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1.
Environ Res ; 255: 119118, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38763278

RESUMO

Polycyclic aromatic hydrocarbons (PAH) are persistent environmental pollutants, which occasionally appear as contaminants in consumer products. Upon dermal contact, transfer of PAH into the stratum corneum (s.c.) and migration through the skin may occur, resulting in this class of highly toxic compounds to become bioavailable. In this study, dermal penetration through human and porcine skin of 24 PAH, comprising broad molar mass (M: 152-302 g/mol) and octanol-water partition coefficient (logP: 3.9-7.3) ranges, was evaluated via Franz diffusion cell in vitro assays. More lipophilic and potentially more toxic PAH had decreased permeation rates through the rather lipophilic s.c. into the more hydrophilic viable (epi-)dermis. Furthermore, human skin was less permeable than pigskin, a commonly used surrogate in skin penetration studies. In particular, the s.c. of human skin retains a greater share of PAH, an effect that is more pronounced for smaller PAH. Additionally, we compared the skin permeation kinetics of different PAH in pigskin. While small PAH (M < 230 g/mol, logP < 6) permeate the skin quickly and are detected in the receptor fluid after 2 h, large PAH (M > 252 g/mol, logP ≥ 6) do not fully permeate the skin up to 48 h. This indicates that highly lipophilic PAH do not become bioavailable as readily as their smaller congeners when transferred to the skin surface. Our data suggest that pigskin could be used as a surrogate for worst case scenario estimates of dermal PAH permeation through human skin.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Absorção Cutânea , Pele , Hidrocarbonetos Policíclicos Aromáticos/farmacocinética , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Hidrocarbonetos Policíclicos Aromáticos/química , Humanos , Animais , Suínos , Pele/metabolismo , Permeabilidade , Técnicas In Vitro , Feminino , Adulto
2.
Ecotoxicol Environ Saf ; 262: 115113, 2023 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-37315362

RESUMO

In this study, we determined partition (Ksc/m) and diffusion (Dsc) coefficients of five different polycyclic aromatic hydrocarbons (PAH) migrating from squalane into and through the stratum corneum (s.c.) layer of the skin. Carcinogenic PAH have previously been detected in numerous polymer-based consumer products, especially those dyed with carbon black. Upon dermal contact with these products, PAH may penetrate into and through the viable layers of the skin by passing the s.c. and thus may become bioavailable. Squalane, a frequent ingredient in cosmetics, has also been used as a polymer surrogate matrix in previous studies. Ksc/m and Dsc are relevant parameters for risk assessment because they allow estimating the potential of a substance to become bioavailable upon dermal exposure. We developed an analytical method involving incubation of pigskin with naphthalene, anthracene, pyrene, benzo[a]pyrene and dibenzo[a,h]pyrene in Franz diffusion cell assays under quasi-infinite dose conditions. PAH were subsequently quantified within individual s.c. layers by gas chromatography coupled to tandem mass spectrometry. The resulting PAH depth profiles in the s.c. were fitted to a solution of Fick's second law of diffusion, yielding Ksc/m and Dsc. The decadic logarithm logKsc/m ranged from -0.43 to +0.69 and showed a trend to higher values for PAH with higher molecular masses. Dsc, on the other hand, was similar for the four higher molecular mass PAH but about 4.6-fold lower than for naphthalene. Moreover, our data suggests that the s.c./viable epidermis boundary layer represents the most relevant barrier for the skin penetration of higher molecular mass PAH. Finally, we empirically derived a mathematical description of the concentration depth profiles that better fits our data. We correlated the resulting parameters to substance specific constants such as the logarithmic octanol-water partition coefficient logP, Ksc/m and the removal rate at the s.c./viable epidermis boundary layer.

