Evaluation and comparison of DNA alkylation and oxidative damage in e-cigarette and heated tobacco users.

OBJECTIVES: This study, aimed to determine and compare DNA damage in e-cigarette and HTP (IQOS) users by assessing DNA-adducts, which are biomarkers of various DNA alkylation and oxidation. METHODS: For the evaluation of DNA alkylation, N3-Ethyladenine (N3-EtA) and N3-Methyladenine (N3-MeA) adducts were used. DNA oxidation was assessed using, 8-hydroxy-2'-deoxyguanosine(8-OHdG). The urinary cotinine, N3-MeA, N3-EtA, and 8-OHdG concentrations of the cigarette smokers (n:39), e-cigarette users (n:28), IQOS users (n:20), passive smokers (n:32), and nonsmokers(n:41) who lived Ankara, Turkiye were determined using, liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: In light of the detected 8-OHdG levels, e-cigarette (3.19 ng/g creatinine) and IQOS (4.38 ng/g creatinine) users had higher oxidative DNA damage than healthy nonsmokers (2.51 ng/g creatinine). Alkylated DNA-adducts were identified in the urine of e-cigarette (N3-MeA: 3.92 ng/g creatinine; N3-EtA: 0.23 ng/g creatinine) and IQOS (N3-MeA: 7.54 ng/g creatinine; N3-EtA: 0.29 ng/g creatinine) users. In the generation of N3-MeA adducts, a significant difference was found between IQOS users and e-cigarette users (p < 0.05). Also, DNA alkylation in flavored e-cigarette users (N3-MeA: 4.51 ng/g creatinine; N3-EtA: 0.27 ng/g creatinine) was higher than in non-flavored e-cigarette users (N3-MeA: 2.27 ng/g creatinine; N3-EtA: 0.06 ng/g creatinine). The highest cotinine levels were found in cigarette smokers (16.1316 ng/g creatinine). No significant difference was found when e-cigarette (1163.02 ng/g creatinine) and IQOS smokers were compared (1088.3 ng/g creatinine). CONCLUSION: People who use e-cigarettes and IQOS may be at higher risk of genotoxicity than those who do not use and are not exposed to any tobacco products. Furthermore, the usage of flavoring additives in e-cigarettes contributed to additional genotoxic damage risks.

Assessment of Preschool Children's Exposure Levels to Organophosphate and Pyrethroid Pesticide: A Human Biomonitoring Study in Two Turkish Provinces.

Pesticides are products developed to prevent, destroy, repel or control certain forms of plant or animal life that are considered to be pests. However, now they are one of the critical risk factors threatening the environment, and they create a significant threat to the health of children. Organophosphate (OP) and pyrethroid (PYR) pesticides are widely used in Turkey as well as all over the world. The main focus of this presented study was to analyze the OP and PYR exposure levels in urine samples obtained from 3- to 6-year-old Turkish preschool children who live in the Ankara (n:132) and Mersin (n:54) provinces. In order to measure the concentrations of three nonspecific metabolites of PYR insecticides and four nonspecific and one specific metabolite of OPs, liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses were performed. The nonspecific PYR metabolite 3-phenoxybenzoic acid (3-PBA) found in 87.1% of samples (n = 162) and the specific OP metabolite 3,5,6-trichloro-2-pyridinol (TCPY) found in 60.2% of samples (n = 112) were the most frequently detected metabolites in all urine samples. The mean concentrations of 3-PBA and TCPY were 0.38 ± 0.8 and 0.11 ± 0.43 ng/g creatinine, respectively. Although due to the large individual variation no statistically significant differences were found between 3-PBA (p = 0.9969) and TCPY (p = 0.6558) urine levels in the two provinces, significant exposure differences were determined both between provinces and within the province in terms of gender. Risk assessment strategies performed in light of our findings do not disclose any proof of a possible health problems related to analyzed pesticide exposure in Turkish children.

Establishment of rapid, sensitive, and quantitative liquid chromatography-electrospray ionization-tandem mass spectrometry method coupled with liquid-liquid extraction for measurement of urinary bisphenol A, 4-t-octylphenol, and 4-nonylphenol.

