposure to a max. 30-fold increase in the concentration of Cd in the uterus, with only small amounts being bound to MT. After 90 days following termination of exposure, and especially after 180 days, an increase in MT-Cd concentration was noted for the three highest doses; even so, the degree of Cd binding by MT was still small. Additionally, the accumulation of Cd in the uterus disturbs the homeostasis of determined essential elements, manifested by a significant increase in Cu concentration and a decrease in Zn, Mg and Ca, especially 180 days after termination of exposure. The obtained results indicate that MT has only a slight protective role in the uterus and that Cd ions may have harmful effects not related to MT: directly on the uterine tissue, and indirectly by disturbing the homeostasis of its essential elements

Bisphenol A – Application, sources of exposure and potential risks in infants, children and pregnant women

Bisphenol A (BPA) is used in the chemical industry as a monomer in the production of plastics. It belongs to a group of compounds that disturb some of the functions of human body, the endocrine system in particular. Extensive use of BPA in manufacturing products that come in contact with food increases the risk of exposure to this compound, mainly through the digestive tract. Literature data indicate that exposure to bisphenol A even at low doses may result in adverse health effects. The greatest exposure to BPA is estimated among infants, children and pregnant women. The aim of this review is to show potential sources of exposure to bisphenol A and the adverse health effects caused by exposure to this compound in the group of particular risk

The Role of Zinc in Selected Female Reproductive System Disorders

Zinc is an essential microelement that plays many important functions in the body. It is crucial for the regulation of cell growth, hormone release, immunological response and reproduction. This review focuses on its importance in the reproductive system of women of reproductive and postmenopausal ages, not including its well described role in pregnancy. Only recently, attention has been drawn to the potential role of zinc in polycystic ovary syndrome (PCOS), dysmenorrhea, or endometriosis. This review is mainly based on 36 randomized, controlled studies on reproductive, pre- and post-menopausal populations of women and on research trying to explain the potential impact of zinc and its supplementation in the etiology of selected female reproductive system disorders. In women with PCOS, zinc supplementation has a positive effect on many parameters, especially those related to insulin resistance and lipid balance. In primary dysmenorrhea, zinc supplementation before and during each menstrual cycle seems to be an important factor reducing the intensity of menstrual pain. On the other hand, little is known of the role of zinc in endometriosis and in postmenopausal women. Therefore, further studies explaining the potential impact of zinc and its supplementation on female reproductive system would be highly advisable and valuable

4-Chloro-2-toliloamina i jej chlorowodorek (w przeliczeniu na 4-chloro-2-toliloaminę) – frakcja wdychalna. Dokumentacja proponowanych dopuszczalnych wielkości narażenia zawodowego