3.
mBio ; 12(5): e0122321, 2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34579573

RESUMO

Polycyclic aromatic hydrocarbons (PAH) such as benzo[a]pyrene (B[a]P) are among the most abundant environmental pollutants, resulting in continuous exposure of human skin and its microbiota. However, effects of the latter on B[a]P toxicity, absorption, metabolism, and distribution in humans remain unclear. Here, we demonstrate that the skin microbiota does metabolize B[a]P on and in human skin in situ, using a recently developed commensal skin model. In this model, microbial metabolism leads to high concentrations of known microbial B[a]P metabolites on the surface as well as in the epidermal layers. In contrast to what was observed for uncolonized skin, B[a]P and its metabolites were subject to altered rates of skin penetration and diffusion, resulting in up to 58% reduction of metabolites recovered from basal culture medium. The results indicate the reason for this altered behavior to be a microbially induced strengthening of the epidermal barrier. Concomitantly, colonized models showed decreased formation and penetration of the ultimate carcinogen B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE), leading, in consequence, to fewer BPDE-DNA adducts being formed. Befittingly, transcript and expression levels of key proteins for repairing environmentally induced DNA damage such as xeroderma pigmentosum complementation group C (XPC) were also found to be reduced in the commensal models, as was expression of B[a]P-associated cytochrome P450-dependent monooxygenases (CYPs). The results show that the microbiome can have significant effects on the toxicology of external chemical impacts. The respective effects rely on a complex interplay between microbial and host metabolism and microbe-host interactions, all of which cannot be adequately assessed using single-system studies. IMPORTANCE Exposure to xenobiotics has repeatedly been associated with adverse health effects. While the majority of reported cases relate to direct substance effects, there is increasing evidence that microbiome-dependent metabolism of xenobiotic substances likewise has direct adverse effects on the host. This can be due to microbial biotransformation of compounds, interaction between the microbiota and the host's endogenous detoxification enzymes, or altered xenobiotic bioavailability. However, there are hardly any studies addressing the complex interplay of such interactions in situ and less so in human test systems. Using a recently developed microbially competent three-dimensional (3D) skin model, we show here for the first time how commensal influence on skin physiology and gene transcription paradoxically modulates PAH toxicity.


Assuntos
Benzo(a)pireno/metabolismo , Microbiota/efeitos dos fármacos , Microbiota/fisiologia , Pele/efeitos dos fármacos , Pele/microbiologia , Simbiose/efeitos dos fármacos , Benzo(a)pireno/farmacologia , Técnicas de Cultura de Células , Dano ao DNA/genética , Reparo do DNA/genética , Humanos , Técnicas In Vitro , Microbiota/genética , Pele/metabolismo , Fenômenos Fisiológicos da Pele/efeitos dos fármacos , Simbiose/fisiologia
4.
Artigo em Inglês | MEDLINE | ID: mdl-34246168

RESUMO

New nicotine delivery products are gaining market share. For evaluation of their characteristics, toxicokinetic investigations are in current research focus. For reliable determination of blood plasma levels of nicotine and its main metabolites cotinine and trans-3'-hydroxycotinine, a quantitation method based on LC-ESI-MS/MS was developed and validated. Addition of isotope labeled internal standards prior to rapid sample preparation using protein precipitation with methanol was chosen for sample preparation. Different stationary phases were tested and phenyl-hexyl separation was found to be superior to HILIC, C18, and C8 stationary phases. Ion suppression effects caused by hydrophilic early eluting matrix were eliminated by the adjustment of an adequate retention utilizing a phenyl-hexyl separation stationary phase. Exchange of acetonitrile as organic mobile phase by methanol and elevation of pH value of aqueous mobile phase containing 5 mM NH4Ac to 4.50 improved the chromatographic resolution. The limits of quantitation for nicotine, cotinine, and hydroxycotinine were 0.15, 0.30, and 0.40 ng/mL, respectively. Linearity was proven by matrix matched calibration for the whole working range from 0.50 ng/mL to 35.0 ng/mL for nicotine and from 6.00 to 420 ng/mL for cotinine and hydroxycotinine (Mandel's fitting test with R2 > 0.995). Quality control samples at four different levels (0.50, 1.50, 17.5, 28.0 ng/mL for nicotine and 6.00, 18.0, 210, 336 ng/mL for cotinine and hydroxycotinine) in plasma were analyzed six times on three days. Mean accuracies ranged from 87.7% to 105.8% for nicotine, from 90.3% to 102.9% for cotinine, and from 99.9% to 109.9% for hydroxycotinine. Intra- and inter-day precisions (RSD %) were below 15% for all analytes (<20% for LLOQ). As proof of concept, the method was successfully applied to a real plasma sample from a cigarette smoking volunteer.


