Relative carcinogenicity of tacrolimus vs mycophenolate after solid organ transplantation and its implications for liver transplant care

BACKGROUND De novo malignancy is a leading cause of late morbidity and mortality in liver transplant recipients.Cumulative immunosuppression has been shown to contribute to post-transplant malignancy(PTM)risk.There is emerging evidence on the differential carcinogenic risk profile of individual immunosuppressive drugs,independent of the net effect of immunosuppression.Calcineurin inhibitors such as tacrolimus may promote tumourigenesis,whereas mycophenolic acid(MPA),the active metabolite of mycophenolate mofetil,may limit tumour progression.Liver transplantation(LT)is relatively unique among solid organ transplantation in that immunosuppression monotherapy with either tacrolimus or MPA is often achievable,which makes careful consideration of the risk-benefit profile of these immunosuppression agents particularly relevant for this cohort.However,there is limited clinical data on this subject in both LT and other solid organ transplant recipients.AIM To investigate the relative carcinogenicity of tacrolimus and MPA in solid organ transplantation.METHODS A literature search was conducted using MEDLINE and Embase databases using the key terms“solid organ transplantation”,“tacrolimus”,“mycophenolic acid”,and“carcinogenicity”,in order to identify relevant articles published in English between 1st January 2002 to 11th August 2022.Related terms,synonyms and explosion of MeSH terms,Boolean operators and truncations were also utilised in the search.Reference lists of retrieved articles were also reviewed to identify any additional articles.Excluding duplicates,abstracts from 1230 records were screened by a single reviewer,whereby 31 records were reviewed in detail.Full-text articles were assessed for eligibility based on pre-specified inclusion and exclusion criteria.RESULTS A total of 6 studies were included in this review.All studies were large population registries or cohort studies,which varied in transplant era,type of organ transplanted and immunosuppression protocol used.Overall,there was no clear difference demonstrated between tacrolimus and MPA in de novo PTM risk following solid organ transplantation.Furthermore,no study provided a direct comparison of carcinogenic risk between tacrolimus and MPA monotherapy in solid organ transplantation recipients.CONCLUSION The contrasting carcinogenic risk profiles of tacrolimus and MPA demonstrated in previous experimental studies,and its application in solid organ transplantation,is yet to be confirmed in clinical studies.Thus,the optimal choice of immunosuppression drug to use as maintenance monotherapy in LT recipients is not supported by a strong evidence base and remains unclear.

MUTAGENICITY AND CARCINOGENICITY OF FISH SAUCE FROM A COUNTY WITH THE HIGH RISK FOR GASTRIC CANCER IN CHINA

The mutagenicity and carcinogenicity of fish sauce (FS) sample from Changle County, a high gastric cancer mortality (113.20/105) area, were investigated with the biologic short-term tests and laboratory animal experiment. The results showed that the extract of FS was markedly direct mutagenic toward S. typhimurium TA100, induced high sister chromatid exchanges (SCE) and micronucleus (MN) in V79 cells after nitrosation with sodium nitrite. But the non-nitrosated FS did not. The nitrosated fish sauce (NFS) also induced SOS in E. coli PQ37 and alkylation of calfthymus DNA. The potency of NFS to induce unscheduled DNA synthesis (UDS) in human normal gastric mucosal cells was increased about fivefold compared with FS. When the NFS extract was given to newborn rats by gavage, dys-plasia and adenocaroinoma were induced in the glandular stomach in the 4th and 16th experimental week, respectively. N-nitrosamides were also found in NFS, which may account for the mutagenicity and carcinogenicity of NFS. It is indicated that FS, a traditional daily eaten seasoning, may contribute to the causes of the high gastric cancer mortality for the local residents.

Toxicity and Carcinogenicity of Ozone in Combination with 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone and Dibutyl Phthalate in B6C3F1 Mice for 16 and 32 Weeks

Objective To evaluate the toxic and carcinogenic potential of ozone alone or in combination with 4-（N-methyl-N-nitrosamino）-1-（3-pyridyl）-1-butanone （NNK） and/or dibutyl phthalate （DBP）. Methods Male and female B6C3F1 mice were exposed, through inhalation, intravenous administration and diet, to 0.5 ppm of ozone, 1.0 mg/kg of NNK and 5000 ppm of DBP, individually and in combination for 16 and 32 weeks. Results No treatment-related death was seen, but significant differences in body and organ weights between control and treated mice were observed during the study. No incidence of lung tumor incidence was recorded in mice exposed to either ozone alone or combined treatment. Oviductal carcinomas were observed in female mice exposed to ozone or DBP alone for 16 weeks and ozone in combination with NNK and DBP for 32 weeks. Conclusion Although ozone alone and in conjunction with NNK and/or DBP does not induce lung cancer under our experimental conditions, they induce oviductal carcinomas in B6C3F1 mice.

