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.

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.

Dietary Intake, Carcinogenic and Non-Carcinogenic Risk Potentials of Lead, Cadmium, Mercury and Arsenic Exposure via Consumption of Dried Crayfish in Calabar, Nigeria

Intense pressure from both onshore and offshore oil exploration and exploitation activities, together with the accompanying urbanization and industrialization has resulted in massive contamination of land and water resources in Niger Delta, Nigeria. Whereas crayfish is very sensitive to contaminant in the aquatic environment and constitute an important part of human diet, its quality and safety from environmental pollutant is of serious health concern. Evaluation of dietary intake, potential carcinogenic and non-carcinogenic risk of lead, cadmium, mercury and arsenic exposure via consumption of dried crayfish purchased from major markets in Calabar, Nigeria was carried out between June and August 2021. Thirty-six composite samples of dried crayfish purchased from 180 vendors were used for the study. Heavy metals concentrations were determined using Atomic Absorption Spectrophotometer (Model AA-6800, Japan) after wet digestion. Metals concentrations (Mg/kg) were of the ranges 0.02 - 0.24, 0.14 - 0.86, 0.32 - 0.72, 0.04 - 0.19 for Pb, Cd, Hg and As respectively. The mean content of cadmium and mercury exceeded FAO/ WHO and Commission of European Communities maximum levels for crustaceans. Average Estimated Daily Intake for each of the metals was found to be above the recommended daily intake level except for arsenic. The average estimated daily intake values for Cd and Hg were also above the tolerable upper intake level. Average Target Hazard Quotient of all the metals and Hazard Index of all the markets were below 1.00. The Incremental Lifetime Cancer Risk of the metals was greater than the standard tolerable regulatory risk (10-4) for carcinogens. Consumption of crayfish purchased from major markets in Calabar could pose a range of carcinogenic and non-carcinogenic human health risks.

Maternal and Fetal Exposure to Four Carcinogenic Environmental Metals

Objective To examine maternal and fetal exposure levels to four carcinogenic metals, arsenic （As）, cadmium （Cd）, nickel （Ni）, and beryllium （Be）, and to investigate their environmental influences. Methods Metal concentrations in maternal and umbilical cord blood were measured by inductively coupled plasma-mass spectrometry （ICP-MS）. Environmental factors that might play a role in exposure were analyzed using Mann Whitney nonparametric U-tests and multiple linear regression. Results The concentrations of As, Cd, and Ni in umbilical cord blood （5.41, 0.87, and 139.54 gg/L） were significantly lower than those in maternal blood （6.91, 1.93, and 165.93 p.g/L）. There were significant positive correlations between the maternal and cord concentrations of each carcinogen. Our results showed that： （i） exposures to potentially harmful occupational factors during pregnancy were associated with high levels of maternal As, Cd, and Ni; （ii） living close to major transportation routes （〈500 m） or exposure to second-hand smoke during pregnancy increased the maternal Cd levels and （iii） living close to industrial chimneys induced high maternal Ni levels. Multiple linear regression analysis showed that these environmental factors remained significant in models of the influences of these four carcinogens. Conclusion Both mothers and fetuses had been exposed to As, Cd, Ni, and Be. The increased levels of these carcinogens in pregnant women were associated with some detrimental environmental factors, such as occupational exposure, contact with second-hand smoke and living close to major transportation routes or industrial chimneys.

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.

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.

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 .

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.

Activation of Carcinogenic Non-aminoazo Compounds in Horseradish Peroxidase/H_2O_2 System

Eriochrome black T and Nitrosulfophenol S were advocated as the chemical models of carcinogenic non-aminoazo compounds. The main products of their oxidative cleavage in horseradish peroxidase/H2O2 system was identified as the benezenediazonium ion, the ultimate carcinogens, which could bind to DNA. The reaction conditions were investigated preliminarily. Some inhibitors and inducers of the reaction were discovered.

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.

Levels of Genotoxic and Carcinogenic Ingredients in Plant Food Supplements and Associated Risk Assessment

The present study describes the selection, analysis and risk assessment of genotoxic and carcinogenic ingredients of botanicals and botanical preparations which can be found in food and plant food supplements (PFS). First an inventory was made of botanical ingredients that are of possible concern for human health because of their genotoxic and/or carcinogenic properties. In total, 30 botanical ingredients were selected and subsequently judged for their actual genotoxic and/or carcinogenic potential. Among the 30 compounds considered, 18 compounds were judged to be both genotoxic and carcinogenic. Interestingly, the majority of these compounds belong to the group of alkenylbenzenes or unsaturated pyrrolizidine alkaloids. Subsequently, based on available carcinogenicity data and estimated daily human exposure that was determined focusing on the intake from PFS, the Margin of Exposure (MOE) was calculated for the alkenylbenzenes estragole, methyleugenol, safrole and β-asarone. Calculating the MOEs for intake estimates of these alkenylbenzenes from PFS resulted in MOE values that were generally lower than 10,000 and often lower than 100. In some cases the MOE was even below 10 meaning that the estimated daily intake is in the range of dose levels causing malignant tumors in experimental animals. This result indicates that the use of PFS containing the genotoxic carcinogens estragole, methyleugenol, safrole or β-asarone might raise a potential concern for human health and would be of high priority for risk management.