RATIONALE: Bisphenol A (BPA), 4-t-octylphenol (4-t-OP), and 4-nonylphenol (4-NP) are ubiquitous manufactured chemicals classified as endocrine disruptors. Now these substances are prevalent and found in a wide range of biological and environmental matrices globally. Acting as xenoestrogens, their target is to bind estrogen receptors and compete against natural hormones. Thus, there is an increasing concern on their negative health consequences. METHODS: A rapid, sensitive, and robust method was established, validated, and used for the trace analysis of BPA, 4-t-OP, and 4-NP in human urine using liquid chromatography-electrospray ionization-tandem mass spectrometry. RESULTS: The linear ranges for BPA, 4-t-OP, and 4-NP were 5.0-500 ng/mL. The correlation coefficient was higher than 0.996. The limit of detection and limit of quantitation for the compounds were 0.001, 0.007, and 0.005 ng/mL and 0.005, 0.023, and 0.180 ng/mL, respectively. The recoveries were as follows: 99.539%-108.557%, 97.780%-110.768%, and 99.694%-106.908% for BPA, 4-NP, and 4-t-OP respectively, with relative standard deviation <8.26%. CONCLUSIONS: The established method was also applied effectively for the determination of BPA, 4-t-OP, and 4-NP levels in 15 human urine samples. This method was specifically developed for easy and precise analysis of BPA, 4-t-OP, and 4-NP in human urine. The method developed has been shown to be accurate, precise, and sensitive.

The role of DENND1A and CYP19A1 gene variants in individual susceptibility to obesity in Turkish population-a preliminary study.

Single nucleotide polymorphisms (SNPs), the most common genetic variations in human genome, can manage the predisposition of certain complex diseases or situations such as obesity. Genetic polymorphisms also play an important role as they can impact a population's susceptibility to being overweight or obese and developing related chronic complications such as hypertension, coronary heart disease, diabetes and cancer. The present study comprised of 193 unrelated healthy volunteers (120 females and 73 males) with Turkish origin. Only female adolescents (n = 110) were divided into 2 categories according to their BMI values as overweight (BMI ≥ 25) and normal (18.5 < BMI < 25) according to WHO classification. Genomic DNA was isolated from venous blood samples and genotyping of DENND1A rs10818854 and CYP19A1 rs2414096 variants was performed on Roche Light Cycler 2.0 Real-Time PCR platform. Serum hormone levels were analyzed by Electrochemiluminescent Immunoassay (ECLIA; Roche diagnostics). The genotype distributions were consistent with the Hardy-Weinberg equilibrium for both SNPs in the studied population (p > 0.05). The genotype distribution of DENND1A rs10818854 was determined for the first time in Turkish population and the variant allele frequency was found as 0.095. According to reduced sex hormone-binding globulin levels and increased free androgen index in the present study, obesity was linked with hyperandrogenism in female subjects. Both polymorphisms were investigated as potential genetic susceptibility markers for obesity and neither DENND1A nor CYP19A1 showed any associations.

Evaluation of the endocrine-disrupting effects of homosalate (HMS) and 2-ethylhexyl 4-dimethylaminobenzoate (OD-PABA) in rat pups during the prenatal, lactation, and early postnatal periods.

Homosalate (HMS) and 2-ethylhexyl 4-dimethylaminobenzoate (OD-PABA) are ultraviolet filters. We aimed to investigate the effects of dermal exposure to HMS and OD-PABA during the prenatal, lactation, and early infancy periods on pubertal development and thyroid function in male and female rats. The thyroid glands, uteri, testes, prostate glands, and seminal vesicles were excised and weighed, the reproductive organs were analyzed histologically, and the serum hormone levels were measured. In the prenatal period, the thyroxine (T4) levels increased in the female rats in the exposed groups ( p < 0.05); the thyroid weights, reproductive organ weights, and gonadal hormone levels were not altered. In males, the testosterone levels decreased ( p < 0.05), but the thyroid weights, T4 levels, prostate, and testis weights were not changed. In the lactation period, the weights of the thyroid glands increased in the exposed female groups ( p < 0.05), but the T4, gonadal hormone levels, and reproductive organ weights were not changed. In the males, the thyroid gland weights, T4 levels, reproductive organ weights, and gonadal hormone levels were not changed. During infancy, the thyroid gland weights increased in the female rats in the exposed groups ( p < 0.05), but the T4 levels, gonadal hormone levels, and reproductive organ weights were not affected. In the male rats in the exposed groups, the T4 levels were increased ( p < 0.05), but the thyroid and reproductive organ weights, gonadal hormone levels were not affected. Organ histopathology was not affected in all groups. HMS and OD-PABA do not have endocrine disruptor effects on thyroid function and the pubertal development of female and male rats.