Studies on the Mutagenicity and Teratogenicity of Kuianchun and Its Potential Carcinogenicity Prediction

Kuianchun is a newly synthesized antibacterial and growth-promoting drug. This paper selected a battery of three short-term tests, including Ames test, micronucleus test and sperm abnormality test, to detect the mutagenicity of Kuianchun. The carcinogenicity prediction and battery selection method (CPBS method) was used to determine the probability of carcinogenicity of Kuianchun based upon the results of short-term tests mentioned above. In addition, traditional teratogenic test was selected to study teratogenicity of Kuianchun. In Ames test, Kuianchun showed mutagenic for Salmonella typhimurium strains TA98 and TA100 in the absence and presence of microsomal metabolic activation system (S9-mix). However, the mutagenicity was reduced by the addition of S9-mix. In micronucleus test, Kuianchun was administered intra-peritoneally to male mouse 30 hours and 6 hours before they were killed respectively. The result indicated that there was no significant difference on the number of micronucleated polychromatic erythrocytes (PCEs) in the mouse bone marrow induced by Kuianchun compared with the negative contrast (50% DMSO) (P>0.05). In sperm abnormality test, Kuianchun was administered through a gastric incubation to male mouse as a suspension in 2% Tween-80. The dosage levels were 450, 750, 1000 and 1500mg/kg per day for 5 days. The result indicated that the percentage of abnormal sperms induced by Kuianchun was not significant compared with the negative contrast (P > 0.05). In traditional teratogenic test, Kuianchun was given orally to pregnant mouse at 1730, 1/20 and 1/15 LD50 during 6 - 15days of pregnancy period (the LD50 = 9000mg/kg). No toxicity was found either on mother and embryo in mouse, and teratogenic effects were also not observed at all tested dosages.The probability of carcinogenicity of Kuianchun is 23.8%(6 = 0.238). The result demonstrated that Kuianchun is a non-carcinogen.

Hexavalent Chrome: Threshold Concept for Carcinogenicity

Certain hexavalent chromium (Cr^(6+)) compounds when administered via inhalation at high doses have the potential to induce lung tumors in humans and experimental animals. Trivalent chromium (Cr^(3+)) is an essential human and animal nutrient at levels of 50 to 200 μg/day. Recent data have shown that the human body is able to reduce Cr^(6+) to Cr^(3+). This reduction occurs in bodily fluids such as gastric juice, epithelial lining fluid of.the respiratory tract, blood, and other fluids. Secondary reduction occurs at the cellular level by the cytosol, mitochondria, and microsomes. Thus, at low levels of exposure hexavalent chromium ions are reduced befor the 6+ ions can interact with DNA unless the dose is sufficient to overwhelm the body's reduction capacity. This paper summarizes the available data concerning the reducing ability of the body and formulates the steps in the mechanism of cancer induction. These steps include: (1) only certain Cr^(6+) compounds have the capacity to interact with cellular components; (2) Cr^(6+) is reduced by body fluids and excess Cr^(6+) enters the cell (Cr^(3+) is poorly absorbed across membranes); (3) cellular organelles and the cytoplasm reduce Cr^(6+) to Cr^(3+); (4) excess Cr^(6+) can enter the nucleus; (5) Cr^(6+) reduction through 5+ and 4+ to 3+ has a potential to interact with the DNA molecule; and (6) if unrepaired, this DNA damage can lead to cancer induction. On the basis of current evidence Cr^(6+) has a threshold for carcinogenic potential in humans that is greater than the current TLV. 1990 Academic Press. Inc.

Pairwise comparisons in the analysis of carcinogenicity data

Analysis of carcinogenicity data generally involves a trend test across all dose groups and a pairwise comparison of the high dose group with the control. The most commonly used test for a positive trend is the Cochran-Armitage test. This test is asymptotically normal. For the pairwise comparison of the high dose group with the control group, we propose two modifications: the first modification is to apply the test on the data from high dose and control groups after dropping the data from the low and the medium dose groups;the second modification is to adjust the test conditional on data from all dose groups. We compare the power performance of these two modifications for the pairwise comparisons.

