Onco-pharmacogenesis or pharmaco-oncogenesis of skin cancer is a concept , which could also be considered as an \"end product\" of drug-mediated Nitrosogenesis or of the permissive regime for carcinogens to be (un)controlled released in drugs. Their controlled distribution remains until 2025 as a forced and non-alternative and there is no indication of any possibility to introduce a full elimination regime against the already mentioned carcinogenic availability. There are three main worrying facts that determine the need for these elimination regimes: 1) the clinicopathological correlations concerning the intake of a heterogeneous class of drugs and the subsequent development of relatively homogeneous tumours/ such as melanoma, 2) the recently proven mutagenic/ carcinogenic action of certain nitrosamines, but this time directly on human DNA, and 3) the fact that some of the nitrosamines are potent photocarcinogens that exert their genotoxic effects only after irradiation with UVA/ also recently proven/. In addition to the rhetoric mentioned above, there is also an overlap in mutational patterns between the genes previously generally accepted to affect melanomas - p53 / RAS oncogenes , with those identified as target genes, but being affected \"mutationally\", by certain nitrosamines. The processes of photocarcinogenesis, nitrosogenesis and oncopharmacogenesis of skin cancer are inextricably linked and should not be considered and analysed unilaterally or in a semi-invasive manner. Cataloguing the type of nitrosamines and their precise concentration on drug leaflets and prescription/official websites with permanent access to clinicians and end-users remains the only safe and effective weapon in the fight against (un)controlled contamination. The pharmaceutical industry and regulators remain the creators, the \'parents\' of onco-pharmacogenesis, nitrosogenesis, and therefore the processes involved in the generation and progression of skin cancer. The impossibility of establishing elimination regimes for certain mutagens and/or carcinogens already proven to be present in medicines remains a mystery. In practice, end consumers find themselves in a state of enforced tolerance of certain genotoxic substances that are not even declared as available. Clinicians in the face of dermatologists/ dermatological surgeons remain the analysers and identifiers of these globalization processes. Once again, we present a patient who took the antiarrhythmic (nitroso-) drug propafenone and developed a relatively short-term nodular melanoma with a subsequent fatal outcome. We comment on the role of drug-mediated nitrosogenesis and its relationship to photocarcinogenesis and onco-pharmacogenesis.

Despite the fact that the pathogenesis of cutaneous melanoma is shrouded in mystery, factors that have been neglected or unnoticed until now have come to the attention in recent years, and in all likelihood, they could also be pivotal. These factors, known as nitrosamines or NDSRIs, are characterized by high carcinogenic and mutagenic potency, and some of them have demonstrated these properties to human DNA as well. Unfortunately, these ingredients also turn up as contaminants in about 300 of the most widely distributed drugs worldwide. According to the most recent literature, some of these ingredients are also identified as potent photocarcinogens, as well as human carcinogens. The intake of these carcinogens in the context of polycontamination of polymedication, has been associated for years with the occurrence of melanomas. The need for cataloguing of nitrosamines , as well as their accurate labelling on drug packaging, would help to classify them even more accurately as carcinogens affecting human DNA. We present once again a patient , who developed nodular melanoma within the context of the intake of 3 potentially nitrosamine/ NDSRIs contaminated antihypertensive drugs (valsartan/ Hydrochlorothiazide/ bisoprolol). Pathogenetic aspects concerning drug-induced nitrosogenesis, photocarcinogenesis and oncopharmacogenesis of skin cancer are discussed. Nitrosogenesis\' of Cancer as concept in the medical literature has been known for decades, but in relation to other forms of human cancer. Exogenously mediated drug-mediated nitrosogenesis is a logically conditioned and newly defined concept whose significance with respect to the clinical manifestation of skin cancer is only beginning to grow.