An investigation of the mutagenic activity of salamide - a major impurity of hydrochlorothiazide.

Hydrochlorothiazide is a widely used antihypertensive agent and one of its major impurities, salamide (4-amino-6-chlorobenzene-1,3-disulphonamide), has a chemical structure containing a primary amino group, a functional group that has previously been reported to be associated with carcinogenic activity. It is known that hydrochlorothiazide purity is a challenging problem for the pharmaceutical industry. As there were no prior mutagenicity data for the impurity salamide, the aim was to investigate its mutagenicity in this study. Salamide was tested for mutagenic potential in Salmonella typhimurium TA98, TA100, TA 1535, TA 1537, and E. coli WP2 uvrA + E. coli WP2 [pKM101] strains at six different concentrations, the highest concentration being the 5000 µg/plate. In both the presence and absence of the metabolic activation system, no mutagenic activity was observed. Results indicated that salamide should be classified as an ordinary impurity and controlled according to Q3A(R2) and Q3B(R2) guidelines.

Urinary cotinine levels of electronic cigarette (e-cigarette) users.

The popularity of electronic cigarettes (e-cigarettes) is rapidly increasing in many countries. These devices are designed to imitate regular cigarettes, delivering nicotine via inhalation without combusting tobacco but currently, there is a lack of scientific evidence on the presence or absence of nicotine exposure. Such research relies on evidence from e-cigarette users urine samples. In this study, we aimed to determine the levels and compare the amount of nicotine to which e-cigarette users, cigarette smokers and passive smokers are exposed. Therefore, urine samples were collected from e-cigarette users, cigarette smokers, passive smokers, and healthy nonsmokers. The urinary cotinine levels of the subjects were determined using gas chromatography-mass spectrometry. The mean (±SD) urinary cotinine levels were determined as 1755 ± 1848 ng/g creatinine for 32 e-cigarette users, 1720 ± 1335 ng/g creatinine for 33 cigarette smokers and 81.42 ± 97.90 ng/g creatinine for 33 passive smokers. A significant difference has been found between cotinine levels of e-cigarette users and passive smokers (p < 0.05). There were no statistically significant differences between e-cigarette users and cigarette smokers (p > 0.05). This is a seminal study to demonstrate the e-cigarette users are exposed to nicotine as much as cigarette smokers.

Blood levels of polychlorinated biphenlys and organochlorinated pesticides in women from Istanbul, Turkey.

The human body is not a chemically uncontaminated system. Every simple action that humans undertake, such as drinking water, eating, nursing, and even breathing air, puts the system under environmental xenobiotic exposure stress. Environmental chemicals have been shown to produce unwanted effects on health and remove the right to healthy living, starting from the first encounter in utero to geriatrics, throughout the lifespan. Organochlorine pesticides (OCPs) and polychlorinated biphenyl (PCB) levels, important members of the persistent organic pollutants (POPs), have been detected before in human breast milk and also in the adipose tissue of women from different regions of Turkey; however, there was no information about the blood levels of these chemicals. This study generated the first information that evaluates OCP and PCB contamination levels in the blood of the women living in Turkey. The current study measured the blood concentrations of OCPs and PCBs in 58 healthy women (age 20-41 years; mean age 28 years) who were living in Istanbul, Turkey, in the years 2010-2012. Samples were analyzed for 29 OCPs and 18 PCB congeners using high-resolution gas chromatography/high-resolution mass spectrometry (HRGC/HRMS). PCB 153 was the predominant congener (643.2 pg/g lipid), followed by PCB 138 and PCB 180. 4,4'-DDE (24872.8 pg/g lipid) was the most common organochlorinated pesticide contaminant in studied blood samples. Results for analyzed chlorinated compounds were as follows: ∑PCB 2682 ± 3300 pg/g lipid; ∑DDT 25,938 ± 28,644 pg/g lipid; and ∑HCH 2930 ± 2222 pg/g lipid, respectively. The mean concentration of ∑WHOPCB-TEQ was 0.037 pg/g on a lipid basis. This information will be important base data during the assessment of the general health concerns of women, as well as for studies about how endocrine disruptors affect humans for forthcoming studies.

