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Objectives 1-Methylnaphthalene (1-MN) is a constituent of polycyclic aromatic hydrocarbons, the chemicals that have become ubiquitous in the environment as result of natural and industrial process. This paper reports a study on the distribution and excretion of 1-MN in rats after single and repeated inhalation exposure to 1-MN vapor. Material and Methods Male Wistar rats were exposed to 1-MN vapor at nominal concentrations of 50 mg/m³ or 200 mg/m³ in the dynamic inhalation chambers (TSE Systems Head Nose Only Exposure) for 6 h (single exposure) or 5 days (6 h/day, repeated exposure). Blood, urine and tissue samples were collected during and after the exposure. Blood, urine and tissue concentrations of 1-MN were estimated by gas chromatography using the headspace technique. Results The elimination of 1-MN from blood followed an open 2-compartment model. The concentration in rat tissues was dependent on the magnitude and time of exposure. After repeated exposure, the concentration 1-MN in tissue decreased in comparison to single exposure. The elimination of 1-MN with urine after single and repeated exposure to 1-MN occurred mainly in the samples collected during the first day of collection. Conclusions 1-Methylnaphthalene was rapidly eliminated from the blood and tissues of animals exposed by inhalation to 1-MN. In repeated exposure, there was probably a significant increase of 1-MN metabolism in rats exposed to low and high 1-MN doses. Under conditions of repeated 1-MN exposure, no significant systemic 1-MN accumulation could be observed. Int J Occup Med Environ Health 2018;31(6):763–770
EN
ObjectivesThis paper reports on the trend of the stressogenic stimulus caused by a repeated exposure to 1-methylnaphthalene (1-MN) vapors at the nominal concentrations of 0 mg/m3 (the control restrainer), 50 mg/m3 or 200 mg/m3 in the nose-only inhalation system, by analyzing the serum corticosterone (CORT) levels in rats.Material and MethodsThree groups of rats were exposed in restrainers to 1-MN vapors at the nominal concentrations of 0 mg/m3, 50 mg/m3 or 200 mg/m3 for 5 days. One control group of animals spent all the time during the experiment in an individually ventilated plastic cage. The serum CORT concentrations were determined in all 4 groups of the rats. The blood samples drawn from the tail vein were collected every day after termination of the 6-h exposure. On the fifth day, blood samples were collected 15 min, 30 min, 45 min, 1 h, and 3 h after termination of the 6-h exposure.ResultsOn the fifth day of the study, no statistically significant changes in body weights between all groups of animals were found. After 5 days of the observation, increased food intake in the control groups was noted. Significantly higher CORT concentrations in the rats exposed to 1-MN at 200 mg/m3 and in the animals from the control restrainer were found, comparing to the animals exposed to 1-MN at 50 mg/m3 and the animals from the control cage.ConclusionsThe application of 6-h restraining induced high concentrations of the stress hormone, CORT, in the blood of rats. The short-term exposure of rats to 1-MN non-linearly reduced the restraint stress measured with CORT concentration.
EN
Objectives The aim of the study has been to explore hemimellitene distribution in blood, liver, lung and kidney as well as toxicokinetics of its elimination from blood of rats after single and repeated inhalation exposure to this compound. Tissue distribution and excretion with urine of 2-dimethylbenzoic acids (2,3-DMBA and 2,6-DMBA) were also evaluated. Material and Methods Male outbred IMP:WIST rats were used in the experiment. The animals were exposed to hemimellitene vapors at the nominal concentration of 25 ppm, 100 ppm, and 250 ppm in the dynamic inhalation chambers for 6 h for single exposure purpose and for 4 weeks (6 h/day for 5 day/week) for repeated exposure purposes. Results Significantly lower concentrations of hemimellitene were detected in the blood and tissues of animals after repeated inhalation exposure of animals to hemimellitene vapors, which points to reduced retention of the chemical in the lungs of the experimental rats. The trend of hemimellitene elimination from the blood depended solely on exposure intensity, irrespective of exposure time, both after single and repeated exposure. As regards the 2 determined hemimellitene metabolites, the major trend of the metabolic transformation involved formation of 2,3-DMBA. Conclusions The significantly higher urinary 2,3-DMBA concentration after repeated exposure shows that hemimellitene induces enzymatic processes in the rat.