This study aimed to investigate the occurrence of eight nitrosamines (NAs) in particulate (PM2.5) and gaseous phases and assess the human health risk associated with these compounds in an urban area of Chuncheon, Gangwon State, South Korea, across four sampling seasons. The findings revealed that the total concentrations of eight NAs measured during the sampling period exceeded the public health recommendation of 0.3 ng/m3 provided by the Norwegian Institute of Public Health, indicating a potential human health risk from NA exposures. In particular, the average total NA concentration observed in the gaseous samples during the winter of 2021 was 18.1 ± 6.46 ng/m3. The primary emission sources could potentially impact the concentrations of NAs in the atmosphere due to their significant positive correlation with primary emission species such as NO2, CO, and SO2. Moreover, the levels of particulate NAs during the summer were negatively correlated with O3, suggesting that their formation might be influenced by ozonation in the aqueous aerosol phase. In addition, the total NA concentrations measured in the gaseous phase were four to six times higher than those measured in the PM2.5 phase throughout the sampling period. Thus, domestic sources have the potential to impact the pollution levels of the research area more significantly than long-range atmospheric transport. In particular, the highest concentrations of NAs in the gas phase were observed during the winter, while the lowest concentrations were recorded in the summer, possibly influenced by photolysis. Nevertheless, the study suggested that tertiary amines might contribute to the presence of gaseous NAs in sunlight. Consequently, further studies focusing on the occurrence of tertiary amines in the gas phase should be considered. The cumulative lifetime cancer risks estimated from inhalation exposure exceeded the acceptable risk level of 10⁻6 for all age groups across all four seasons. Therefore, it is crucial to implement effective control measures to mitigate potential health risks associated with exposure to NAs.

The idea of drug-induced/exogenic Nitrosogenesis is driven by the possibility of prolonged exposure of the human body to the influence of nitrosamines within the drug intake - substances or contaminants that have been proven to be carcinogenic or mutagenic one.Until recently, there was a complete lack of data in the scientific literature on the relationship between cancer, polymedication and polycontamination with nitrosamines. In the last decade, melanoma has been described repeatedly in the medical literature as a possible side-effect within the intake of possibly with nitrosamines contaminated medications such as: Valsartan, Hydrochlorothiazide, Amlodipine, Nebivolol, Bisoprolol and Perindopril. However, the contribution of the currently presented new data (5 new patients) is also due to the establishment of the possible pathogenetic role (with respect to melanoma) of several completely new drugs, previously unknown to the scientific community (potentially/actually contaminated with carcinogens/nitrosamines), such as: Ranitidine, Rosuvastatin, Lercanidipine, Rilmenidine, Trandolapril, Moxonidine and Verapamil.The leading and connecting link in shared new and old drug combinations of heterogeneous drug classes (polymedication) and melanoma development and progression remains again one and the same: the possible availability of nitroso component in the frame of exogenous nitrosogenesis according to the official FDA lists of 2023.The number of drugs shared as contaminated with nitrosamines after whose intake melanomas occur is increasing. Nitrosogenesis remains a new beginning, a new understanding and new interpretation of the carcinogenesis concerning melanoma, but probably also of cancer in general. Its further elucidation looks more than promising and is yet to come. More than worrying at the moment remains the fact that the scientific community has to clarify if: 1) peak concentrations of nitrosamines or NDSRIs within the framework of monomedication or 2) normal concentrations within the polymedication (catalogued in the list of FDA/ 2023 as potentially contaminated with hypothetical carcinogens), could hide relatively short-term risk of the development of real tumors: cutaneous melanomas and/or their precursor lesions. The validation of the concept of Nitrosogenesis and its relationship to Сarcinogenesis, is achieved in practice on the basis of the following facts: that it is the occurrence of the same monomorphic clinical pattern (melanoma/dysplastic nevi), developing after the intake of drugs with different mechanism of action, contaminated with nitrosamines/NDSRIs. The unifying link between the intake of certain drugs and the development of certain tumours remains the presence of nitrosamines. Ingredients that are present in drug preparations, identified as availability and as carcinogenic potency, but not yet reflected in packaging or prescriptions. The question remains: why?