Assuntos
Cromatografia Líquida/métodos , Cotinina/análogos & derivados , Cotinina/sangue , Espectrometria de Massas em Tandem/métodos , Adulto , Humanos , Limite de Detecção , Modelos Lineares , Masculino , Reprodutibilidade dos Testes
5.
Sci Rep ; 11(1): 12078, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34103661

RESUMO

The emergence of e-cigarettes on the consumer market led to a tremendous rise in e-cigarette consumption among adolescents in the United States. The success of JUUL and other pod systems was linked to its high nicotine delivery capacity. In compliance with the European Tobacco Product directive, liquid nicotine contents in the European JUUL variants are limited to 20 mg/mL or below. A short time after launching the initial version in Europe, JUUL pods have been modified in terms of the wick material used. This modification has been demonstrated previously to lead to an elevated aerosol generation, consequently, to a larger amount of nicotine per puff generated. The present study was designed to assess whether the mentioned differences between the "initial" and "modified" JUUL versions may cause a significant difference during consumption, and how nicotine delivery compares with tobacco cigarettes. In this single-center three-arm study, nicotine pharmacokinetics and influence on urge to smoke/vape were compared for tobacco cigarettes, the "initial" version of the European JUUL, and the "modified" version of the European JUUL. Participants, 15 active smokers and 17 active e-cigarette users, were instructed to consume their study product according to a pre-directed puffing protocol. Venous blood was sampled for nicotine analysis to cover the acute phase and the first 30 min after starting. Nicotine delivery and the reduction of urge to smoke/vape upon usage of both European JUUL variants were lower in comparison to tobacco cigarettes. This suggests a lower addictive potential. Modification of the pod design did not result in significant differences at the first ten puffs, as confirmed by a vaping machine experiment. Apparently, the limitations by the initially used wick material only come into effect after longer usage time.


Assuntos
Fissura/efeitos dos fármacos , Sistemas Eletrônicos de Liberação de Nicotina , Nicotina , Vaping/sangue , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nicotina/administração & dosagem , Nicotina/farmacocinética
6.
Chem Res Toxicol ; 34(1): 132-143, 2021 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-33400513

RESUMO

Plastic costume masks regularly exhibit unpleasant odors that may be associated with the emissions of volatile organic compounds (VOCs). Upon inhalation, VOCs might adversely affect the wearer's health if the exposure exceeds regulatory threshold values. The VOCs emitted from a selection of costume masks (n = 12) were characterized semiquantitatively with a screening method based on GC/MS measurements in dynamic headspace sampling mode. Furthermore, odors associated with the masks were evaluated by a sensory panel. Two masks emitted particularly high concentrations of ethylbenzene, xylenes, and cyclohexanone and exhibited the most intense and unpleasant odors, which were described as rubber-like, pungent, and leather-like. To simulate and assess the inhalation exposures for wearers of these masks, an innovative experimental setup based on a doll's head was developed, with sampling of emitted volatiles on adsorption material and subsequent analysis by thermal desorption-GC/MS. The measured inhalable concentrations of cyclohexanone exceeded the derived no-effect level (DNEL) for systemic effects on the general population over several hours of wearing, and also after repeated use. Importantly, the cyclohexanone DNEL was reevaluated in relation to a recent study on inhalation toxicity in rodents and was found to be significantly lower (1.4 mg·m-3) compared to the industry-derived values (10-20 mg·m-3), thus aggravating the health risks associated with inhalation exposure from some of the costume masks tested. Finally, a comparison of the inhalable concentrations derived from the simulated exposure assessments with those derived from measurements in miniaturized emission test chambers indicate that microchambers represent a useful tool for high-throughput analysis. The influences of temperature and inhalation/exhalation flow rates on VOC exposures were also studied.


Assuntos
Exposição por Inalação/análise , Polímeros/química , Compostos Orgânicos Voláteis/análise , Animais , Monitoramento Ambiental , Cromatografia Gasosa-Espectrometria de Massas , Compostos Orgânicos Voláteis/toxicidade
7.
Materials (Basel) ; 14(2)2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33430314

RESUMO

Formaldehyde is considered as carcinogenic and is emitted from particleboards and plywood used in toy manufacturing. Currently, the flask method is frequently used in Europe for market surveillance purposes to assess formaldehyde release from toys, but its concordance to levels measured in emission test chambers is poor. Surveillance laboratories are unable to afford laborious and expensive emission chamber testing to comply with a new amendment of the European Toy Directive; they need an alternative method that can provide reliable results. Therefore, the application of miniaturised emission test chambers was tested. Comparisons between a 1 m3 emission test chamber and 44 mL microchambers with two particleboards over 28 days and between a 24 L desiccator chamber and the microchambers with three puzzle samples over 10 days resulted in a correlation coefficient r2 of 0.834 for formaldehyde at steady state. The correlation between the results obtained in microchambers vs. flask showed a high variability over 10 samples (r2: 0.145), thereby demonstrating the error-proneness of the flask method in comparison to methods carried out under ambient parameters. An exposure assessment was also performed for three toy puzzles: indoor formaldehyde concentrations caused by puzzles were not negligible (up to 8 µg/m3), especially when more conservative exposure scenarios were considered.

