Mutagenic Risk Research Articles

The concentration of polycyclic aromatic hydrocarbons (PAHs) in mother milk: A global systematic review, meta-analysis and health risk assessment of infants

BackgroundBio-monitoring of polycyclic aromatic hydrocarbons (PAHs) contaminants in mother milk is essential to keep mothers and infants healthy against potential risks. The current study assesses the concentration of PAHs in mother milk through a meta-analytic and systematic review approach.MethodsAll the published studies up to December 2020 regarding the concentrations of various PAHs in mother milk were searched throughout major international databases such as PubMed, Scopus, and Web of Science. Moreover, the possible carcinogenic and mutagenic risks to infants were evaluated based on the BaP (benzo[a]pyrenee) equivalent dose.ResultsAccording to the results of 13 articles included among 936 retrieved studies, the lowest and highest concentration of PAHs was (0.125 ng/g) and (76.36 ng/g) related to benz(a)anthracenem and 1-methylnaphthalene, respectively. The highest (9.830 ng/g) and lowest (0.009 ng/g) concentration of PAHs was related to Mexico and Japan, respectively. Besides, carcinogenetic and mutagenic risk assessment of the PAHs indicated that risk pattern was different across countries. It can be concluded that the consumption of mother milk is safe and does not pose a risk due to the ingestion of PAHs to the health of infant consumers.

Occurrence and source apportionment of polycyclic aromatic hydrocarbons (PAHs) in dust of an emerging industrial city in Iran: implications for human health.

Polycyclic aromatic hydrocarbons (PAHs) bounded to street dust are a severe environmental and human health danger. This study provides preliminary information on the abundance of PAHs in street dust from Rafsanjan city, Iran, where industrial emissions are high and data are lacking. Seventy street dust samples were collected from streets with different traffic loads. The United States Environmental Protection Agency (USEPA) Standard Methods 8270D and 3550C were used for the measurement of PAHs using GC mass spectroscopy. The total concentration of PAHs was 1443 ng g-1, with a range of 1380-1550 ng g-1. Additionally, the concentration of carcinogenic PAHs (∑carcPAHs) ranged from 729.5 to 889.4 ng g-1, with a mean value of 798.1 ng g-1. Pyrene was the most abundant PAH, with an average concentration of 257 ng g-1. Source identification analyses showed that vehicle emissions along with incomplete combustion and petroleum were the main sources of PAHs. The ecological risk status of the studied area was moderate. Spatial distribution mapping revealed that the streets around the city center and oil company had higher PAH levels than the other sectors of Rafsanjan. The results indicated that dermal contact and ingestion of contaminated particles were the most important pathways compared to inhalation. The mean incremental lifetime cancer risk (ILCR) was 1.4 × 10-3 and 1.3 × 10-3 for children and adults, respectively. This implies potentially adverse health effects in exposed individuals. The mutagenic risk for both subpopulations was approximately 18 times greater than the one recommended by USEPA. Our findings suggest that children are subjected to a higher carcinogenic and mutagenic risk of PAHs, especially dibenzo[a,h]anthracene (DahA), bounded to street dust of Rafsanjan. Our study highlights the need for the development of emission monitoring and control scenarios.

Levels and risk assessments of polycyclic aromatic hydrocarbons in soil situated around unlined dumpsite in Okpunoeze, Nnewi, Nigeria