The unexpected finding of N-nitrosamine (NA) impurities in many pharmaceutical products raised significant challenges for industry and regulators. In addition to well-studied small molecular weight NAs, many of which are potent rodent carcinogens, novel NAs associated with active pharmaceutical ingredients have been found, many of which have limited or no safety data. A tiered approach to establishing Acceptable Intake (AI) limits for NA impurities has been established using chemical-specific data, read-across, or a class-specific TTC limit. There are ∼140 NAs with some rodent carcinogenicity data, but much of it is older and does not meet current guidelines for what constitutes a \'robust\' bioassay. Nevertheless, these data are an important source of information to ensure the best science is used for assessing NA impurities and assuring consumer safety while minimizing impact that can lead to drug shortages. We present several strategies to maximize the use of imperfect data including using a lower confidence limit on a rodent TD50, and leveraging data from multiple NAs. Information on the chemical structure known to impact potency can also support development of an AI or potentially conclude that a particular NA does not fall in the cohort of concern for potent carcinogenicity.

Passive exposure to the aerosols of electronic cigarettes (e-cigarettes) has been little studied. We assessed this exposure in late pregnancy in a woman and her 3-year-old child, exposed through e-cigarette use by another household member.
This prospective longitudinal case study involved a family unit consisting of an e-cigarette user, a pregnant woman who delivered an infant during the study, and the couple\'s older 3-year-old son. At 31, 36, and 40 weeks of the pregnancy, we measured biomarkers (nicotine metabolites, tobacco-specific nitrosamines, propanediols, glycerol, and metals) in the urine and hair of all three participants and in the saliva of the adults, in cord blood at delivery, and in the breast milk at the postpartum period.
Samples from the e-cigarette user showed quantifiable concentrations of all analytes assessed (maximum urinary cotinine concentration, 4.9 ng/mL). Among samples taken from the mother, nicotine and its metabolites were found mainly in urine and also in saliva and hair, but not in cord blood. During the postpartum period, we found cotinine concentrations of 2.2 ng/mL in the mother\'s urine and 0.22 ng/mL in breast milk; 1,2-propanediol was generally detected in urine and saliva, but not in cord blood or breast milk. The maximum urinary cotinine concentration in the 3-year-old child was 2.6 ng/mL and propanediols also were detected in his urine. Nitrosamines were not detected in samples taken from the mother or the 3-year-old. Metals found in the refill liquid were detected at low levels in both the mother and the 3-year-old.
We detected low but not negligible concentrations of e-cigarette-related analytes (including cord blood and breast milk) in an exposed pregnant non-user and in a 3-year-old child also living in the home. Passive exposure to e-cigarette aerosols cannot be disregarded and should be assessed in larger observational studies.

Introduction: The known connections between the terms \'sartans\' and \'melanoma\' has grown recently in the clinical field, suggesting that the relationship between these concepts is very likely to be significant, rather than hypothetical or unfeasible. This is because: 1) the presence of angiotensin receptors in melanoma tissue, melanocytes and skin is a known fact; 2) the influence of sartans on the processes of melanogenesis has already been presented in recent published scientific papers; 3) key in vitro studies have shown that angiotensin receptor blockers (sartans) could potentiate carcinogenesis in the direction of melanoma and metastases; and 4) clinical examples of the occurrence of melanoma after starting therapy with sartans have become numerous and difficult to ignore.Areas covered: We report the first case of occult melanoma in an 87-year-old Bulgarian patient, this manifested in the form of a solitary metastasis on the left arm, which occurred after long-term therapy with telmisartan.Expert opinion: The fact that nitrosamines have a proven carcinogenic effect and are the cause of heterogeneous neoplasms shows that they have the potential to be possible melanoma triggers. The multifactorial pathogenesis of melanoma could certainly be clarified after the \'crystallization\' of this currently serious issue.