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Objectives The study has aimed at investigating the subjective assessment of an individual’s health status and comparing the prevalence of selected work-related symptoms among nail technicians occupationally exposed to volatile organic compounds (VOCs) to the one among control subjects. Associations between occupational exposure to VOCs and the incidence of adverse health effects were also analyzed. Material and Methods The study involved 145 female nail technicians and 152 control subjects. Data on the prevalence of adverse health effects was collected using the researcher- made questionnaire and then analyzed by means of survival analysis methods. Results Only 22% of nail technicians as compared to 45% of control subjects described their current health status as “excellent” or “very good” (odds ratio (OR) = 0.4, 95% confidence interval (CI): 0.2–0.6, p < 0.00005). In general, 61% of nail technicians confirmed to have experienced any out of all symptoms considered in the study since the commencement of the job, which was significantly higher as compared to 17% of control subjects (adjusted OR = 2.8, 95% CI: 2.1–3.7, p < 0.0001). Estimated median length of the employment period free of investigated symptoms was significantly shorter among nail technicians as compared to controls (12 years vs. 33 years, p < 0.0001), consistent with almost 4-times increased hazard of the occurrence of such symptoms among the technicians (hazard ratio (HR) = 3.9, 95% CI: 2.7–5.7, p < 0.0001). Cox proportional hazard regression modeling revealed almost 5-times increased hazard of the occurrence of any symptoms among nail technicians exposed to higher levels of the mixture of VOCs as compared to those exposed to lower levels (HR = 4.9, 95% CI: 1–24.1, p = 0.05). Conclusions All outcomes combined together indicate that nail technicians are subject to faster health deterioration, which may be assumed to be caused by occupational exposure to low levels of VOCs. Int J Occup Med Environ Health 2017;30(3):469–483
EN
Objectives: Exposure to various stressors is known to result in sensitization to psychostimulants, a state related to the psychostimulant dependence and addiction. It has been shown in some studies that the rise in corticosterone (CORT) concentration is indispensable for both the induction and the expression of behavioral sensitization. Therefore, it might be suspected that behavioral hyposensitivity to amphetamine (AMPH) is somehow related to a reduced CORT response to the psychostimulant subsequent to the chlorphenvinphos (CVP) intoxication. Materials and Methods: The male adult Wistar rats received single i.p. injections of CVP at the doses 0.5, 1.0 or 3.0 mg/kg b.w., or pure corn oil. CORT concentration was determined in samples of blood drawn from the tail vein before and then 30, 60, 180 min and 24 h after injection. The other rats were divided into two groups and tested, three weeks after the CVP injection for the effect of AMPH (0.5 mg/kg b.w. i.p.) on the serum CORT concentration. In addition, behavioral sensitivity to AMPH was assessed by measuring locomotor activity of the animals in an open-field. Results: 1) The stressor property of CVP was confirmed. The injection resulted in up to tenfold increase in the serum CORT concentration. The magnitude and duration of this response were dose-related. 2) Three weeks after the CVP exposure, the CORT response to AMPH was significantly increased. 3) The behavioral response to the psychostimulant, i.e. augmented locomotion, was significantly reduced compared to the control. Conclusions: The results confirm that CVP exposure causes behavioral hyposensitivity to AMPH. This effect, however, could not be ascribed to a diminished CORT response.
EN
Objectives: This paper presents toxic effects of 2-MN in laboratory animals under conditions of 4-week inhalation exposure to 2-methylnaphthalene (2-MN) vapors. Materials and Methods: Male Wistar rats were exposed to 2-MN vapors at a nominal concentration of 0, 2, 10 or 50 mg/m³ in dynamic inhalation chambers for 4 weeks (6 h/day, 5 days/week). After 4 weeks of inhalation exposure the animals were necropsied. Blood samples were collected and selected organs were weighted and prepared for histological examinations. Results: The effects of the increased levels of exposure to 2-MN experienced by the experimental rats were as follows: a) increasing γ-glutamylotransferase activity, b) stimulation of the hematopoietic system, c) lower cholesterol concentrations, d) higher number of goblet cells in lobar bronchi, e) hyperplasia of hepatic bile ducts. Conclusion: Four-week exposure of the animals to 2-MN at 2 mg/m³ proved to be the no-observed-adverse-effect-level (NOAEL), while 10 mg/m³ appeared to represent the lowest-observed-adverseeffect- level (LOAEL).
EN
Objectives The solvent, dimethylene glycol monobutyl ether (DGBE), is a component of latex paints, inks; it is used as a degreasing agent, industrial detergent. The aim of the study was evaluating the effects of DGBE administered by gavage on the estrous cycle and given with drinking water on fertility in rats and early development of their progeny. Materials and Methods Female rats were exposed to DGBE by gavage during 8 weeks at 250, 500 or 1000 mg/kg/day. Vaginal smears were collected during the exposure and 4 weeks after its cessation. Fertility studies were performed in male and female animals exposed to in drinking water. Males were exposed for 10 weeks and then mated with females exposed before mating, during pregnancy and lactation. Young animals were observed during 3 weeks after birth. Results DGBE does not cause disturbances of the menstrual cycle in females. Parameters used to assess the general toxicity indicate that males receiving DGBE in drinking water are more sensitive to this compound than females: significantly greater, dose-dependent relative spleen weight, significant decrease in hematological parameters from 8% to 15% depending on the dose, were observed. Clinical chemistry parameters (HDL-cholesterol, BUN) and some markers of oxidative stress differ between the exposed groups and the control one, but without adverse health effect. The microscopic examination of internal organs did not reveal morphological changes in male and female rats. Conclusion The results of our study on the impact of exposure to DGBE on fertility in rats indicate that the substance administered for 9–10 weeks to females and males at a limit dose of 1000 mg/kg did not impair fertility or viability of their offspring during the first three weeks of life.