9.
Arch Toxicol ; 94(6): 1985-1994, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32189038

RESUMO

The popularity and the high nicotine content of the American pod e-cigarette JUUL have raised many concerns. To comply with European law, the nicotine concentration in the liquids of the European version, which has been recently released on the market, is limited to below 20 mg/mL. This limit can possibly be circumvented by technological adjustments that increase vaporization and consequently, elevate nicotine delivery. In this study, we compare vapor generation and nicotine delivery of the initial European version, a modified European version, and the original American high-nicotine variant using a machine vaping set-up. Additionally, benzoic acid and carbonyl compounds are quantified in the aerosol. Further, concentrations of nicotine, benzoic acid, propylene glycol, and glycerol, along with the density and pH value of JUUL e-liquids have been assessed. Whereas the initial European version did not compensate for the low nicotine content in the liquid, we provide evidence for an increased vaporization by the modified European version. As a consequence, nicotine delivery per puff approximates the American original. Notably, this is not associated with an increased generation of carbonyl compounds. Our data suggest a similar addictiveness of the enhanced European version and the original American product.


Assuntos
Vapor do Cigarro Eletrônico/análise , Sistemas Eletrônicos de Liberação de Nicotina , Nicotina/análise , Agonistas Nicotínicos/análise , Vaping , Aerossóis , Qualidade de Produtos para o Consumidor , Vapor do Cigarro Eletrônico/efeitos adversos , Europa (Continente) , Humanos , Nicotina/efeitos adversos , Agonistas Nicotínicos/efeitos adversos , Medição de Risco , Vaping/efeitos adversos
10.
Indoor Air ; 30(1): 40-48, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31544292

RESUMO

The ISO 16000 standard series provide guidelines for emission measurements of volatile organic compounds (VOCs) from building materials. However, polymer-based consumer products such as toys may also release harmful substances into indoor air. In such cases, the existing standard procedures are unsuitable for official control laboratories due to high costs for large emission testing chambers. This paper aims at developing and comparing alternative and more competitive methods for the emission testing of consumer products. The influence of the emission chamber size was investigated as smaller chambers are more suited to the common size of consumer products and may help to reduce the costs of testing. Comparison of the performance of a 203 L emission test chamber with two smaller chambers with the capacity of 24 L and 44 mL, respectively, was carried out by using a polyurethane reference material spiked with 14 VOCs during the course of 28 days. The area-specific emission rates obtained in the small chambers were always similar to those of the 203 L reference chamber after a few hours. This implies that smaller chambers can provide at least useful numbers on the extent of polymer-based consumer product emissions into indoor air, thereby supporting meaningful exposure assessments.


Assuntos
Poluição do Ar em Ambientes Fechados/análise , Materiais de Construção/análise , Monitoramento Ambiental , Polímeros/análise , Compostos Orgânicos Voláteis/análise
11.
Front Public Health ; 7: 287, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31649912

RESUMO

The health risks of tobacco smoking have been documented in numerous studies and smoking rates have declined in developed countries over the last 50 years. Today, we know that cigarette smoking is the major cause of preventable deaths due to tobacco smoke induced diseases. As a consequence of an increased awareness of smoking-related health risks, heated tobacco products (HTPs) are marketed as reduced toxicant alternatives to conventional tobacco products. Manufacturers claim that levels of toxicants and hazardous compounds are significantly reduced, implying that inhalation of the modified aerosol is less harmful compared to conventional cigarettes. In this manuscript, previous assessments of HTPs are briefly summarized, including a short discussion on challenges with the adaption of standard analytical methods used for tobacco smoke. The reliability of analytical data is important for risk assessment approaches that are based on reduced toxicant exposure. In order to assess a putative reduction of health risks, an integrated study design is required that should include clinical studies and epidemiology data. One manufacturer applied for a classification as a Modified Risk Tobacco Product (MRTP) in the United States, based on extensive toxicological studies that have also been published. However, data are not yet sufficient for a reliable assessment or recognition of putatively reduced health risks. Challenges regarding a classification in Europe are also discussed briefly in this review.