ABSTRACT Polycyclic aromatic hydrocarbons (PAHs) are organic pollutant found in the soil which can cause several health effects to human beings and the environment. The study was aimed at evaluating the concentration level of PAHs of soil located around an open/unlined dumpsite. 32 samples comprising of 16 samples each of upstream and downstream (control) were obtained in both seasons. The concentration of PAHs was ascertained using gas chromatography interfaced with a flame ionisation detector (FID). Toxic and mutagenic risk assessments were employed to evaluate the toxicity risk. The probability of cancer health risks was determined through dermal and ingestion routes. Molecular PAHs ratios were used to predict the potential sources. The PAHs concentrations in the upstream and downstream ranged from ND – 120.6 µg/kg and 0.03–7.08 µg/kg respectively. Total PAHs concentrations in the upstream and downstream ranged from 20.57–144.28 µg/kg and 11.43–18.84 µg/kg respectively. The upstream samples PAH concentrations were greater than the downstream site in both seasons. The PAH concentration in the wet season was greater than the dry season values, which was possibly due to leachate pollution. The four-ringed PAHs were the most prominent in the PAHs, while the six-ringed PAHs were the least dominant PAHs for both seasons. Benzo(a)pyrene values estimated from Ba and Ba were found to have possible chances of carcinogenic and mutagenic risks in the soil samples for both upstream and downstream locations. There were no chances of possible carcinogenic risks through ingestion and dermal exposure routes. The values of diagnostic ratios obtained confirmed that PAHs sources are predominantly from pyrolytic sources for upstream location. Downstream diagnostic ratios values had a slightly dominant petrogenic source than the pyrolytic sources.

Mutagenicity and genotoxicity of water boiled in aluminum pots of different duration of use using SOS chromotest and Ames fluctuation test.

Boiling water before drinking or using it for cooking is a general practice especially in areas where portable water is not readily available. However, boiling water in an aluminum pot could be a route of entry of heavy metals into humans. This study assessed the genotoxic and mutagenic potential of boiled water samples from aluminum pots of different duration of use using the SOS chromotest on Escherichia coli PQ37 and the Ames fluctuation test on Salmonella typhimurium strains TA98 and TA100, respectively. Three aluminum pots from the same manufacturer but of different years of use (6-year-old, 3-year-old, and new aluminum pots) were used for the experiment. Six selected heavy metals (Cadmium, Copper, Arsenic, Nickel, Lead, and Aluminum) were also analyzed in the samples using an Atomic Absorption Spectrophotometer (AAS Buck, Scientific model 210 VGP). Cadmium, Copper, Arsenic, Nickel, Lead, and Aluminum were present in all the test water samples at concentrations that were higher than the maximum limit allowable by standard regulatory organizations. The concentrations of these metals in the samples also increased as the duration of use of the aluminum pots increased. The results further showed that the water boiled in the three aluminum pots is mutagenic and genotoxic in both Ames fluctuation and SOS chromotests. The 6-year-old aluminum pot induced the highest mutagenicity and genotoxicity followed by the 3-year-old aluminum pot. The metals in the tested samples were believed to be responsible for the observed mutagenicity and genotoxicity in the microbial assays. The findings of this study revealed that cooking with Aluminum pots could lead to the leaching of heavy metals into food, and pose mutagenic and genotoxic risks to consumers.

Predicting genotoxicity of viral vectors for stem cell gene therapy using gene expression-based machine learning

Hematopoietic stem cell gene therapy is emerging as a promising therapeutic strategy for many diseases of the blood and immune system. However, several individuals who underwent gene therapy in different trials developed hematological malignancies caused by insertional mutagenesis. Preclinical assessment of vector safety remains challenging because there are few reliable assays to screen for potential insertional mutagenesis effects invitro. Here we demonstrate that genotoxic vectors induce a unique gene expression signature linked to stemness and oncogenesis in transduced murine hematopoietic stem and progenitor cells. Based on this finding, we developed the surrogate assay for genotoxicity assessment (SAGA). SAGA classifies integrating retroviral vectors using machine learning to detect this gene expression signature during the course of invitro immortalization. On a set of benchmark vectors with known genotoxic potential, SAGA achieved an accuracy of 90.9%. SAGA is more robust and sensitive and faster than previous assays and reliably predicts a mutagenic risk for vectors that led to leukemic severe adverse events in clinical trials. Our work provides a fast and robust tool for preclinical risk assessment of gene therapy vectors, potentially paving the way for safer gene therapy trials.