4-Chloro-2-toliloamina (4-COT, 4-chloro-o-toluidyna) i jej chlorowodorek są ciałami stałymi. W warunkach laboratoryjnych 4-COT jest stosowana jako barwnik w immunochemii i w biologii molekularnej. W Polsce narażenie na 4-chloro-2-toliloaminę i/lub jej chlorowodorek zgłaszały wyłącznie laboratoria. Zgłoszona do rejestru liczba narażonych na 4-COT wyniosła 262 osoby w 2012 r., a w 2017 – 12 osób. W warunkach narażenia zawodowego 4-COT wchłania się głównie przez skórę i drogi oddechowe. U osób narażonych stwierdzono działanie methemoglobinotwórcze związku oraz występowanie objawów ze strony dróg moczowych w postaci ostrego, krwotocznego zapalenia pęcherza moczowego. Mediany dawek letalnych 4-COT dla gryzoni (drogą pokarmową) wynoszą 860 ÷ 1 058 mg/kg mc. Związek ten wywiera także umiarkowane działanie drażniące na skórę i oczy. Dane na temat toksyczności podprzewlekłej i przewlekłej 4-COT dla zwierząt wskazują na toksyczność ogólnoustrojową. 4-COT wykazuje działanie mutagennie i genotoksycznie zarówno w warunkach in vivo, jak i in vitro. Powoduje uszkodzenie DNA oraz tworzy addukty z DNA. W dostępnym piśmiennictwie nie ma informacji na temat wpływu 4-COT na rozrodczość ludzi. Nie ma danych na temat embriotoksyczności i teratogenności tego związku. W doświadczeniu na myszach wykazano, że 4-COT nie ma wpływu na potencjał rozrodczy samców oraz rozwój potomstwa. U osób zawodowo narażonych na 4-COT stwierdzano istotny wzrost występowania raka pęcherza moczowego. Brak jest danych o wielkości stężeń 4-COT, na jakie osoby te były narażone. 4-COT jest związkiem rakotwórczym dla zwierząt. 4-COT ma zharmonizowaną klasyfikację jako substancja rakotwórcza kategorii zagrożenia 1B. IARC zaliczyła 4-COT do grupy 2A – związków o prawdopodobnym działaniu rakotwórczym na człowieka. W dostępnym piśmiennictwie nie znaleziono danych dotyczących wydajności i wchłaniania 4-COT różnymi drogami. U zwierząt metabolizm 4-COT może przebiegać szlakami N-acetylacji i N-hydroksylacji/N-oksydacji, przy udziale CYP1A1 i/lub CYP1A2, do aktywnych metabolitów. Związek jest wydalany głównie z moczem w postaci niezmienionej oraz metabolitów, np. kwasu 5-chloroantranilowego i 4-chloro-2-metyloacetanilidu. Nie ma danych na temat toksykokinetyki 4-COT u ludzi. W większości państw nie ustalono wartości dopuszczalnych stężeń dla 4-COT w środowisku pracy ze względu na jej potencjał rakotwórczy. Jedynym krajem europejskim, w którym ustalono wartość normatywu, jest Chorwacja, gdzie wartość NDS ustalono na poziomie 0,01 mg/m³ z jednoczesną notacją „skóra”. Podstawy ustalenia tej wartości nie są znane. Jako podstawę do zaproponowania wartości NDS przyjęto działanie rakotwórcze 4-COT. Wartość NDS wyprowadzono przy wykorzystaniu współczynnika SF = 0,27 (mg/kg-dzień)-1, ustalonego na podstawie występowania nowotworów naczyniowych u myszy. Przy założonym ryzyku R = 10-4 obliczona wartość NDS wynosi 0,02 mg/m³ . Nie znaleziono podstaw do ustalenia wartości chwilowej NDSCh i dopuszczalnego stężenia w materiale biologicznym (DSB). Narażenie przez skórę może mieć znaczny udział w ilości związku pobranej przez pracowników, wymagana jest więc notacja „skóra”. Zakres tematyczny artykułu obejmuje zagadnienia zdrowia oraz bezpieczeństwa i higieny środowiska pracy będące przedmiotem badań z zakresu nauk o zdrowiu oraz inżynierii środowiska.4-Chloro-o-toluidine (4-COT) and its hydrochloride are solids. 4-Chloro-o-toluidine is currently used as a dye in immunochemistry and molecular biology. In Poland, exposure to 4-COT and/or its hydrochloride was only reported by laboratories. The number of people exposed was 262 in 2012 and 12 in 2017. Under occupational exposure conditions, 4-COT is absorbed through the skin and airways. Methemoglobinogenic effects and acute hemorrhagic cystitis were diagnosed in exposed individuals. Median lethal doses after administration of 4-COT by the oral route to rodents were 860-1058 mg/kg b.w. The compound had a moderately irritating effect on skin and eyes. Studies of subchronic and chronic toxicity in animals indicate systemic toxicity. 4-COT had mutagenic and genotoxic effects in vivo as in vitro. It caused damage and adducts of DNA. There are no data on the effects of 4-COT on human reproduction and no data on its embryotoxicity and teratogenicity. In mice, 4-COT did not affect the reproductive potential of males or the development of their offspring. A significant increase in the incidence of bladder cancer was observed in individuals occupationally exposed to 4-COT. There are no data on the concentrations of 4-COT to which these individuals were exposed. 4-COT is an animal carcinogen. 4-COT is classified as a category 1B carcinogen. IARC has classified 4-COT into group 2A – compounds with probable carcinogenic effects in humans. No data are available on the rate and efficiency of absorption of 4-COT by different routes. In animals, the metabolism of 4-COT may be via N-acetylation and N-hydroxylation/N-oxidation routes, involving CYP1A1 and/or CYP1A2, to active metabolites. The compound is excreted mainly with urine in unaltered form and the metabolites, e.g. 5-chloroantranilic acid and 4-chloro-2-methylacetanilide. There are no data on the toxicokinetic of 4-COT in humans. In most countries, no MAC values have been established due to the carcinogenic potential of 4-COT. Only in Croatia the MAC value was set at 0.01 mg/m³ , with the notation ‘skin’. The basis for establishing this value is unknown. The carcinogenic effect of 4-COT has been used as a basis for proposing the MAC values. The value of MAC was derived from the factor SF = 0.27 (mg/kg-day)-1, determined on the basis of the occurrence of vascular tumors in mice. At the assumed risk of R = 10-4, the calculated MAC value is 0.02 mg/m³ . No basis for establishing STEL and BEI values was found. As dermal absorption may be as important as inhalation exposure, a “skin” notation is required. This article discusses the problems of occupational safety and health, which are covered by health sciences and environmental engineering