12.
Front Public Health ; 7: 202, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31475125

RESUMO

The development of consumerism led to an increase in toy production. Such consumer products may contain non-intentionally added toxic substances that can emit from the product and may be inhaled by the consumer. Little data is available on the inhalation exposure of humans to volatile organic compounds (VOCs) from consumer products, so a reliable exposure assessment is needed. Only the emission chamber technique developed for building material emissions can provide solid estimations as it allows the products to be studied under real room conditions. This paper proposes a strategy to interpret emission experiment results from consumer products and assess the corresponding potential risk. It focuses on 14 common VOCs. The identification of the polymer type of 41 plastic articles was first performed by pyrolysis coupled online to gas chromatography with mass spectrometric detection (pyr-GC/MS). Their VOC profile was also determined by Dynamic Headspace-GC/MS (DHS-GC/MS). Softer polymers caused higher and broader emission profiles. Four specific toy samples were selected to be studied in a 203 l emission chamber and their emissions were compared to a reference material. A rapid decrease in the emissions was observed for each product and VOC. Based on these emission curves over time, the corresponding indoor air concentration could be calculated for the target VOCs for short-term or long-term exposures. The indoor air levels obtained were at least 35 times lower than the levels according to conventional indoor air guidelines. Guideline values were only exceeded using very conservative exposure scenarios.

13.
J Vis Exp ; (147)2019 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-31180344

RESUMO

Tattoo inks are complex mixtures of ingredients. Each of them possesses different chemical properties which have to be addressed upon chemical analysis. In this method for two-step pyrolysis online coupled to gas chromatography mass spectrometry (py-GC-MS) volatile compounds are analyzed during a first desorption run. In the second run, the same dried sample is pyrolyzed for analysis of non-volatile compounds such as pigments and polymers. These can be identified by their specific decomposition patterns. Additionally, this method can be used to differentiate original from counterfeit inks. Easy screening methods for data evaluation using the average mass spectra and self-made pyrolysis libraries are applied to speed up substance identification. Using specialized evaluation software for pyrolysis GS-MS data, a fast and reliable comparison of the full chromatogram can be achieved. Since GC-MS is used as separation technique, the method is limited to volatile substances upon desorption and after pyrolysis of the sample. The method can be applied for quick substance screening in market control surveys since it requires no sample preparation steps.


Assuntos
Cosméticos/química , Tinta , Tatuagem , Corantes/análise , Cromatografia Gasosa-Espectrometria de Massas , Polímeros/análise , Pirólise , Compostos Orgânicos Voláteis/análise
14.
Crit Rev Toxicol ; 49(9): 742-789, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31939687

RESUMO

For a few years, mineral oils and their potential adverse health effects have been a constant issue of concern in many regulatory areas such as food, cosmetics, other consumer products, and industrial chemicals. Analytically, two fractions can be distinguished: mineral oil saturated hydrocarbons (MOSH) and mineral oil aromatic hydrocarbons (MOAH). This paper aims at assessing the bioaccumulative potential and associated histopathological effects of MOSH as well as the carcinogenic potential of MOAH for consumer-relevant mineral oils. It also covers the absorption, distribution, metabolism, and excretion of MOSH and MOAH upon oral and dermal exposures. The use and occurrence of consumer-relevant, highly refined mineral oils in food, cosmetics and medicinal products are summarized, and estimates for the exposure of consumers are provided. Also addressed are the challenges in characterizing the substance identity of mineral oil products under REACH. Evidence from more recent autopsy and biopsy studies, along with information on decreasing food contamination levels, indicates a low risk for adverse hepatic lesions that may arise from the retention of MOSH in the liver. With respect to MOAH, at present there is no indication of any carcinogenic effects in animals dermally or orally exposed to highly refined mineral oils and waxes. Such products are used not only in cosmetics but also in medicinal products and as additives in food contact materials. The safety of these mineral oil-containing products is thus indirectly documented by their prevalent and long-term use, with a simultaneous lack of clinical and epidemiological evidence for adverse health effects.