Mutagenicity risk prediction of PAH and derivative mixtures by in silico simulations oriented from CYP compound I-mediated metabolic activation

PAHs and their derivatives are the main sources of mutagenicity and carcinogenicity in airborne particular matter and cause serious public health and environmental problems. Risk assessment is challenging due to the mixed nature and deficiency of toxicity data of most PAHs and their derivatives. Cytochrome P450 enzymes (CYPs) play important roles in PAH-induced carcinogenicity via metabolic activation, and CYP conformations with compound I structures strongly influence metabolic sites and metabolite species. In this study, complexes of BaP with CYP1A1, CYP1B1 or CYP2C19 compound I were successfully simulated by QM/MM methods and verified by metabolic clearance, and the mutagenicity of chemicals was then predicted by the BaP-7,8-epoxide-related metabolic conformation fitness (MCF) approach, which was validated by Ames tests, showing satisfying accuracy (R2 = 0.46–0.66). Furthermore, a prediction model of the mutagenicity risk of PAH and derivative mixtures was established based on the relative potential factor (RPF) approach and the RPF calculated from the mathematical relationship between the minimum MCF (MCFmin) and RPF, which was successfully validated by the mutagenesis of PAH and derivative mixture mimic-simulating PM2.5 samples collected in eastern China. This study provides fast reliable tools for assessing risk of the complex components of environmental PAHs and their derivatives.

Mutagenic and Cancer Risk Estimation of Particulate Bound Polycyclic Aromatic Hydrocarbons from the Emission of Different Biomass Fuels.

Smoke samples from combustion of different biomass fuels were analyzed for the particulate bound Polycyclic Aromatic Hydrocarbons (PAHs) due to their carcinogenic and mutagenic nature. Out of 16 priority PAHs, 11 PAHs were detected in the emission of fuels, while the remaining 5 PAHs (chrysene, benzo[b]fluoranthene, benzo[k]fluoranthene, indeno[1,2,3-cd]pyrene, and benzo[g,h,i]perylene) were below the detection limit. The highest emission factor for the sum of all the PAHs was found for coal (353.08 mg kg-1), charcoal (27.28 mg kg-1), and the various wood types. Emission rates of total PAHs ranged from 0.37 to 5.15 mg h-1 with the highest value for bituminous coal (5.15 mg h-1) and lowest for Polyalthia longifolia (0.37 mg h-1). A cancer risk assessment was done for infants, children, and adults using the incremental lifetime cancer risk (ILCR) model via ingestion, inhalation, and dermal contact pathway. The ILCR values ranged from 10-11 to 10-6, and a higher cancer risk was observed for children and adults in comparison to infants. PAH concentrations emitted from biomass emissions shows a direct correlation with mutagenesis to humans, indicating a higher potential for the frameshift mutation as compared to base-pair mutation for dung, bituminous coal, charcoal, Dalbergia sissoo, Psidium guajava, Ziziphus mauritana, Polyalthia longifolia, and Ailanthus trithesa.

Chicken embryonic toxicity and potential in vitro estrogenic and mutagenic activity of carvacrol and thymol in low dose/concentration

Thymol and carvacrol are phenolic isomers with the potential developmental toxicity and endocrine disruptions (ED) at low concentrations. However, few reports estimated their toxicity and ED below 10−6 M (150 μg/L) (MW of thymol and carvacrol: 150 g/mol). In this study, both chemicals were determined for the developmental toxicity and potential ED at 500 μg/kg and 50 μg/kg using the chicken embryonic assay, potential estrogenic activity (EA) at 10−12 to 10−7 M (1.5 × 10−4 to 15 μg/L) by the MCF-7 cell proliferation assay, mutagenicity at 10−12 to 10−6 M (1.5 × 10−4 to 150 μg/L) by the Ames test, and an in silico method for ED. Carvacrol showed mutagenic risks at 10−7, 10−8, and 10−11 M (15, 1.5, and 0.0015 μg/L) while thymol at 10−6 and 10−8 M (150 and 1.5 μg/L). Carvacrol negatively impacted embryonic growth at 50 μg/kg, with weak EA at 10−8 M (1.5 μg/L). Carvacrol but not thymol had weak EA at 10−12 M (1.5 × 10−4 μg/L). Molecular docking to 14 types of hormone-related receptors revealed that carvacrol had higher binding affinities to two estrogen receptors and the mineralocorticoid receptor than those to thymol. Carvacrol and thymol varied in toxicities due to a different location of one phenolic hydroxyl group.