CARCINOGENICITY OF FUSARIN C ISOLATED FROM FUSARIUM MONILIFORME

Fusarium monilljorme, a fungus of established carcinogenic potential, is one of the most common fungal contaminants of maize, millet and other grains in Linxian County, China. Fusarin C, a major product of F. monilljorme grown on corn in the laboratory, is mutagenic in Salmonella tester strains and in V79 cells. Fusarin C showed several characteristics of malignant transformation including the implantation of the rat esophageal epithelial cell line (RE ?525) in nude mice. The present work demonstrated that fusarin C can induce esophageal and forestomach carcinomas in DBA mice and Wistar rats, and thus the experimental results substantiated further the carcinogenicity of fusarin C.

The Anatomic Pathology Evaluation of Liver with Diethylinitrosamine Treated via Intraperitoneal Injection Singly and Peros for 90 Days Carcinogenicity Study in F344 Rats

Objective：To establish the integrity experiment method of short（ medium）- term carcinogenicity test pursuant to GLP, make into relative SOP and improve the safeguard in the center. Methods：Diethylinitrosamine（DEN） is known as carcinogenic agent, whose target organ is liver. Using the two-stage carcinogenesis test method, DEN was treated to F344 rats via intraperitoneal injection singly（200 mg/kg） , and peros administrated for 90 days（10 ppm）. The liver in any group rat will be examined by light microscopy. Results：In pathologic examination, no liver cell tumor was shown in the livers of the rats that were singly treated with a carcinogenic chemical-DEN. Foci of cellular alteration were observed in the livers of these rats. The proliferation lesions of liver from slight to seveity （foci of cellular aherationepatocelluar adenoma-hepatocellular carcinoma） were observed in the livers of the rats which exposed peros to a low dose of DEN for 90 days after initiation by a single intraperitoneal injection. The incidence of hepatocelluar tumor was 35% in male animal ,which was not shown in the liver of female rat. Conclusion：For current results, it may be possible that low-dose DEN acts as a promotor of hepatocelluar tumor if it was exposed in a population for a long time. It is considered that male hormone has a synergistic effect on hepatocelluar tumor development of DEN. This two-stage carcinogenesis test might be a new model for the study of drug induced and promoted carcinogenesis, which could be used to evaluate the carcinogenesis of chemical compound fast.

Nitrosamines crisis in pharmaceuticals-Insights on toxicological implications,root causes and risk assessment:A systematic review

The presence of N-nitroso compounds,particularly N-nitrosamines,in pharmaceutical products has raised global safety concerns due to their significant genotoxic and mutagenic effects.This systematic review investigates their toxicity in active pharmaceutical ingredients(APIs),drug products,and pharmaceutical excipients,along with novel analytical strategies for detection,root cause analysis,reformulation strategies,and regulatory guidelines for nitrosamines.This review emphasizes the molecular toxicity of N-nitroso compounds,focusing on genotoxic,mutagenic,carcinogenic,and other physiological effects.Additionally,it addresses the ongoing nitrosamine crisis,the development of nitrosamine-free products,and the importance of sensitive detection methods and precise risk evaluation.This comprehensive overview will aid molecular biologists,analytical scientists,formulation scientists in research and development sector,and researchers involved in management of nitrosamine-induced toxicity and promoting safer pharmaceutical products.

Health risk assessment of heavy metal pollution in groundwater of a karst basin,SW China

To investigate the presence of metal elements and assess their health risk for the populace in the Nandong Underground River Basin(NURB),we conducted an analysis of eleven common heavy metals in the water body.A Health risk assessment(HRA)model was employed to analyze 84 water samples from the NURB.The detection results revealed the following order of heavy metals concentrations:Fe>Al>Mn>Zn>As>Cd>Pb>Cr>Ni>Cu>Hg.Correlation analysis indicated a certain similarity in material source and migration transformation among these eleven metal elements.Our study identified that the health risks for local residents exposed to metal elements in the water of NURB primarily stem from carcinogenic risk(10^(−6)–10^(−4)a^(−1))through the drinking water pathway.Moreover,the health risk of heavy metal exposure for children through drinking water was notably higher than for adults.The maximum health risks of Cr in both underground and surface water exceeded the recommendation standard(5.0×10^(−5)a^(−1))from ICRP,surpassing the values recommended by the Swedish Environmental Protection Agency,the Dutch Ministry of Construction and Environment and the British Royal Society(5.0×10^(−6)a^(−1)).The results of the health risk assessment indicate that Cr in the water of NURB is the primary source of carcinogenic risk for local residents,followed by Cd and As.Consequently,it is imperative to control these three carcinogenic metals when the water was used as drinking water resource.

