Non-carcinogenic Chemicals Research Articles

Occupational health risks of VOCs emitted from the working face of municipal solid waste landfill: Temporal variation and influencing factors.

Volatile organic compounds (VOCs) emission on the working face of a large sanitary landfill in northern China was characterized in a one-year long sampling campaign. A total of 67 VOCs with average annual concentration of 2903.01μg/m3 were detected. Ethanol was the dominant species of detected VOCs, accounting for 76.4-82.3% of the total volatile organic compounds (TVOCs) concentration. VOCs emission showed seasonal variation as the highest concentration was detected in summer and lowest appeared in winter. Furthermore, 50 VOCs identified were non-carcinogenic chemicals and 21 of them were carcinogenic chemicals. Risk assessment showed that the average total non-carcinogenic risk value (HIT) was 4.95, which far exceeded the threshold value of 1; and the average total carcinogenic risk value (RiskT) was 8.45×10-5, close to the limit of 1×10-4. That means both the non-carcinogenic and carcinogenic risks of long-term exposure to these VOCs could not be ignored. Some of the oxygenated compounds (Acrolein, Ethyl acetate, etc.), halocarbons (1,1,2-Trichloroethane, 1,2-Dichloropropane, etc.) and aromatic compounds (Naphthalene, m+p-Xylene, etc.) consisted the main contributors to non-carcinogenic risks. Meanwhile, carcinogenic risks were mainly caused by halocarbons (cis-1,2-Dichloroethylene, FREON11, etc.) and aromatic compounds (Benzene, Ethylbenzene, etc.). In addition, statistical analysis revealed that the HIT values were related to the concentrations of risk aromatic compounds, halocarbons and hydrocarbons; RiskT values were only related to the concentrations of risk aromatic compounds and halocarbons. The research results provide an important theoretical basis for occupational risk management and VOCs emission prevention in landfills.

Risk Assessment of Heavy Metal in Farmlands and Crops Near Pb–Zn Mine Tailing Ponds in Niujiaotang, China

To accurately evaluate the pollution and risk of heavy metals in crops and farmlands near mines, we determined the contents of Cr, Ni, Cu, As, Cd, Pb, and Zn in 10 farmland soil sampling sites and six crops (pak choi, rice, spring onion, radish, Chinese cabbage, Chrysanthemum coronarium) in an area near the Niujiaotang Pb-Zn mine in Duyun City, China. Four evaluation methods were compared, including the potential ecological hazard index, Nemeiro comprehensive pollution assessment, risk assessment code, and the ratio of secondary phase to primary phase methods. The average concentration of As, Cd, Pb, and Zn exceeded the soil environmental background levels in Niujiaotang and Guizhou Province. Cd exceeded the standard substantially, and Zn pollution accumulation was the most evident. Heavy metal contamination of crops was in the order pak choi > Chinese cabbage > spring onion > paddy > radish > Chrysanthemum coronarium, whereas heavy metal concentration in crops were in the order Zn > As > Cr > Cd > Ni > Pb. The levels of all heavy metals except Cu exceeded Chinese food hygiene standards. Carcinogenic and non-carcinogenic chemicals in crops present significant risks to adults and children. Risk evaluation considering the morphological contents of heavy metals rather than their total concentration was more accurate for environmental quality assessment of agricultural soils. Samples should be collected at different times to study the spatial and temporal distribution, and further studies on the migration transformation of heavy metals between the tailings pond-soil-crop should be conducted.

Estimation of Human Health Risk Due to Heavy Metals around Schools and Auto-Mobile Workshops near Frequented Roads in Kaduna State, Nigeria

Heavy metals are widely known for their potential to cause carcinogenic and non-carcinogenic health risks. In this work, the carcinogenic and non-carcinogenic health risks associated with heavy metals in the vicinity of schools and auto mechanic workshops close to busy roads in Kaduna state was assessed using NEX CG EDXRF MODEL with brand name RIGAKU situated at a UTM Laboratory, Malaysia. The obtained heavy metals concentrations were used to estimate the health effects that might result from exposure to carcinogenic and non-carcinogenic chemicals for both the population ages using US EPA methodology. Findings indicated that in some locations the carcinogenic and non-carcinogenic hazards associated with exposure for residents was greater than the US EPA acceptable thresholds of 10-4 and 1 respectively. This indicated that the heavy metals may result to unacceptable carcinogenic and non-carcinogenic risks, which is an issue of concern in public health especially looking at the way school children play around these areas. The present study therefore provides scientific basis for strategies required to protect human and environmental health in schools and automobile workshops.

КАНЦЕРОГЕННЫЙ И НЕКАНЦЕРОГЕННЫЙ РИСК ДЛЯ НАСЕЛЕНИЯ ОТ ПОТРЕБЛЕНИЯ КАРТОФЕЛЯ И ОВОЩЕЙ, ВЫРАЩИВАЕМЫХ В ПРЕДЕЛАХ АГРОСЕЛИТЕБНЫХ ЛАНДШАФТОВ