Polycyclic Aromatic Hydrocarbons in Fresh and Smoked Clupea heregus and Hake Fish Consumed in Ekiti State, Nigeria and their Health Implications

Levels of polycyclic aromatic hydrocarbons (PAHs) in fresh and smoked Clupea herengus (shawa) andHake (panla) fish commonly consumed in Ekiti State, Nigeria were investigated using gas chromatographicmethod. Effect of smoking on the PAHs level was also considered. The PAHs concentration ranged from0.0001 µg/kg Acenapthene and Indeo (1,2,3-cd) pyrene to 0.240 µg/kg (Benzo (a) pyrene) for fresh unsmokedClupea herengus (SF), 0.0001µg/kg Acenapthene and Anthracene to 0.638 µg/kg Benzo (b) fluoranthene forsmoked C. herengus (SF), 0.0001 µg/kg Acenapthene, Anthracene, Fluoranthene and Benzo(ghi) peryleneand Indeno(1,2,3-cd)pyrene to 0.171 µg/kg (Benzo (a) pyrene) for fresh Hake (panla) fish (PF) and 0.0001µg/kg Indeno(1,2,3-cd)pyrene to 0.966 µg/kg pyrene for smoked Hake (panla) fish (PS) samples. Resultsalso revealed TPAHs levels in the smoked fish were 62.3-62.5% times higher than the fresh. Values of PAHslevels in the fish samples were below EU-regulatory limits (30µg/kg) for PAHs. Hazard index and lifetimeexcess carcinogenic risk of the samples revealed no potential cancer and mutagenic risks.

ASSESSMENT OF PESTICIDES AND POLYCYCLIC AROMATIC HYDROCARBONS IN BEEF JERKY MEAT FROM NIGERIA AND THEIR DIETARY CONCENTRATION TO HUMAN

The study reports the concentrations, daily intake levels and possible potential health risks of 33 pesticides and 16 polycyclic aromatic hydrocarbons (PAHs) in beef jerky meat samples collected from sellers in Ado-Ekiti, Nigeria. The PAHs concentration (µg/kg) ranged from 0.007 (indeno(1,2,3-cd)pyrene) to 0.516 (acenapthylene), while pesticides (µg/kg) ranged from 0.010(2,4,6-trichlorophenol) to 0.272 (oxamyl). The estimated daily intakes of the pesticides were within the acceptable daily intakes (EDI˂˂˂ADI). The hazard indices were significantly less than 1 (HI ˂˂ 1) with estimated range of 1.08 × 10-7 (pyriproxyfen) to 1.81 × 10-4 (aldrin). Non carcinogenic equivalent (mg/kg/day) intakes of PAHs from beef jerky consumption ranged from 0.000027 (pyrene) to 0.00421 (anthracene), while the carcinogenic equivalent concentration ranged from 0.000024 (chrysene) to 0.265 benzo(a)pyrene. The risk associated with beef jerky meat showed no potential non-carcinogenic and carcinogenic risk while mutagenic and carcinogenic risk revealed low potential health risk as compared to the guideline value (1.0 × 10-6) for potential cancer risk.