Contamination assessment,source apportionment and associated health risks of PTEs in agricultural soil under five land-use patterns in Sanya,China

To understand the levels of potentially toxic elements(PTEs)contamination in soils and their effects on human health from different agricultural land use in Sanya,China.128 soil samples(64 topsoil samples and corresponding subsoil samples)were collected from the five representative land-use patterns.Inductively coupled plasma mass spectrometry(ICP-MS),Atomic fluorescence spectrometry(AFS),and Inductively coupled plasma optical emission spectrometry(ICP-OES)were used to determine the content of PTEs(As,Cd,Hg,Cu,Cr,Ni,Pb,Zn,Co,Mo,Sb,and V).Correlation analysis and factor analysis were used to determine the source of PTEs.Geo-accumulation index(I_(geo)),hazard quotient(HQ),and total carcinogenic risk index(TR)were used to measure the PTEs contamination and its relative health impacts.Results showed that the average values of 12 PTEs in topsoil were higher than the Hainan soil geochemical baseline,showing different degrees of PTEs accumulation effect.The concentration of PTEs in the topsoil was lower than those in the subsoil except for Cd and Hg.The I_(geo)revealed that the major accumulated element in soils was As followed by Mo.Source apportionment suggested that parent materials and agricultural practices were the dominant factors for PTEs accumulation in the topsoil.Noncarcinogenic risks of soil samples from five land-use patterns presented a trend of paddy field>dry field>woodland>orchard>garden plot.However,the HQ values of 12 PTEs were less than the recommended limit of HQ=1,representing that there are no non-carcinogenic risks of PTEs for children and adults in the study area.The TR values are within 6.95×10^(-6)-1.38×10^(-5),which corresponds to the low level.Therefore the PTEs in the agricultural soil of the study area show little influence on the health status of the local population.

Health Impacts and Mechanisms of Per- and Polyfluoroalkyl Substances (PFAS) from Epidemiological to Toxicological

This research provides a comprehensive analysis of the health impacts of Per- and Polyfluoroalkyl Substances (PFAS) through an integration of epidemiological and toxicological studies. The study identifies significant correlations between PFAS exposure and adverse health outcomes, including thyroid dysfunction, elevated cholesterol levels, and increased risk of specific cancers. Utilizing a mixed-methods approach, the research combines a systematic review and meta-analysis of recent literature with in vitro and in vivo toxicological experiments. The epidemiological analysis reveals increased risks of thyroid dysfunction, cholesterol elevation, and certain cancers among PFAS-exposed individuals. Toxicological findings further corroborate these results, showing dose-dependent cytotoxic effects in human cell lines and endocrine disruption in rodent models. The study emphasizes the importance of regulatory measures to mitigate PFAS exposure and the urgent need for more comprehensive research into their long-term effects. The integration of epidemiological and toxicological data underscores the significant health risks posed by PFAS, highlighting the necessity of immediate action to limit exposure and develop safer alternatives.

The transcriptome analysis of cleft lip/palate-related PTCH1 variants in GMSM-K cells show carcinogenic potential

Cancer progression involves the sonic hedgehog(SHH)pathway,in which the receptor PTCH1 actives the downstream pathways.Dysfunction of PTCH1 can lead to nevoid basal cell carcinoma Syndrome(NBCCs)including neoplastic disease and congenital disorder.To evaluate the relationship between PTCH1 and cancer,we applied the CRISPR/Cas9 system to knock out PTCH1 in oral nontumorous epithelial cells(GMSM-K).Then we screened six PTCH1 variants associated with cleft lip/palate(CL/P),one of the congenital disorders in NBCCs,and generated PTCH1 variant and wild-type recombinant PTCH1^(−/−)GMSM-K cell lines.Transcriptome sequencing was conducted in these cell lines.The results revealed that differentially expressed genes(DEGs)in PTCH1^(−/−)GMSM-K were enriched in extracellular compartments,contributing epithelial diseases by pathway enrichment analysis.RT-PCR confirmed that KRT34,KRT81,KRT86,PDGFB,and WNT10B genes,associated with extracellular compartments were highly expressed in PTCH1^(−/−).The Kyoto Encyclopedia of Genes and Genomes analysis also suggested that DEGs are closely related to focal adhesion,transcriptional misregulation,and proteoglycans in breast and gastric cancers.Comparative analysis of samples revealed that the CL/P-associated PTCH1 variants A443G and V908G are potentially carcinogenic.These findings provide new insights into the carcinogenic potential of PTCH1 dysfunction.