Development and validation of an LC-MS/MS method for simultaneous quantitative analysis of free and conjugated bisphenol A in human urine.

Bisphenol A (BPA) is an environmental endocrine-disrupting chemicals that is widely used in common consumer products. There is an increasing concern regarding human exposure to BPA owing to the potential adverse effects associated with its estrogenic activity. For assessing environmental exposure to BPA, it is essential to have a sensitive, accurate and selective analytical method, especially one that can detect low BPA levels in complex sample matrices. In this study, we developed and validated an accurate, sensitive, and robust liquid chromatography-tandem mass spectrometry method for simultaneous quantification of free BPA and BPA ß-d-glucuronide (BPA-gluc) concentrations in human urine with only a single injection. Calibration curves were linear over a concentration range of 1-100 ng/mL for BPA and 10-1000 ng/mL for BPA-gluc. The levels of the analytes were determined quantitatively with HPLC/ESI-MS/MS by using negative electrospray ionization in the select ion monitoring mode and a pentaflouraphenyl propyl column. The validated method was applied to the analysis of spot urine specimens collected from randomly selected healthy human subjects.

CombiSimilarity, an innovative method to compare environmental and health data sets with different attribute sizes example: eighteen Organochlorine Pesticides in soil and human breast milk samples.

Human health and the health of the environment have entwined. In this paper we underpin this position by presenting a modeling approach named CombiSimilarity, which has been developed by the first author in the software tool PyHasse comprising a wide variety of partial ordering tools. A case study of 18 Organochlorine Pesticides (OCPs) detected in soil as well as in human breast milk samples in the Taurus Mountains in Turkey is carried out. Seven soil samples and 44 breast milk samples were measured. We seek to answer the question whether the contamination pattern in breast milk is associated with the contamination pattern in soil by studying the mutual quantitative relationships of the chemicals involved. We could demonstrate that there is a similarity with respect to the concentration profiles between the soil and breast milk pollution. Therefore the hypothesis may be formulated that the concentrations of chemicals in the milk samples are strongly related to the soil contamination. This supports the concept that soil could be a surrogate for human exposure at background locations.

Determination of urinary levels of Bisphenol A in a Turkish population.

Bisphenol A (BPA) is one of the environmental endocrine disrupting chemicals that is widely used in common consumer products. The aim of this study was to report the total urinary BPA concentrations (free plus conjugated) in 200 urine samples (children: 57; male: 74; female: 69) obtained from residents of a Mediterranean city, Mersin. Analyses were performed by high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) and for assessing environmental exposure to free BPA and its major metabolite bisphenol A glucuronide (BPAG) in human urine were determinated. Our results indicated that the free BPA and BPAG concentrations were in the range of 0.06-0.99 µg/g creatinine and 0.24-615 µg/g creatinine, respectively. No statistically significant difference obtained in BPA concentrations between genders (male and female) or domicile of residence (rural and urban) (p > 0.05). In our study, the mean level of detected free BPA was 0.46 µg/g creatinine in the urban area and 0.37 µg/g creatinine in the rural area. The average amount of BPAG was 60.56 µg/g creatinine in the urban area and 30.28 µg/g creatinine in the rural area. The data demonstrate that determined amount of total BPA in the present study is lower than the results of similar studies conducted in developed countries. There is no data about the levels of BPA in humans and environment in Turkey. Because of this reason, present study is very important since it is the first study in Turkey which determined the concentrations of free BPA and total BPA in human.

Evaluation of organochlorine pesticides in breast milk samples in Turkey applying features of the partial order technique.