OESTADODAARTE DE COMPOSTOS CARBONÍLICOSVOLÁTEISEMAMBIENTES INTERNOS:IMPACTOSÀ SAÚDEEMETODOLOGIAS DEAMOSTRAGEMEANÁLISES

THE STATE OF THE ART OF VOLATILE CARBONYL COMPOUNDS IN INTERNAL ENVIRONMENTS: IMPACTS TO HEALTH AND SAMPLING METHODOLOGIES AND ANALYSIS. The primary sources of emission of volatile carbonyl compounds (CCs) in indoor environments are chipboard panels, laminate floors, plywood, paints and solvents, household products, fiberglass, gas stoves, heaters and heating systems. Several studies have already confirmed an indoor/outdoor (I/O) ratio greater than 1 (one) for several CCs, indicating that these compounds are emitted mainly from internal sources. CCs (especially aldehydes and ketones) are easily absorbed into the airways, presenting a considerable mutagenic, teratogenic and carcinogenic risk to humans. Therefore, this study aimed to review the CCs found in different indoor environments, the effects and impacts of these compounds on human health and the national and international guidelines that establish their maximum exposure limits. The methodologies most used in the literature to analyze CCs in the air were reviewed directly (in real-time) or indirectly (using pre-treatment steps). A detailed review of the sampling techniques: with and without adsorption, with and without derivatization, with adsorption and derivatization simultaneously; using various methodologies employed during the last decades (cartridges, filters, tubes or liquid absorbent-impinger) was carried out. Finally, this work describes the instrumental methods and the advantages and disadvantages of determining CCs individually and simultaneously in the atmosphere.

Optimization of brain-penetrant picolinamide derived leucine-rich repeat kinase 2 (LRRK2) inhibitors.

The discovery of potent, kinome selective, brain penetrant LRRK2 inhibitors is the focus of extensive research seeking new, disease-modifying treatments for Parkinson's disease (PD). Herein, we describe the discovery and evolution of a picolinamide-derived lead series. Our initial optimization efforts aimed at improving the potency and CLK2 off-target selectivity of compound 1 by modifying the heteroaryl C-H hinge and linker regions. This resulted in compound 12 which advanced deep into our research operating plan (ROP) before heteroaryl aniline metabolite 14 was characterized as Ames mutagenic, halting its progression. Strategic modifications to our ROP were made to enable early de-risking of putative aniline metabolites or hydrolysis products for mutagenicity in Ames. This led to the discovery of 3,5-diaminopyridine 15 and 4,6-diaminopyrimidine 16 as low risk for mutagenicity (defined by a 3-strain Ames negative result). Analysis of key matched molecular pairs 17 and 18 led to the prioritization of the 3,5-diaminopyridine sub-series for further optimization due to enhanced rodent brain penetration. These efforts culminated in the discovery of ethyl trifluoromethyl pyrazole 23 with excellent LRRK2 potency and expanded selectivity versus off-target CLK2.

Concentration levels, Carcinogenic and Mutagenic risks of PM2.5-bound Polycyclic Aromatic Hydrocarbons in an urban-industrial area in South Africa

Background: Concerns over the health effects of exposure to particulate matter of aerodynamic diameter of less than 2.5 μm (PM2.5) led the South African Government to establish the national standard for PM2.5 in the year 2012. However, there is currently no exposure limit for polycyclic aromatic hydrocarbons (PAHs) and PM2.5-bound PAHs. The understanding of the concentration levels and potential health risks of exposure to PM2.5-bound PAHs is important in ensuring a suitable risk assessment and risk management plan. This study, therefore, determined the concentration levels, carcinogenic and mutagenic health risks of PM2.5-bound PAHs. Methods: A hundred and forty-four PM2.5 samples were collected over four months during the winter and summer seasons of 2016 in an industrial area. The concentrations of 16 PAHs were analysed by gas chromatography-mass spectrometry, and their carcinogenic and mutagenic risks determined using the Human Health Risk Assessment model. Results: The mean winter (38.20±8.4 μg/m3) and summer (22.3±4.1 μg/m3) concentrations of PM2.5 levels were lower than the stipulated 40 μg/m3 daily limit. The main PAHs in PM2.5 were the lower molecular weight compounds accounting for 59.0% of the total concentration. The daily inhalation and ingestion exposure to PAHs for all age groups were higher than the daily exposure through the dermal contact. Children and adults are more likely to inhale and ingest PAHs in PM2.5 than infants. The excess cancer risks and excess mutagenic risk values were below the priority risk level (10-4). There is a potential risk of 1 to 8 per million persons developing cancer from exposure to Benzo[a]anthracene, Benzo[a]pyrene, Indeno[1,2,3-cd]pyrene, and Dibenz[a,h]anthracene over a lifetime of 70 years.Conclusions: The measured PAHs presented a seasonal variation, with higher concentrations observed in winter. These findings can equip relevant stakeholders and policymakers with the knowledge to institute strategies and plans for further emissions control.

