- MeSH
- alternativy testů na zvířatech * MeSH
- technologie * MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- úvodníky MeSH
Triclosan and Triclocarban, preservatives widely used in cosmetics and other consumer products, underwent evaluation using a battery of new-approach methodologies in vitro (NAMs). Specifically, the Microplate Ames Test (MPFTM Test, Xenometrix, Allschwil, Switzerland) was employed to assess mutagenicity, the Comet assay in vitro on the HaCat cell line and the Mammalian Chromosome Aberration Test were utilized to evaluate genotoxicity, and the XenoScreen® YES/YAS assay was applied to investigate endocrine disruption. The chemicals did not exhibit any positive responses for mutagenicity. However, the mammalian chromosome aberration test identified both chemicals as being positive for genotoxicity at 10 μg/mL. In the Comet assay, the percentage of DNA in the tail significantly increased in a concentration-dependent manner (at 5 and 10 μg/mL for Triclosan, at 2.5, 5, and 10 μg/mL for Triclocarban). The positive response depended on the increasing concentration and the duration of exposure. Triclosan, but not Triclocarban in any of the endocrine assays performed, indicated a potential for endocrine activity in the anti-estrogenic and anti-androgenic assays. The positive in vitro results detected were obtained for concentrations relevant to final products. The alarming findings obtained with the use of new-approach methodologies (NAMs) justify the current precautionary regulatory approach, limiting the use of these preservatives.
- Publikační typ
- časopisecké články MeSH
V léčbě pacientů s metastatickým kastračně senzitivním karcinomem prostaty (mCSPC) došlo v průběhu posledních let k významnému pokroku. Zatímco u pacientů s méně rozsáhlým či méně agresivním onemocněním je doporučena kombinace androgenní deprivace (ADT) a hormonálních léků zaměřených na inhibici signalizace androgenního receptoru (ARTA), u pacientů v dobrém celkovém stavu s velkým rozsahem onemocnění, a především se synchronními metastázami, je novým standardem léčby intenzifikovaná iniciální terapie tripletem ADT + ARTA + docetaxel.
There has been significant progress in recent years in the treatment of patients with metastatic castration-sensitive prostate cancer (mCSPC). While for patients with less extensive or less aggressive disease, a combination of androgen deprivation (ADT) and hormonal agents aimed at inhibiting androgen receptor signaling (ARTA) is recommended, for patients in good overall condition with high-volume disease and especially synchronous metastases, the new standard of treatment is intensified initial therapy using a triplet of ADT+ARTA+docetaxel.
- MeSH
- antagonisté androgenních receptorů farmakologie klasifikace terapeutické užití MeSH
- antitumorózní látky farmakologie terapeutické užití MeSH
- hormonální substituční terapie klasifikace MeSH
- klinické zkoušky, fáze III jako téma MeSH
- kombinovaná farmakoterapie metody MeSH
- lidé MeSH
- nádory prostaty * farmakoterapie MeSH
- randomizované kontrolované studie jako téma MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- přehledy MeSH
Animal testing has been prohibited for the safety assessment of cosmetic ingredients or finished products. Thus, alternative non-animal methods, followed by confirmatory clinical studies on human volunteers, should be used as the sole legally acceptable approach within the EU. The safety assessment of cosmetic products requires the involvement of multiple scientific disciplines, including analytical chemistry and biomedicine, as well as in chemico, in vitro and in silico toxicology. Recent data suggest that fragrance components may exert multiple adverse biological effects, e.g. cytotoxicity, skin sensitisation, (photo)genotoxicity, mutagenicity, reprotoxicity and endocrine disruption. Therefore, a pilot study was conducted with selected samples of fragrance-based products, such as deodorant, eau de toilette and eau de parfum, with the aim of integrating results from a number of alternative non-animal methods suitable for the detection of the following toxicological endpoints: cytotoxicity (with 3T3 Balb/c fibroblasts); skin sensitisation potential (in chemico method, DPRA); skin sensitisation potential (LuSens in vitro method, based on human keratinocytes); genotoxicity potential (in vitro Comet assay with 3T3 Balb/c cells); and endocrine disruption (in vitro YES/YAS assay). The presence of twenty-four specific known allergens in the products was determined by using GC-MS/MS. The strategies for estimation of the NOAEL of a mixture of allergens, which were proposed by the Scientific Committee on Consumer Products in their 'Opinion on Tea tree oil' document and by the Norwegian Food Safety Authority in their 'Risk Profile of Tea tree oil' report, were used as models for the NOAEL estimation of the mixtures of allergens that were identified in the individual samples tested in this study.