Impact of mycotoxins and their metabolites associated with food grains

Mycotoxins are secondary toxic metabolites synthesized by numerous filamentous fungi including members of the genus Fusarium,Penicillium,Drechslera,Aspergillus,Claviceps,Monascum,Alternaria,Cephalosporium,Nigrospora,and Trichoderma.Among them,Aspergillus and Fusarium species are major plant pathogens recognized to induce infection and produce mycotoxins in food crops.More than 400 mycotoxins have been documented and among them,aflatoxin,fumonisins,trichothecenes,zearalenone,ochratoxin A,citrinin,ergot alkaloids,and patulin are the most prominent compounds linked to a variety of human and animal health disorders.Genus Fusarium and Aspergillus belong to a saprophytic group,which can infect and contaminate many crops at pre and post-harvest stages.Mycotoxins can have a variety of negative effects on health in both humans and animals.Mycotoxins and their metabolites can cause severe acute poisoning,which can result in death,as well as long-term negative health effects,such as cancer and immune-suppressive disorders in living beings(animals and humans).Mycotoxin contamination of agricultural goods has gained global significance,due to its toxic effects on living beings,as well as its importance to international trade.Our objective is to provide a consolidated information on the potential mycotixs in food grains and their significant impact on the health of the human beings.

Human Health Risks from Exposure to Heavy Metals of Suspended Particulate Matter around the Tongon Gold Mine, Côte d’Ivoire

The Tongon mine, the largest gold mine in C?te d’Ivoire, has been in operation since April 2010. However, to our knowledge to date, no study has been conducted on metallic contamination in suspended particulate matter (PM10 and PM2.5) where there is a lack of information on the carcinogenic and non-carcinogenic risk to human health associated with the exposure of populations in the Tongon area to these pollutants. The general objective of this study is to evaluate the level of contamination of PM10;PM2.5 by heavy metals and their impact on the health of populations exposed to these pollutants in the Tongon gold mine area. The sampling and measurement of suspended particulate matter (PM10 and PM2.5) were done using a MiniVol TAS passive air sampler. Heavy metal concentrations were determined by inductively coupled plasma mass spectroscopy (Nex ION 2000 ICP-MS, USA). The results indicate that the average concentrations of suspended particles (PM2.5 and PM10) obtained are all above the recommended exposure limits. In addition, among the heavy metals contained in the suspended particles, the concentrations of arsenic and nickel are high and all above the standard limit values. The assessment of the health risks related to the inhalation of PM10 particles reveals that their inhalation over a long period could cause a carcinogenic risk.

Experimental and clinic-opathologic study on the relationship between transcription factor Egr-1 and esophageal carcinoma

AIM: To observe the growth suppression effect of exogenous introduction of early growth response gene-1 (Egr-1 gene) on esophageal carcinoma tissue as well as on esophageal carcinoma cell line Eca109 and to explore the potential application of Egr-1 gene in gene therapy of tumor. METHODS: Eukaryotic expression vector of PCMV-Egr-1 plasmid was introduced into Eca109 cell line which expressed no Egr-1 protein originally with lipofectamine transfection method. The introduction and expression of PCMV-Egr-1 plasmid into Eca109 cell line was confirmed by G418 selection culture, PCR amplification of neogene contained in the vector, Western blot analysis and immunocytochemical analysis. The cell growth curve, soft agar colony formation rate and tumorigenicity in SCID mice were examined to demonstrate the growth suppression effect of exogenous Egr-1 gene on Eca109 cell line. The Egr-1 mRNA and Egr-1 protein were also detected in 50 surgical specimens of esophageal carcinoma by in situ hybridization and immunohistochemistry. RESULTS: Exogenous Egr-1 gene was introduced successfully into Eca109 cell line and expressed Egr-1 protein stably. The transfected Eca109 cell line grew more slowly than control Eca109 as shown by cell growth curves, the soft agar colony formation rate (4.0% vs 6.9%, P 【 0.01) and the average growth rate of tumor in SCID mice (35.5 +/- 7.6 vs 65.8 +/- 7.6, P 【 0.05). The expression level of Egr-1 mRNA and protein significantly increased in dysplastic epithelia adjacent to cancer rather than in cancer tissues (65.8% vs 20.0% by ISH and 57.9% vs 0.01). CONCLUSION: Exogenous Egr-1 gene shows the strong effect of growth inhibition in Eca109 cell line. Egr-1 in the cancer tissue shows down-regulated expression that supports the inhibited function of Egr-1 in cancer growth and suggests Egr-1 may have an important role in gene therapy of esophageal carcinoma.