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 Uniform Carcinogenic Action of Alkylnitrosoureas in Syrian Hamsters

The carcinogenic effects of a number of alkylnitrosoureas in Syrian golden hamsters have been compared by administering them by gavage as solutions in corn oil/ethyl acetate.The compounds were methyl-,ethyl-,2-hydroxyethyl-,2-oxopropyl-,and 2-phenylethylnitrosourea and the dialkylnitrosoureas dimethyl- and diethylnitrosourea,ethylnitrosohydroxyethylurea, ethylnitroso-2-oxopropylurea,2-oxopropylnitrosochloroethylurea,and hydroxyethylnitroso- ethylurea.All were given at approximately equimolar doses and,in most cases,to male and female hamsters.Most of the hamsters died with tumors associated with the treatments.Methyl- nitrosourea,ethylnitrosourea,and hydroxyethylnitrosourea,but not oxopropylnitrosourea, gave rise to a high incidence of tumors of the forestomach,while the dialkylnitrosoureas pro- duced smaller numbers of forestomach tumors.All of the alkylnitrosoureas induced hemangio- sarcomas of the spleen,which was the most common tumor produced by these carcinogens. Tumors of other types were uncommon,except that ethylnitrosourea and ethylnitrosohydroxy- ethylurea induced tumors of the cervix in about half of the animals and ethylnitrosooxopropyl- urea induced some nervous system tumors.The small number of common target organs of alkylnitrosoureas in hamsters contrasted sharply with the broad spectrum of tumors they in- duced in rats,depending on the nature of the alkyl groups,and with a quite different order of potency in the latter species,1989 Academic Press.Inc.

Hemoglobin Adducts as Biomarkers of Exposure to and metabolic Activation of Carcinogenic Tobacco-Specific Nitrosamines

The carcinogenic tobacco-specific nitrosamines N-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-l-(3-pyridyl)-l-butanone (NNK) form hemoglobin adducts in laboratory animals and humans. These adducts release 4-hydroxy-l-(3-pyridyl)-l-butanone (HPB) upon mild base hydrolysis. HPB released from human hemoglobin can be quantified by gas chromatography-mass spectrometry. It is the only available biochemical marker for determination of exposure to, and metabolic activation of, carcinogens present only in tobacco. Levels of HPB were highest in snuff-dippers, followed by smokers and nonsmokers. Large interindividual variations in adduct levels were observed. The relationship between HPB levels in globin and DNA of rats treated with NNK has been investigated in order to aid in interpretation of the data from humans. These studies have provided the initial database for understanding the metabolic activation of tobacco-specific nitrosamines in humans.

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.

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.

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.

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.

Health Risk Assessment on Drinking Water in Shenzhen, China

Objectives: To conduct health risk assessment on drinking water in 2012 in Shenzhen of China. Methods: The water quality monitoring data on product water and pipe water in 2012 were collected and analyzed, and the risk evaluation models recommended by the U.S. environmental protection agency (US EPA) were employed, to perform adults and children’s health risk assessments on the three kinds of genetic toxic substances such as hexavalent chromium, cadmium and arsenic and the 12 non-carcinogenic materials such as iron, manganese, lead, fluoride, volatile phenol, cyanide, mercury, ammonia nitrogen, nitrate, copper, zinc and selenium. Results: The results about water quality from the 150 factory samples and 207 peripheral water samples showed that the measured indicators in other water samples were accord with the National Health Standards (GB5749-2006) released by Ministry of Health of the People’s Republic of China, except manganese level in one factory sample and the same index in one peripheral sample, and nitrate concentration in another water sample were out of limit, respectively. Namely, the total of 3 samples was disqualification. The adults and children’s health risks (HI) on the 12 non-carcinogenic materials were 178.04 × 10-8 and 249.96 × 10-8 in the factor water samples, and 363.02 × 10-8 and 509.66 × 10-8 in the pipe samples, respectively. Lead in factory water and fluoride in peripheral water samples were the most serious harm in the all measured non-carcinogenic indicators. The adults and children’s cancer risks (R) on the 3 genetic toxic substances were 25.60 × 10-6 and 28.51 × 10-6 in the factor water samples, and 23.47 × 10-6 and 26.08 × 10-6 in the pipe samples, respectively. Hexavalent chromium was the most damage among the three detected carcinogenic indicators. Therefore, the total adults and children’s health hazard risks including the 3 carcinogenic and 12 non-carcinogenic substances were 27.38 × 10-6 and 31.00 × 10-6 in the factor water samples, and 27.10 × 10-6 and 31.17 × 10-6 in the pipe samples, respectively. Genetic toxic matters in drinking water are the main hazard and more children’s health risk than adults’ risk. Conclusions: The health risk (R) on the 15 kinds of chemicals in Shenzhen’s municipal water supply was in the range of maximum acceptable risk levels (5.0 × 10-5/a) recommended by the International Commission of Radiation Protection (ICRP). The results in this study indicate that the carcinogenic substances are greater risk comparing with the non-carcinogenic substances, and hexavalent chromium is the biggest carcinogenic risk, and lead and fluoride are the most non-carcinogenic risk, and the rather risk of children than adults.