The drinking water sources of many cities in southern China are frequently contaminated by upstream urban drainage during storm events, which brings high concentrations of N-nitrosamine (NA) precursors and poses a threat to the safety of drinking water. We conducted two sampling campaigns during the heavy rain season in 2015 in one representative city in southern China. We detected that the concentration of N-nitrosodimethylamine formation potential (NDMA FP) in urban drainage during two storm events was 80-115 ng/L and the total formation potential concentration of nine nitrosamines (TNA9 FP) was 145-165 ng/L. To address the deteriorated water quality, 30 mg/L of powdered activated carbon (PAC) was fed into the water intake. PAC adsorption alone could remove 52% of NDMA FP and 52% of TNA FP, while the subsequent conventional process only removed 8% of TNA FP. We isolated six chemicals (N,N-benzyldimethylamine, 5-[(dimethylamino)methyl]-2-furanmethanol, N,N-dimethyl-3-aminophenol, N,N-dimethylethylamine, Ziram, and N,N-dimethylaniline) and confirmed them to be NA precursors. Among these NA precursors, Ziram was identified for the first time as a NA precursor that is formed via chloramination; its molar yield for NDMA was 6.73 ± 0.40%.

A basic tenet of empirical research on cigarette smoking behavior is the systematic assessment of patterns of use. However, the large majority of extant research relies on smokers\' retrospective reports of their average number of cigarettes per day (CPD), a measure that may be variable in terms of reliability and validity. Using data from 3 previously published studies of non-treatment-seeking daily smokers (combined N = 89), this analysis examined the reliability of self-reported CPD, the consistency of returned cigarette butts each day over 4 consecutive 24-hr periods, the validity of self-reported CPD compared with returned cigarette butts, and the relationship of CPD and returned cigarette butts to toxicant exposure. Results showed that self-reported CPD was reliable across telephone and in-person screening interviews (r = .87, p < .01). Although average self-reported CPD and returned cigarette butt counts did not differ significantly, t(87) = -1.5 to 0.3, all ns, butt counts revealed a wider range of variability in daily smoking behavior. In addition, self-reported cigarette use exhibited substantial digit bias (Whipple\'s index = 413.8), meaning that participants tended to round their estimates to values ending in 0 or 5. Cigarette butt counts, but not self-reported CPD, were significantly associated with exposure to smoke toxicants. However, this former relationship was revealed to be linear, but not curvilinear, in nature. These findings have implications for both research and treatment efforts, as researchers often rely on accurate assessment of CPD to predict a variety of smoking-related outcomes. (PsycINFO Database Record

BACKGROUND: Environmental tobacco smoking (ETS) significantly contributes to morbidity and mortality and is a known risk factor for lung cancer development in lifelong nonsmokers. The metabolite 4-(methylnitrosamino)- 1-(3-pyridyl)-1-butanol (NNAL) and its glucuronides (NNAL-Glucs) have now emerged as leading biomarkers for the study of carcinogen exposure in non-smokers exposed to ETS.
METHODS: We carried out our study on NNAL in the urine of non-smokers exposed to ETS and the association between ETS and lung cancer. Subjects were enrolled from 2008-2010. NNAL was analyzed for 74 non-smoking lung cancer and 85 healthy controls. The main objective of this study was to provide an estimate of the risk of lung cancer from exposure to ETS in the Korean population.
RESULTS: The mean NNAL concentration in urine was significantly lower in non-smoking patient groups (n=74) than in control groups (n=85) (4.7±15.0 pg/mg, 6.5 ± 17.9 pg/mg, respectively, Mann-Whitney U test, p<0.001).
CONCLUSIONS: The urine NNAL of non-smoking patients with lung cancer was not elevated with regard to the non-smoking control group. This may be due to life-style changes after diagnosis. A prospective study will be needed to evaluate the association of NNAL and non-smoking lung cancer.