- MeSH
- alergeny toxicita analýza MeSH
- kosmetické přípravky * toxicita MeSH
- lidé MeSH
- parfém * analýza MeSH
- pilotní projekty MeSH
- plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
- tandemová hmotnostní spektrometrie MeSH
- tea tree oil * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Indoor air is typically a mixture of many chemicals at low concentrations without any adverse health effects alone, but in mixtures they may cause toxicity and risks to human health. The aim of this study was by using new approach methods to assess the potential toxicity of indoor air condensates. In specific, different in vitro test methods including cyto-and immunotoxicity, skin sensitization and endocrine disruption were applied. In addition to biological effects, the indoor air samples were subjected to targeted analysis of 25 volatile organic compounds (VOCs) and Genapol X-80 (a nonionic emulsifier) suspected to be present in the samples, and to a non-targeted "total chemical scan" to find out whether the chemical composition of the samples is associated with the biological effects. The results confirm that assessing health risks of indoor air by analysing individual chemicals is not an adequate approach: We were not able to detect the VOCs and Genapol X-80 in the indoor air samples, yet, several types of toxicity, namely, cytotoxicity, immunotoxicity, skin sensitization and endocrine disruption were detected. In the non-targeted total chemical scan of the indoor air samples, a larger number of compounds were found in the cytotoxic samples than in the non-cytotoxic samples supporting the biological findings. If only one biological method would be selected for the screening of indoor air quality, THP-1 macrophage/WST-1 assay would best fit for the purpose as it is sensitive and serves as a good representative for different sub-toxic end points, including immunotoxicity, (skin) sensitization and endocrine disruption.
- Publikační typ
- časopisecké články MeSH
- MeSH
- časové faktory MeSH
- endokrinní disruptory aplikace a dávkování metabolismus toxicita MeSH
- lidé MeSH
- metabolické nemoci chemicky indukované epidemiologie metabolismus MeSH
- rozmnožování účinky léků fyziologie MeSH
- vystavení vlivu životního prostředí škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- úvodní články MeSH
- úvodníky MeSH
Medical devices must be tested before marketing in accordance with ISO EN 10993-10 in order to avoid skin sensitization. This standard predominantly refers to the in vivo test but does not exclude the use of in vitro methods that have been sufficiently technically and scientifically validated for medical device testing. It is foreseen that, due to the complexity of the sensitization endpoint, a combination of several methods will be needed to address all key events occurring in the sensitization process. The objective of this pilot study was to evaluate the sensitization potential of selected medical devices using a combination of in chemico (DPRA, OECD TG 442C) and in vitro (LuSens, OECD TG 442D) methods in comparison with the in vivo (LLNA DA, OECD TG 442A) method and to suggest a possible testing strategy for the safety assessment of medical device extracts. Overall, one of the 42 tested samples exhibited positive results in all employed test methods, while 33 samples were predicted as non-sensitizing in all three performed methods. This study demonstrated good agreement between in vitro and in vivo results regarding non-sensitizing samples; however, some discrepancies in positive classification were recorded. A testing strategy is suggested in which negative results are accepted and any positive results in the in chemico or in vitro tests are followed up with a third in vitro test and evaluated in accordance with the “2 out of 3 approach”. This strategy may reduce and replace animal use for testing the sensitization potential of medical devices.
- MeSH
- alergická kontaktní dermatitida * MeSH
- alternativy testů na zvířatech * MeSH
- biotest MeSH
- kůže MeSH
- pilotní projekty MeSH
- techniky in vitro MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
Growing worldwide efforts to replace (reduce) animal testing and to improve alternative in vitro tests which may be more efficient in terms of both time, cost and scientific validity include also genotoxicity/mutagenicity endpoints. The aim of the review article was to summarize currently available in vitro testing approaches in this field, their regulatory acceptance and recommended combinations for classification of chemicals. A study using the combination of Comet Assay performed on two cell lines and the Chromosomal Aberration test on human peripheral lymphocytes was performed with the aim to predict the genotoxic potential of selected paraben esters, serving as a model chemical group. Parabens are widely used in consumer products as preservatives and have been reported to exhibit inconclusive results in numerous genotoxicity studies. The Comet Assay identified Ethylparaben and Benzylparaben as potentially genotoxic. The Chromosomal Aberration test revealed weak genotoxic potential in case of Ethylparaben and positive genotoxicity in case of Butylparaben, Propylparaben and Isopropylparaben. The main reasons for variability seem to be limited water solubility of parabens, determining their bioavailability at the cellular level, and absence of metabolic activation in the Comet Assay. The results confirmed that the Comet Assay should serve as a screening test and should not be used as a stand-alone method for classification of genotoxicity. The weight of evidence approach in risk assessment should be supported with data generated with the use of human relevant in vitro methods based on cells / tissues of human origin.
- MeSH
- alternativy testů na zvířatech * MeSH
- buněčné linie keratinocytů HaCaT MeSH
- chromozomální aberace chemicky indukované MeSH
- hodnocení rizik MeSH
- kometový test MeSH
- lidé MeSH
- lymfocyty účinky léků patologie MeSH
- mikrojaderné testy MeSH
- mikrojádra chromozomálně defektní chemicky indukované MeSH
- mutageneze účinky léků MeSH
- parabeny toxicita MeSH
- poškození DNA * MeSH
- testy genotoxicity * MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- srovnávací studie MeSH