Phytochemical composition and in vitro safety evaluation of Ziziphora clinopodioides Lam. ethanolic extract: Cytotoxicity, genotoxicity and mutagenicity assessment

Ethnopharmacological relevanceThe application of the herb Ziziphora clinopodioides Lam. in folk medicine and as a food additive has been recommended due to its many claimed bioactivities. Regardless of the plant benefits, its safety considerations are largely unknown. Aim of the studyThe aim of the present research was to determine the chemical compositions and cytotoxicity, genotoxicity, and mutagenicity potentials of the ethanolic extract of Ziziphora clinopdioides Lam. (EEZC). Materials and methodsGC-MS and LC-MS analysis were used for chemical composition determination. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and trypan blue exclusion dye assays were used for cytotoxicity and the Comet assay was employed for genotoxicity assessment on human blood lymphocytes. Also, the Ames Salmonella/microsome test was carried out for the evaluation of mutagenicity. ResultsPulegone was the main component of the n-hexane fraction. Different phenolic acids and flavonoids were detected by LC-MS. The cytotoxicity study indicated a conspicuous decline in human lymphocyte viability ranging from 52% to 100% as showed by the MTT assay and 67% up to 100% by the trypan blue assay, at 1 and 10 mg/mL, respectively. The Comet assay results revealed a dose dependent genotoxicity, in so much as 90% and 98% of the cells were screened as damaged at concentrations of 5 and 10 mg/mL, respectively. An incidence rate of 8% and 13% of grade 4 damage was observed at 5 and 10 mg/mL, respectively. Additionally, the DNA damage index (DI) was elevated dose-dependently by a rising concentration of the extract, wherein the DI at 10 mg/mL concentration was 2.22, which was 22 times greater than that of negative control, and even more than positive control. The Ames test exhibited no signs of mutagenicity for neither Salmonella typhimurium TA98 nor TA100 strains, accompanied or unaccompanied by S9 metabolic activation. ConclusionResults indicated a dose-dependent cytotoxicity and genotoxicity potential of the EEZC on human lymphocytes, suggesting that this plant should be used with caution by consumers, even in the food and pharmaceutical industries. Since the plant usage in daily life continues to increase due to its ever growing phytotherapical and phytonutritional properties, it may pose a health risk by its high concentration's uptake. Although no mutagenicity of this extract was observed in this study, further research is recommended to clarify the mutagenic risks of this herb.

Purification of arsenic-contaminated water using iron molybdate filters and monitoring of their genotoxic, mutagenic, and cytotoxic effects through bioassays.

Environmental contamination has been a cause of concern worldwide, being aggravated by anthropogenic activities carried out without the correct disposal of toxic products in the various habitats on our planet. In Brazil, mining companies are responsible for the contamination of large river basins with toxic elements from mining activities. Among these elements, arsenic draws attention because it is highly carcinogenic and found in waters in concentrations above those recommended by regulatory agencies. Here, Fe2(MoO4)3 nanoparticles are synthesized and used as a filter medium in water purification systems contaminated with arsenic. The adsorption kinetics of arsenic by Fe2(MoO4)3 nanoparticles is fast, showing pseudo-second-order rate constants of 0.0044, 0.0080, and 0.0106gmg-1min-1 for As3+, As5+, and MMA, respectively. The adsorption isotherms are better adjusted with the Langmuir and Redlich-Peterson models, indicating that the arsenic adsorption occurs in monolayers on the Fe2(MoO4)3 surface. The Fe2(MoO4)3 adsorption capacities determined for the As3+, As5+, and MMA species are 16.1, 23.1, and 23.5mgg-1, respectively. The Fe2(MoO4)3 filter is efficient in purifying arsenic-contaminated water, reducing its initial concentration from 1000μgL-1 to levels close to zero. Biological tests indicate that Fe2(MoO4)3 nanoparticles and filtered water have no cytotoxic, genotoxic, and mutagenic risks to human life. Those results suggest that the Fe2(MoO4)3 filter can be used as an efficient and safe technology for the purification of water contaminated by arsenic.