EN
Objectives: Diisocyanates (DIC) are highly reactive, low-molecular-weight chemicals which are the leading cause of occupational asthma (OA). The aim of the study was to analyze certain aspects of the pathogenesis of allergic infl ammation in the airways induced by toluene diisocyanate (TDI) in an experimental model in mice. Materials and Methods: The experiment was carried out on 50 female BALB/cJ/Han/IMP mice, which were exposed by inhalation (intranasal and in the inhalation chamber) to toluene diisocyanate (2,4-TDI). After the experiment, the bronchoalveolar lavage fluid (BALF) was collected from the animals, and the composition of the induced infl ammatory cells, and the concentrations of certain cytokines (IL-4, IL-5, TNF-α) were evaluated. Results: The total number of cells in BALF of the examined group of mice was signifi cantly higher compared to the control mice. There was also a signifi cant increase in neutrophils and eosinophils in the study group compared to the controls. The number of lymphocytes and macrophages did not differ signifi cantly between the two groups. A statistically signifi cant increase in the level of TNF-α was shown to occur in the group exposed to toluene diisocyanate in comparison to the control group. The concentration of IL-4 increased in the study group, compared to the control one, but the differences did not reach the level of signifi cance, p > 0.05. Such difference was not observed for IL-5. Conclusions: We developed a murine model of TDI-induced asthma which caused the infl ux of infl ammatory cells like eosinophils and neutrophils in the bronchoalveolar lavage fl uid (BALF) in the TDI-treated mice. The increase of the concentration of some proinfl ammatory cytokines (TNF-α, IL-4) in BALF from the exposed mice was also observed.
EN
Background: Organophosphates are cholinesterase (ChE) inhibitors with worldwide use as insecticides. Stress response, evidenced by a dramatic and relatively long-lasting (several hours) rise in the plasma glucocorticoid concentration is an integral element of the organophosphate (OP) poisoning symptomatology. In rodents, corticosterone (CORT) is the main glucocorticoid. There are several reports suggesting a relationship between the stressor-induced rise in CORT concentraion (the CORT response) and the activity of the cerebral and peripheral ChE. Thus, it seems reasonable to presume that, in OP intoxication, the rise in plasma CORT concentration may somehow affect the magnitude of the OP-induced ChE inhibition. Metyrapone (MET) [2-methyl-1,2-di(pyridin-3-yl)propan-1-one] blocks CORT synthesis by inhibiting steoid 11β-hydroxylase, thereby preventing the CORT response. Chlorfenvinphos (CVP) [2-chloro-1-(2,4-dichlorophenyl) ethenyl diethyl phosphate] is an organophosphate insecticide still in use in some countries. Material and Methods: The purose of the present work was to compare the CVP-induced effects - the rise of the plasma CORT concentration and the reduction in ChE activity - in MET-treated and MET-untreated rats. Chlorfenvinphos was administered once at 0.0, 0.5, 1.0 and 3.0 mg/kg i.p. Metyrapone, at 100 mg/kg i.p., was administered five times, at 24-h intervals. The first MET dose was given two hours before CVP. Conclusion: The following was observed in the MET-treated rats: i) no rise in plasma CORT concentration after the CVP administration, ii) a reduced inhibition and a faster restitution of blood and brain ChE activities. The results suggest that MET treatment may confer significant protection against at least some effects of OP poisoning. The likely mechanism of the protective MET action has been discussed.