Exposure data to organochlorine pesticides (OCPs) of mothers' breast milk samples were measured in different locations in the Taurus Mountains/Turkey. Villages at five altitudes were looked upon. The data analysis method applied is the Hasse diagram technique, based on Discrete Mathematics. For each of the five regions, one Hasse diagram was calculated and showed the same maximal object, namely, p-p'-Dichlorodiphenyldichloroethane (DDE). In a further data investigation step, we performed the similarity analyses of the locations in order to quantify the similarities and incomparabilities. It was revealed that no correlation exists between most altitudes and the pattern of contamination of breast milk samples. The two lowest situated areas, Sahil at sea level and Ciftlikköy at 121 m above sea level were similar. We reduced the datasets by applying the interval analysis followed by similarity analyses. We observed that endrin (END1), mirex (MIRE), and pentachlorobenzene (PECB) reduce most severely the similarity.

Biomonitoring of bisphenol A, 4-nonylphenol, and 4-t-octylphenol in Turkish population: exposure and risk assessment.

Biomonitoring studies are important tools to understand the effects of endocrine-disrupting compounds on human health. Up to now, there have been no biomonitoring and risk assessment studies conducted in Turkish population in which urinary bisphenol A (BPA), 4-nonylphenol (4-NP), and 4-t-octylphenol (4-t-OP) levels were measured simultaneously. The aim of this study is to measure urinary BPA, 4-NP, and 4-t-OP on Turkish population and conduct a risk assessment using urinary levels of chemicals of interest. During the study, liquid chromatography with tandem mass spectrometry (LC-MS/MS) was used to measure urinary levels of above-mentioned chemicals, and human biomonitoring was used as a risk assessment tool in 103 volunteers, living in Mersin Region, Turkey. Urinary BPA, 4-NP, and 4-t-OP were founded as 0.0079 µg/g creatinine, 0.0177 µg/g creatinine, and 0.0114 µg/g creatinine, respectively. The obtained estimated daily intakes (EDIs) were calculated as 0.095 µg/kg bw/day, 0.041 µg/kg bw/day, and 0.091 µg/kg bw/day, for BPA, 4-NP, and 4-t-OP, respectively. In conclusion, although no potential health risk due to BPA and 4-NP exposure was observed, there might be health risks associated with 4-t-OP exposure in the Turkish population.

An in vivo assessment of the genotoxic potential of bisphenol A and 4-tert-octylphenol in rats.

Bisphenol A (BPA) and octylphenol (OP) are industrial chemicals used in the manufacture of polycarbonate plastics, epoxy resins, and non-ionic surfactants. In the present study, we investigated the possible in vivo genotoxic effects of these compounds in rats using single-cell gel electrophoresis, the so-called comet assay. Adult male Wistar albino rats were divided randomly into six groups as follows: BPA125 (received 125 mg/kg bw BPA; n = 6), OP125 (received 125 mg/kg bw OP; n = 6), BPA250 (received 250 mg/kg BPA; n = 6), OP250 (received 250 mg/kg bw OP; n = 6), control (n = 5), and MMS (positive control group that received methyl methanesulfonate; n = 3). Both BPA and OP were orally administrated for 4 weeks. Controls were orally inoculated with corn oil for 4 weeks as well. Comet parameters including tail length and tail moment were evaluated for possible genotoxic effects. There were no significant differences in the OP125 and in the BPA125 compared with the control group, regarding tail length and tail moment (P > 0.05). However, there were significant differences in the OP250 and in the BPA250 compared with the control group, regarding tail length and tail moment (P < 0.05 and P < 0.01, respectively). The genotoxic potential of BPA and OP was investigated in vivo; there is a need for further studies exploring further mechanisms of the genotoxic potential of these chemicals in vivo.

Evaluation of DNA damage in common carp (Cyprinus carpio L.) by comet assay for determination of possible pollution in Lake Mogan (Ankara).