Effect of 5-Aza-2'-deoxycytidine on the P16 tumor suppressor gene in hepatocellular carcinoma cell line HepG2

INTRODUCTIONHepatocellular carcinoma (HCC) is one of the mostcommon human malignancies worldwide[1,2], and isclosely associated with infection of HBV and HCVand contamination of aflatoxin B1[3-6]. Althoughthe molecular mechanisms of hepatocarcinogenesisremain poorly understood, an increasing number ofgenetic abnormalities have been recognized[7-10],for example, the p16 gene[11,12] the p53gene[13-18], the E-cadherin gene[19], and the c-mycgene[20].

Relationship between Structures and Carcinogenicities of Heterocyclic Amines

Semi-empirical molecular orbital calculations were performed on heterocyclic aromatic amines(HCAs). The relationship between the structures and the carcinogenicities can be rationally elucidated by the models based on the metabolism of HCAs and the Di-region theory. The degree of easiness for the formation of Di-region electrophilic centers determines the carcinogenic activity. There is a good linear relationship between the observed carcinogenicities and the PM3 calculated parameters, with r=0.973 and F=29.8>F ** 0.01 .

Synoptic Analysis of Epidemiologic Evidence of Brain Cancer Risks from Mobile Communication

In the radio frequency (RF) range concern about long-term health risks from electromagnetic fields (EMF) is enhanced by contradictory results and conclusions from epidemiologic studies. A new approach of a synoptic analysis of all available data from epidemiological studies published since 2001 was performed. This approach provided new insight with regard to a potential link between mobile phone use and brain cancer. Two quite different data pools could be identified with numerous studies from one research group opposing all other studies. However, it could be shown that with the number of exposed cases both data pools exhibit a clear trend of risk estimates (odds ratios) towards the final result, namely a reduced cancer risk of OR = 0.8, though from either side of the zero-risk line. The analysis of potential long-term effects indicated by a dosedependence revealed diverging results with different dose metrics. Overall, the synoptic analysis supports reassuring rather than alarming conclusions on RF EMF health risks from mobile telecommunication.

In silico assessment of human health risks caused by cyanotoxins from cyanobacteria

Harmful algal blooms(HABs)that are formed by cyanobacteria have become a serious issue worldwide in recent years.Cyanobacteria can release a type of secondary metabolites called cyanotoxins into aquatic systems which may indirectly or directly provide health risks to the environment and humans.Cyanotoxins provide some of the most powerful natural poisons including potent neurotoxins,hepatotoxins,cytotoxins,and endotoxins that may result in environmental health risks,and long-term morbidity and mortality to animals and humans.In this research,we used the chemcomputational tool Molinspiration for molecular property predictions,Pred-hERG 4.2 web software for cardiac toxicity prediction,and Pred-Skin 2.0 web software for predicting skin sensitization.We are predicting some toxicological aspects of cyanobacteria here using chemcomputational tools with the hypothesis that cyanotoxins are providing a risk to human health.We are using the tool Pred-hERG 4.2 to predict hERG channel blocking potential and the Pred-skin tool to predict skin sensitization due to cyanotoxins.The potential of anatoxin,ambigol,the microcystin group,and lyngbyatoxin A,lyngbyatoxin B,nodularin-R,and saxitoxin were predicted to cause skin sensitization in the final results(consensus model).Anatoxin-a and lyngbyatoxin were predicted to allow GI absorption and blood–brain barrier penetration.Among the 20 predicted cyanotoxins only aeruginosin 103-A,ambigol A,and ambigol were predicted by Pred-hERG 4.2 according to the applicability domain results as potential cardiotoxins with weak or moderate potency.Lyngbyatoxin shows activity through the GPCR ligand and protease,kinase,and enzyme inhibitor.