Optimization of ultra-performance liquid chromatography (UPLC) with fluorescence detector (FLD) method for the quantitative determination of selected neurotransmitters in rat brain

Background: Glutamate (Glu) and γ-aminobutyric acid (GABA) are the main neurotransmitters in the central nervous system for excitatory and inhibitory processes, respectively. Monitoring these neurotransmitters is an essential tool in establishing pathological functions, among others in terms of occupational exposure to toxic substances. Material and Methods: We present modification of the HPLC (high-performance liquid chromatography) to the UPLC (ultra-performance liquid chromatography) method for the simultaneous determination of glutamate and γ-aminobutyric acid in a single injection. The isocratic separation of these neurotransmitter derivatives was performed on Waters Acquity BEH (ethylene bridged hybrid) C18 column with particle size of 1.7 μm at 35°C using a mobile phase consisting of 0.1 M acetate buffer (pH 6.0) and methanol (60:40, v/v) at a flow rate of 0.3 ml/min. The analytes were detected with the fluorescence detector (FLD) using derivatization with o-phthaldialdehyde (OPA), resulting in excitation at 340 nm and emission at 455 nm. Results: Several validation parameters including linearity (0.999), accuracy (101.1%), intra-day precision (1.52–1.84%), inter-day precision (2.47–3.12%), limit of detection (5–30 ng/ml) and quantification (100 ng/ml) were examined. The developed method was also used for the determination of these neurotransmitters in homogenates of selected rat brain structures. Conclusions: The presented UPLC-FLD is characterized by shorter separation time (3.5 min), which is an adaptation of the similar HPLC methods and is an alternative for more expensive references techniques such as liquid chromatography coupled with tandem mass-spectrometry (LC-MS/MS) methods. Med Pr 2017;68(5):583–59

The effect of prenatal exposure on disposition of hexachloronaphthalene in female Wistar rats and fetal compartment

Objectives Due to structural and toxicological similarities to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), polychlorinated naphthalenes (PCNs) were included in the Stockholm Convention on Persistent Organic Pollutants (POPs) in 2015. Hexachloronaphthalene (HxCN) is considered to be one of the most toxic congeners of PCNs. The objective of this study was to determine the maternal and fetal tissue concentrations of hexachloronaphthalene after a single administration. Material and Methods Pregnant female Outbred Wistar rats were used for the study. The [ 14 C]-HxCN was administered in a single oral dose of 0.3 mg/rat (150 kBq/rat) on gestational day 17 (GD17), GD18 or GD19. All dams were sacrificed on GD20. The blood and selected tissue samples taken from mothers and fetuses 24 h, 48 h or 72 h after exposure were evaluated for the distribution of HxCN. Results Maximum concentrations of HxCN in pregnant rats were found in the liver and adipose tissue. Relatively high levels of HxCN were also reported in the spleen, ovaries, adrenal glands and uterus, as well as in the sciatic nerve, brain and kidneys. Hexachloronaphthalene penetrates through the blood-brain barrier (BBB), as evidenced by twice the concentration in the brain compared to the blood concentration, and through the placental barrier, as indicated by the level of maternal-fetal compartment (placenta, amniotic fluid, litter). Among the examined fetal tissues, the highest levels of HxCN were found in the kidneys and in the brain. The concentrations in these organs were higher than that found in the maternal blood. Conclusions This paper is the first to detail the concentrations of HxCN in the maternal tissues and the transplacental transfer of the tested compound to the fetuses. The exposure of pregnant rats to HxCN results in its accumulation in the maternal liver, fat tissue, reproductive and nervous system, and particularly in the fetal brain. This demonstrates both the effective absorption and significant systemic accumulation which could lead to negative health implications. Int J Occup Med Environ Health 2018;31(5):685–69