Assuntos
Cosméticos , Contaminação de Alimentos , Óleo Mineral , Animais , Exposição Ambiental/estatística & dados numéricos , Humanos , Hidrocarbonetos/análise , Hidrocarbonetos Aromáticos/análise
16.
Arch Toxicol ; 92(6): 2145-2149, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29730817

RESUMO

Consumers of combustible cigarettes are exposed to many different toxicologically relevant substances associated with negative health effects. Newly developed "heat not burn" (HNB) devices are able to contain lower levels of Harmful and Potentially Harmful Constituents (HPHCs) in their emissions compared to tobacco cigarettes. However, to develop toxicological risk assessment strategies, further independent and standardized investigations addressing HPHC reduction need to be done. Therefore, we generated emissions of a commercially available HNB product following the Health Canada Intense smoking regimen and analyzed total particulate matter (TPM), nicotine, water, aldehydes, and other volatile organic compounds (VOCs) that are major contributors to health risk. We show that nicotine yield is comparable to typical combustible cigarettes, and observe substantially reduced levels of aldehydes (approximately 80-95%) and VOCs (approximately 97-99%). Emissions of TPM and nicotine were found to be inconsistent during the smoking procedure. Our study confirms that levels of major carcinogens are markedly reduced in the emissions of the analyzed HNB product in relation to the conventional tobacco cigarettes and that monitoring these emissions using standardized machine smoking procedures generates reliable and reproducible data which provide a useful basis to assess exposure and human health risks.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Nicotina/efeitos adversos , Material Particulado/efeitos adversos , Fumaça/efeitos adversos , Produtos do Tabaco , Compostos Orgânicos Voláteis/efeitos adversos , Poluentes Atmosféricos/análise , Canadá , Temperatura Alta , Nicotina/análise , Material Particulado/análise , Medição de Risco , Fumaça/análise , Compostos Orgânicos Voláteis/análise
17.
Arch Toxicol ; 91(6): 2331-2341, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28378121

RESUMO

The ubiquitous occurrence of polycyclic aromatic hydrocarbons (PAHs) leads to constant human exposure at low levels. Toxicologically relevant are especially the high-molecular weight substances due to their (pro-)carcinogenic potential. Following ingestion or uptake, the eukaryotic phase I metabolism often activates these substances to become potent DNA binders, and unsurprisingly metabolism and DNA-adduct formation of model substances such as benzo[a]pyrene (B[a]P) are well studied. However, apart from being subjected to eukaryotic transformations PAHs are also carbon and energy sources for the myriads of commensal microbes inhabiting man's every surface. Yet, we know little about the microbiome's PAH-metabolism capacity and its potentially adverse impact on the human host. This study now shows that readily isolable skin commensals transform B[a]P into a range of highly cyto- and genotoxic metabolites that are excreted in toxicologically relevant concentrations during growth. The respective bacterial supernatants contain a mixture of established eukaryotic as well as hitherto unknown prokaryotic metabolites, the combination of which leads to an increased toxicity. Altogether we show that PAH metabolism of the microbiome has to be considered a potential hazard.


Assuntos
Bacillus licheniformis/metabolismo , Dano ao DNA , Queratinócitos/efeitos dos fármacos , Micrococcus luteus/metabolismo , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Pele/efeitos dos fármacos , Bacillus licheniformis/genética , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ensaio Cometa , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Queratinócitos/metabolismo , Queratinócitos/microbiologia , Desintoxicação Metabólica Fase I , Microbiota , Micrococcus luteus/genética , Pele/metabolismo , Pele/microbiologia
18.
Toxicol Lett ; 271: 50-57, 2017 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-28238800

RESUMO

Activation of the cold-receptor TRPM8 by menthol or other tobacco additives can suppress natural defense reactions such as coughing that usually would become effective as involuntary resistance against the inhalation of fumes. In Europe menthol is only regulated as flavor, but can be used as additive as long as no characteristic mint-like aroma will become noticeable in the end-product tobacco. The question needs to be addressed of whether such comparatively minor contents would be sufficient to trigger a measurable activation of TRPM8. In this study, we have analyzed both the contents of menthol and other natural TRPM8 agonists in tobacco products and developed a bioassay to determine the minimum concentrations of selected agonists to activate the TRPM8 receptor in cultured cells. The data confirm menthol as strongest natural agonist investigated. Based on these experiments and previously published data, we have estimated both the minimum menthol concentrations in cigarette smoke and in tobacco that are expected to trigger measurable physiological effects. According to our assessments, TRPM8 activation is likely to occur when cigarettes contain more than 50 micrograms of menthol. Importantly, menthol contents in cigarettes far below the typical levels that require declaration as "mentholated" would be sufficient to activate sensory receptors.