Contamination of the aquatic environment with various concentrations of pollutants results in unexpected threats to humans and wildlife. The consequences of exposure and metabolism of pollutants/xenobiotics, especially carcinogens and mutagens, can be suitably assessed by investigating severe events, such as DNA damage; for example, DNA adducts and DNA strand breaks. One of the commonly used techniques to detect DNA damage in aquatic organisms is single-cell gel electrophoresis (comet assay). This study was carried out using Cyprinus carpio in order to identify the possible pollution in Lake Mogan, near Ankara, Turkey, where the city's sewer system and pesticides used in agriculture are believed to be the common causes of pollution. From the comet assay, the tail length (micrometer), tail intensity (%), and tail moment values of fish caught from Lake Mogan were found to be 31.10 ± 10.39, 7.77 ± 4.51, 1.50 ± 1.48, respectively, whereas for clean reference sites they were found to be 22.80 ± 1.08, 3.47 ± 1.59, 0.40 ± 0.51, respectively. The values are statistically different from each other (p < 0.0001, p < 0.0001, and p = 0.0013, respectively). These results indicate that Lake Mogan may be polluted with substances that have genotoxic effects and constitute an early warning for the lake system. Further detailed research is needed to establish the source of the pollution and the chemicals responsible.

Polychlorinated biphenyl and organochlorine pesticide levels in human breast milk from the Mediterranean city Antalya, Turkey.

In this study, organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) levels were determined in 100 human milk samples from the city of Antalya. The levels of seven major PCB congeners; 28, 52, 101, 118, 138, 153, 180 and nine OCPs, α-HCH, ß-HCH, γ-HCH, HCB, heptachlor epoxide, p.p'-DDT, p,p'-DDE, endosulfan-α and endosulfan-ß were determined by gas chromatography with ECD detection. The levels of analyzed compounds were as follows: ΣPCBs 27.46 ± 11.58, ΣDDT 1,407 ± 123, and ΣBHC 160 ± 490 ng/g lipid wt.basis. PCB 153 and p,p'-DDE were the dominant contaminants. The results have been discussed and compared with similar studies from other regions of Turkey.

Determination of 7-ethoxyresorufin-o-deethylase (EROD) induction in leaping mullet (Liza saliens) from the highly contaminated Aliaga Bay, Turkey.

Pollution of the aquatic environment is a global concern owing to the devastating effects of contaminants whose levels are growing at an alarming rate, and it has become a major threat for marine organisms, as well as to humans as consumers. This study has been carried out on leaping mullet obtained from Aliaga Bay, which is located on the west coast of the Aegean Sea near Izmir and hosts the world's fifth largest shipyard, plus a broad range of industrial activities, including an oil refinery and a paper factory. The waste from these industries, combined with municipal sewer discharges, is the main cause of pollution in this region. There is no national documentation or research on the determination of pollution resulting from the industrial activities in this area. In the present study, the degree of induction of CYP4501A-associated 7-ethoxyresorufin O-deethylase (EROD) activity and immunochemical detection of CYP1A1 in the liver of leaping mullet (Lisa saliens) were used as biomarkers for the assessment of polycyclic aromatic hydrocarbon (PAH)-type organic pollutants in Aliaga Bay. Mullet caught from different locations of the bay had approximately 52 times more EROD activity than the feral fish sampled from a clean reference site near Foca, Izmir. The results of this study indicate that Aliaga Bay is highly contaminated with PAH-type organic pollutants.

Determination of organochlorine pesticide and polychlorinated biphenyl levels in adipose tissue of infertile men.