EN
Background: Benzalkonium chloride (BAC) is a quaternary ammonium compound (QAC) toxic to microorganisms. Inhalation is one of the major possible routes of human exposure to BAC. Materials and Methods: Experiments were performed on female Wistar rats. The rats were exposed to aerosol of BAC water solution at the target concentration of 0 (control group) and 35 mg/m³ for 5 days (6 h/day) and, after a 2-week interval, the animals were challenged (day 21) with BAC aerosol at the target concentration of 0 (control group) and 35 mg/m³ for 6 h. Results: Compared to the controls, the animals exposed to BAC aerosol were characterized by lower food intake and their body weight was significantly smaller. As regards BAC-exposed group, a significant increase was noted in relative lung mass, total protein concentration, and MIP-2 in BALF both directly after the termination of the exposure and 18 h afterwards. Significantly higher IL-6 and IgE concentrations in BALF and a decrease in the CC16 concentration in BALF were found in the exposed group immediately after the exposure. The leukocyte count in BALF was significantly higher in the animals exposed to BAC aerosol compared to the controls. In the lungs of rats exposed to BAC the following effects were observed: minimal perivascular, interstitial edema, focal aggregates of alveolar macrophages, interstitial mononuclear cell infiltrations, thickened alveolar septa and marginal lipoproteinosis. Conclusion: Inhalation of BAC induced a strong inflammatory response and a damage to the blood-air barrier. Reduced concentrations of CC16, which is an immunosuppressive and anti-inflammatory protein, in combination with increased IgE concentrations in BALF may be indicative of the immuno-inflammatory response in the animals exposed to BAC aerosol by inhalation. Histopathological examinations of tissue samples from the BAC-exposed rats revealed a number of pathological changes found only in the lungs.
EN
Objectives Welding processes that generate fumes containing toxic metals, such as hexavalent chromium (Cr(VI)), manganese, and nickel (Ni), have been implicated in lung injury, inflammation, and lung tumor promotion in animal models. Bronchiolar epithelium Clara cells/club cells, coordinate these inflammatory responses. Clara cells secretory protein (CC16) with ant-inflammatory role. Material and Methods The pulmonary toxicity of welding dust (WD) was assessed for Wistar rats exposed to 60 mg/m³ of respirable-size welding dust (mean diameter 1.17 μm for 1 and 2 weeks (6 h/day, 5 days/week)) or the aerosols of soluble form (SWD) in the nose-only exposure chambers. Additionally the effect of antiinflammatory betaine supplementation was assessed. Clara cells secretory protein, differential cell counts, total protein concentrations and cellular enzyme (lactate dehydrogenase – LDH) activities were determined in bronchoalveolar lavage fluid, and corticosterone and thiobarbituric acid reactive substances (TBARS) and prolactin concentrations were assessed in serum. Histopathology examination of lung, brain, liver, kidney, spleen was done. Additionally slices of brain and lung were exanimated in laser ablation inductively coupled plasma mass spectrometry. Results Both WD and SWD exposure evoked large bronchiolar infiltration shoved in histopathology examination. In this study, TBARS inversely correlated with a significant decrease of CC16 concentration that occurred after instillation of both WD and SWD indicating decreased anti- inflammatory potential in the lung. In WD exposed rats prolactin correlated with nuclear factor-kappa B (NF-κB), LDH, TBARS and serum levels Cr, Ni and inversely with c-Jun. In SWD exposed rats prolactin correlated with CC16 indicated effect of prolactin on the population of epithelial cells. Conclusions In the current study, deleterious effects of repeated inhalation stainless steel welding dust form on club (Clara) cell secretory protein (CC16) were demonstrated. Clara cells secretory protein relation with prolactin in exposed rats to welding dust were shown and explored whether the NF-κB and c-Jun/activator protein 1 related pathway was involved. Int J Occup Med Environ Health 2018;31(5):613–632
EN
Objectives 1-Methylnaphthalene (1-MN) is composed of 2 benzene rings and belongs to polycyclic aromatic hydrocarbons. The metabolism of 1-MN in laboratory animals and bacteria leads to the formation of 1-naphthoic acid (1-NA). Material and Methods In this study the distribution of 1-NA in lung, liver, spleen, kidney and urinary excretion of 1-NA in rats after single and repeated inhalation exposure to 1-MN vapors were investigated. The activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and cytochrome were measured of the rats. Genotoxic effects were evaluated with the in vitro micronucleus test on V79 hamster fibroblasts. Results The concentrations of 1-NA in the tissues of rats after single and repeated exposure to 1-MN were dependent on the exposure dose. High levels of 1-NA were found in kidneys of animals after the single and repeated exposure to 1-MN. With an increase of 1-MN dose, an increase in the activity of cytochrome P450 (CYP1A1 and CYP1A2) was observed in the liver of rats. Compared to control animals, significantly higher ALT activity was noted in serum of rats exposed to 1-MN. The micronuclei frequency in V79 cells exposed to 1-MN (in the range of analyzable concentrations; i.e., 5–25 μg/ml) did not differ significantly from the vehicle control, whereas urine extracts from rats exposed to 1-MN induced a significant increase in the frequency of micronuclei compared to urine extracts from the group of control animals. Conclusions Metabolism of 1-MN in rats after the inhalation exposure leading to 1-NA was mainly observed during the first day after the end of exposure. It is likely that 1-MN metabolites present in rat urine can induce the increased micronuclei frequency as was shown in V79 cells.
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