Enhancing solar disinfection (SODIS) with the photo-Fenton or the Fe2+/peroxymonosulfate-activation process in large-scale plastic bottles leads to toxicologically safe drinking water

Solar disinfection (SODIS) in 2-L bottles is a well-established drinking water treatment technique, suitable for rural, peri‑urban, or isolated communities in tropical or sub-tropical climates. In this work, we assess the enlargement of the treatment volume by using cheap, large scale plastic vessels. The bactericidal performance of SODIS and two solar-Fe2+ based enhancements, namely photo-Fenton (light/H2O2/Fe2+) and peroxymonosulfate activation (light/PMS/Fe2+) were assessed in 19-L polycarbonate (PC) and 25-L polyethylene terephthalate (PET) bottles, in ultrapure and real water matrices (tap water, lake Geneva water). Although SODIS always reached total (5-logU) inactivation, under solar light, enhancement by or both Fe2+/H2O2 or Fe2+/PMS was always beneficial and led to an increase in bacterial elimination kinetics, as high as 2-fold in PC and PET bottles with tap water for light/H2O2/Fe2+, and 8-fold in PET bottles with Lake Geneva water. The toxicological safety of the enhancements and their effects on the plastic container materials was assessed using the E-screen assay and the Ames test, after 1-day or 1-week exposure to SODIS, photo-Fenton and persulfate activation. Although the production of estrogenic compounds was observed, we report that no treatment method, duration of exposure or material resulted in estrogenicity risk for humans, and similarly, no mutagenicity risk was measured. In summary, we suggest that SODIS enhancement by either HO•- or SO4•−-based advanced oxidation process is a suitable enhancement of bacterial inactivation in large scale plastic bottles, without any associated toxicity risks.

In vivo mutagenicity evaluation of the soil fumigant 1,3-dichloropropene

1,3-Dichloropropene (1,3-D; CAS No. 542-75-6) is a soil fumigant used for the control of nematodes in agriculture. There is an extensive database on the genotoxicity of 1,3-D and many of the published studies are confounded by the presence of mutagenic stabilisers in the test substance. Mixed results were obtained in the in vitro assays, often due to the purity of the 1,3-D sample tested. In order to get further clarity, the mutagenic potential of 1,3-D was investigated in vivo in the transgenic Big Blue rodent models. Inhalation exposure of 150 ppm 1,3-D (×2.5 tumourigenic dose) to transgenic male B6C3F1 mice did not induce lacI mutations in either the lung (tumour target tissue) or liver. Similarly, dietary administration of 1,3-D up to 50 mg/kg/day to transgenic male Fischer 344 rats did not increase the cII mutant frequency in either the liver (tumour target) or kidney. These results, along with other available in vivo data, including the absence of DNA adducts and clastogenic/aneugenic potential, support the conclusion that 1,3-D is efficiently detoxified in vivo and, as such, does not pose a mutagenic hazard or risk.