Assuntos
Mentol/toxicidade , Fumaça/efeitos adversos , Fumar/efeitos adversos , Canais de Cátion TRPM/agonistas , Produtos do Tabaco/toxicidade , Bioensaio , Sinalização do Cálcio/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células HEK293 , Humanos , Canais de Cátion TRPM/genética , Canais de Cátion TRPM/metabolismo , Transfecção
19.
Int J Hyg Environ Health ; 219(8): 780-791, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27622657

RESUMO

According to European legislation, tobacco additives may not increase the toxicity or the addictive potency of the product, but there is an ongoing debate on how to reliably characterize and measure such properties. Further, too little is known on pyrolysis patterns of tobacco additives to assume that no additional toxicological risks need to be suspected. An on-line pyrolysis technique was used and coupled to gas chromatography-mass spectrometry (GC/MS) to identify the pattern of chemical species formed upon thermal decomposition of 19 different tobacco additives like raw cane sugar, licorice or cocoa. To simulate the combustion of a cigarette it was necessary to perform pyrolysis at inert conditions as well as under oxygen supply. All individual additives were pyrolyzed under inert or oxidative conditions at 350, 700 and 1000°C, respectively, and the formation of different toxicants was monitored. We observed the generation of vinyl acrylate, fumaronitrile, methacrylic anhydride, isobutyric anhydride and 3-buten-2-ol exclusively during pyrolysis of tobacco additives. According to the literature, these toxicants so far remained undetectable in tobacco or tobacco smoke. Further, the formation of 20 selected polycyclic aromatic hydrocarbons (PAHs) with molecular weights of up to 278Da was monitored during pyrolysis of cocoa in a semi-quantitative approach. It was shown that the adding of cocoa to tobacco had no influence on the relative amounts of the PAHs formed.


Assuntos
Aromatizantes , Nicotiana , Compostos Orgânicos/análise , Acer , Chocolate , Café , Qualidade de Produtos para o Consumidor , Sucos de Frutas e Vegetais , Cromatografia Gasosa-Espectrometria de Massas , Glycyrrhiza , Mel , Temperatura Alta , Extratos Vegetais , Gomas Vegetais , Raízes de Plantas , Prunus domestica , Saccharum , Amido
20.
Arch Toxicol ; 90(7): 1639-50, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27209489

RESUMO

The implementation of regulation for tattoo ink ingredients across Europe has generated the need for analytical methods suitable to identify prohibited compounds. Common challenges of this subject are the poor solubility and the lack of volatility for most pigments and polymers applied in tattoo inks. Here, we present pyrolysis coupled to online gas chromatography and electron impact ionization mass spectrometry (py-GC/MS) as quick and reliable tool for pigment identification using both purified pigments and tattoo ink formulations. Some 36 organic pigments frequently used in tattoo inks were subjected to py-GC/MS with the aim to establish a pyrogram library. To cross-validate pigment identification, 28 commercially available tattoo inks as well as 18 self-made pigment mixtures were analyzed. Pyrograms of inks and mixtures were evaluated by two different means to work out the most reliable and fastest strategy for an otherwise rather time-consuming data review. Using this approach, the declaration of tattoo pigments currently used on the market could be verified. The pyrolysis library presented here is also assumed suitable to predict decomposition patterns of pigments when affected by other degradation scenarios, such as sunlight exposure or laser irradiation. Thus, the consumers' risk associated with the exposure to toxicologically relevant substances that originate from pigment decomposition in the dermal layers of the skin can be assessed. Differentiation between more or less harmful pigments for this field of application now will become feasible.


Assuntos
Corantes/química , Corantes/toxicidade , Substâncias Perigosas/química , Substâncias Perigosas/toxicidade , Tinta , Tatuagem/efeitos adversos , Corantes/efeitos da radiação , Cromatografia Gasosa-Espectrometria de Massas , Substâncias Perigosas/efeitos da radiação , Humanos , Valor Preditivo dos Testes , Solubilidade , Luz Solar , Volatilização
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