During the recent two decades, a remarkable drop in fertility rates has been noticed almost all over the world. A series of studies have showed that environmental factors had the primary role causing the observed adverse trends in the male reproductive health problems. Especially chlorinated hydrocarbons, for instance polychlorinated biphenyls (PCB) and pesticides, could mimic or antagonize the effects of steroid hormones, like estrogens and androgens and possibly interfering with male reproductive capacity. Organochlorine pesticides (OCPs) (i.e. p.p'-DDT, endosulfan...) and PCBs are widespread used chemicals in agriculture and industry for different purposes all over the world. Although direct evidence is lacking, theoretical considerations and epidemiological evidence implicate these compounds as potential hazards to human and wildlife reproductive health. For this purpose, in this study adipose tissue samples have provided from healthy males which were diagnosed as infertile men living in Ankara, Turkey at least for 5 years. Residual levels of OCPs (alpha-BHC, beta-BHC, gamma-BHC, HCB, Endosulfan I, II, p,p'-DDE, and p,p'-DDT) and seven major persistent PCB congeners (PCB 28, 52, 101, 118, 138, 153, and 180) were measured in 25 infertile men and 21 healthy men's adipose tissue samples by GC-ECD. Levels of OCPs and PCBs in adipose tissue of infertile men compared with those provided from controls. When the concentrations of each of the OCP were compared between the fertile and infertile groups, no statistical significance was obtained. Concentrations of each of the PCB congeners were compared between the fertile and infertile groups, no statistical significance was obtained (p > 0.05), except for 2,2',5,5'-Tetrachlorobiphenyl (PCB 52) (p = 0.032) and 2,2',3,4,4',5,5'-heptachlorobiphenyl (PCB 180) (p = 0.017).

Psychoactive Bath Salts and Neurotoxicity Risk.

Synthetic cathinones are new designer drugs that possess hallucinogenic and psychostimulant properties, and are designed to mimic the effects of illegal substances such as cocaine, amphetamines, and 3.4-methylenedioxymethamphetamine (ecstasy) and to produce rewarding effects, circumventing existing laws and penalties. Synthetic cathinones, also referred to as 'bath salts', have become popular particularly among young people since the mid-2000s. Similar to other psychomotor stimulants, synthetic cathinones have the potential to increase monoamine concentration in the synaptic cleft by targeting the plasma membrane transporters of dopamine, norepinephrine, and serotonin. Because of their structural similarities to amphetamines, it has been suggested that synthetic cathinones may have a neurotoxicity profile similar to that of their amphetamine congeners. Therefore, it has been hypothesized that synthetic cathinones may induce neurotoxicity on monoamine nerve endings in the striatum, hippocampus, and cortex. To date, with regard to synthetic cathinone neurotoxicity, parameters such as monoamine depletion, biosynthetic enzyme inhibition, cytotoxicity, generation of reactive oxygen species, pro-oxidation status, and the ability to induce neuroinflammation were investigated in both in vitro and in vivo experimental studies. Compared with amphetamines, synthetic cathinones appear to have more moderate effects than their amphetamine congeners in terms of neurotoxic effects. However, many synthetic cathinone users take these substances simultaneously with other substances such as benzodiazepines, amphetamines, ecstasy, tetrahydrocannabinol, and ethanol and this abuse can modify their neurotoxic effects. Hence, it is important to understand the underlying mechanism of early neurotoxic effects in case of polysubstance use. In this review, we aimed to present up-to-date information on the abuse potential of synthetic cathinones, their legal status, mechanism of action, and particularly their neurotoxic effects.

Assessment of Bisphenol A Levels in Preschool Children: Results of a Human Biomonitoring Study in Ankara, Turkey

Objective: There is general concern regarding environmental chemical exposure and the impact it may have on human health. This is particularly important for vulnerable populations such as infants and children during critical periods of development. Bisphenol A (BPA) is an endocrine disrupting chemical used worldwide over the last 30 years in many consumer products. Evidence points to widespread human exposure to BPA. The aim of this study was to evaluate the exposure of Turkish preschool children to BPA. Methods: This study was conducted as a preliminary investigation of BPA in urine, collected from 3-6 year old children living in Ankara. After spot urine samples were taken from preschool children, free BPA, ß-D-glucuronide and total BPA were determined using high-performance liquid chromatography tandem mass spectrometry and adjusted by creatinine concentration. Results: Preschool children from Ankara (n=125; males n=70, females n=55; mean age: 4.50±1.26) were recruited. BPA was detected in 76.8% of children from Ankara city, with urinary concentrations ranging from < limit of quantification to 18.36 µg/g creatinine. Total BPA levels were not statistically different between boys (1.26 µg/g creatinine) and girls (2.24 µg/g creatinine) (p>0.05). Conclusion: This study is an important contribution to the limited information about childhood exposure to BPA. The estimated daily BPA intake in this study is substantially lower than the European Food Safety Authority derived tolerable daily intake of 4 µg/kg BW/day.