Meat intake, meat cooking methods, and meat-derived mutagen exposure and risk of sessile serrated lesions

Red and processed meat, recognized carcinogens, are risk factors for colorectal neoplasia, including polyps, the precursor for colorectal cancer. The mechanism is unclear. One possible explanation is the mutagenic activity of these foods, perhaps due to generation during cooking [e.g., heterocyclic amine (HCA) intake]. Few studies have evaluated meat intake and sessile serrated lesion (SSL) risk, a recently recognized precursor, and no study has evaluated meat cooking methods and meat-derived mutagens with SSL risk. We evaluated intakes of meat, meat cooking methods, and inferred meat mutagens with SSL risk and in comparison to risk of other polyps. Meat, well-done meat, and inferred meat mutagen intakes were evaluated. Polytomous logistic regression models were used to estimate ORs and 95% CIs among cases (556 hyperplastic polyp, 1753 adenoma, and 208 SSL) and controls (3804) in the large colonoscopy-based, case-control study, the Tennessee Colorectal Polyp Study. The highest quartile intakes of red meat (OR: 2.38; 95% CI: 1.44, 3.93), processed meat (OR: 2.03; 95% CI: 1.30, 3.17), well-done red meat (OR: 2.19; 95% CI: 1.34, 3.60), and the HCA 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQX; OR: 2.48; 95% CI: 1.49, 4.16) were associated with increased risk of SSLs in comparison to the lowest quartile intake. High intakes of red and processed meats are strongly and especially associated with SSL risk and part of the association may be due to HCA intake. Future studies should evaluate other mechanism(s) and the potential for primary prevention.

Current Molecular Markers of Melanoma and Treatment Targets.

Melanoma is a deadly skin cancer that becomes especially difficult to treat after it metastasizes. Timely identification of melanoma is critical for effective therapy, but histopathologic diagnosis can frequently pose a significant challenge to this goal. Therefore, auxiliary diagnostic tools are imperative to facilitating prompt recognition of malignant lesions. Melanoma develops as result of a number of genetic mutations, with UV radiation often acting as a mutagenic risk factor. Novel methods of genetic testing have improved detection of these molecular alterations, which subsequently revealed important information for diagnosis and prognosis. Rapid detection of genetic alterations is also significant for choosing appropriate treatment and developing targeted therapies for melanoma. This review will delve into the understanding of various mutations and the implications they may pose for clinical decision making.

Detection of genotoxic effect of potassium permanganate by using in vitro micronucleus assay

Objective: Hydrogen peroxide is a bleaching agent accepted as safe for environment and used for producing cotton fabrics. This process requires alkaline medium, stabilizer and high temperature. For this purpose, it is used extensively in the textile industry. Potassium permanganate is a widely used agent in our country as it is easier to obtain compared to other oxidizing agents. In this study, we investigated whether occupational exposure to potassium permanganate causes genotoxic effect or not. Method: This cross-sectional study was carried out in a denim factory located in the Organized Industrial Zone in Sivas. The total number of employees was 600 in the factory including 50 workers in the office and 550 workers in the production department. The study group was consisted of 32 healthy males, non-smokers, without chronic diseases and infections. They had been working at least 2 years in denim bleaching unit. The control group was consisted of 30 healthy male volunteers, at similar age, non-smokers, working in administrative or desk jobs in the same factory, with little or no risk of chemical exposure. Workers who had an infection in the last month and who were on medication were excluded from the study. In Vitro Micronucleus Test was used to determine the genotoxic effect of potassium permanganate. The venous blood samples taken from the workers and controls was cultured in laboratory conditions according to Fenech’s method with minor modifications. Evaluation of slides was carried out according to Fenech’s microscopic survey criteria at ×1000 magnification. The frequencies of the total number of micronuclei in the lymphocytes (MNL) and bi-nucleated cells with the micronuclei (BNMN) were determined. In addition, to determine the frequencies of nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs), 1000 nucleated cells with well-preserved cytoplasm were also evaluated. Student’s T-test was used for statistical evaluation. Results: When groups were compared, the micronucleus frequency was detected as about twice high in study group. Statistically significant difference was detected between the study and control group (p 0.05). Conclusions: Indicators of genotoxic effect were higher in the group with potassium permanganate exposure than the control group. High micronucleus and nuclear bud frequencies in the study group may be indicative of genotoxicity. It may be thought that clastogenic and mutagenic risk increases for employees. Keywords: Potassium permanganate, micronucleus, nucleoplasmic bridge, nuclear bud, genotoxicity