One of the most effective methods of preventing the danger caused by the impact of carcinogenic and non-carcinogenic chemicals on humans is to establish the risk of undesirable effects in order to further development methods to minimize it. The purpose of this study is to establish the magnitude of the non-carcinogenic and carcinogenic risk caused by the intake of heavy metals when consuming potatoes and vegetables grown within the agro-residential landscapes of Gorki, as well as when contaminants enter the human body by the oral, inhalation and percutaneous route directly from the soil. It has been established that the maximum contribution to the exposure of Cu, Zn, Mn and Cd entering the body of the adult population of the city of Gorki is made by beetroot, potatoes and white cabbage. Table carrots and potatoes make the maximum contribution to the exposure of Cu and Cd for the child population, while the main sources of Zn, Mn, and Pb intake are potatoes and white cabbage. The total level of carcinogenic risk from the consumption of potatoes and vegetables due to such carcinogens as Pb and Cd is estimated as average according to the international criterion scale. The non-carcinogenic risk to the health of both adults and children due to inhalation, oral and percutaneous intake of heavy metals from contaminated soil is assessed as negligible, and the carcinogenic risk is at an acceptable level. The results of the studies performed can be used to develop a risk management strategy for the population due to pollution of urban soils, potatoes and vegetables with heavy metals, providing for the sequential passage of the following stages: comparative assessment and ranking of risk; determination of risk acceptability levels; risk reduction and control; response to risk.

대학 실험실에서의 유기화합물 노출에 의한 건강위험성 평가에 관한 연구

Objectives: Laboratories have various latent physical, chemical, biological, and ergonomical factors according to the diversification and fusion of research and development activities. This study aims to investigate the chemical exposure concentrations of college laboratories and evaluate their health risks, and use them as basic data to promote the health of college students. Methods: The sampling and analysis of harmful chemicals in the air in laboratories were performed using Method 1500 of the U.S. National Institute for Occupational Safety and Health (NIOSH)의 Method 1500. The harmful chemicals in the laboratories were divided into carcinogenic and non-carcinogenic chemicals. Risk assessment was performed using the cancer risk (CR) for carcinogenic chemicals and using the hazard index (HI) for non-carcinogenic chemicals. Results: The harmful chemicals in college laboratories consisted of acetone, diethyl ether, methylene chloride, n-hexane, ethyl acetate, chloroform, tetrahydrofuran, toluene, and xylenes. They showed the highest concentrations in laboratories A (acetone 0.001~2.34ppm), B (chloroform 0.95~6.35ppm), C (diethyl ether 0.08~8.68ppm), and D (acetone 0.07~14.96ppm). The risk assessment result for non-carcinogenic chemicals showed that the HI of methylene chloride was 2.052 for men and 2.333 for women, the HI of N-hexane was 4.442 for men and 5.05 for women. Thus, the HI values were higher than 1. The risk of carcinogenic chemicals is determined by an excess cancer risk (ECR) value of 1.0x10-5, which means that one in 100,000 people has a cancer risk. The ECRs of chloroform exceeded 1.0x10-5 for both men and women, indicating the possibility of cancer risk. Conclusion: College laboratories showed the possibility of non-carcinogenic health risks for methylene chloride, n-hexane, tetrahydrofuran (THF), toluene, and xylenes, and carcinogenic health risks for chloroform, methylene chloride. However, this study used the maximum values of measurements to determine the worst case, and assumed that the subjects were exposed to the corresponding concentrations continuously for 8 hours per day for 300 days per year. In consideration of the nature of laboratory environment in which people are intermittently exposed, rather than continuously, to the chemicals, the results of this study has an element of overestimation.

Identification of Carcinogenic Chemicals with Network Embedding and Deep Learning Methods

Background: Cancer is the second leading cause of human death in the world. To date, many factors have been confirmed to be the cause of cancer. Among them, carcinogenic chemicals have been widely accepted as the important ones. Traditional methods for detecting carcinogenic chemicals are of low efficiency and high cost. Objective: The aim of this study was to design an efficient computational method for the identification of carcinogenic chemicals. Methods: A new computational model was proposed for detecting carcinogenic chemicals. As a data-driven model, carcinogenic and non-carcinogenic chemicals were obtained from Carcinogenic Potency Database (CPDB). These chemicals were represented by features extracted from five chemical networks, representing five types of chemical associations, via a network embedding method, Mashup. Obtained features were fed into a powerful deep learning method, recurrent neural network, to build the model. Results: The jackknife test on such model provided the F-measure of 0.971 and AUROC of 0.971. Conclusion: The proposed model was quite effective and was superior to the models with traditional machine learning algorithms, classic chemical encoding schemes or direct usage of chemical associations.

MODERN APPROACHES OF ESTIMATION OF RISK FACTORS INTERMITTENT INFLUENCE

We studied the quality of three environmental objects of the population living in a large industrial city (atmospheric air, soil and drinking water). We also determined the content and quantity of chemicals in the habitat of the population living near large industrial enterprises. We presented the results of the calculations of hazard indexes (HI), on the basis of which we derived the risk features of the development of non-carcinogenic effects of exposure to the body of chemical compounds (with combined and complex exposure). Non-carcinogenic risk is defined as an indicator of the expected increase in the incidence of the population due to the toxic properties of foreign chemicals in the studied environmental objects. The main objective of our socio-hygienic study was to identify chemical factors in the environment that are potentially hazardous to the life and health of children and adults living within a radius of 4,800 meters from an industrial enterprise in a large industrial city when received in different ways (combined) and assess the risk of violations in human health of varying severity when exposed to non-carcinogenic chemicals

Effect of aflatoxin B1, benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells

The increasing number of man-made chemicals in the environment that may pose a carcinogenic risk highlights the need for developing reliable time- and cost-effective approaches for carcinogen detection and identification. To address this issue, we investigated the utility of high-throughput microarray gene expression and next-generation genome-wide DNA methylation sequencing for the in vitro identification of genotoxic and non-genotoxic carcinogens. Terminally differentiated and metabolically competent human liver HepaRG cells were treated at minimally cytotoxic concentrations of (i) the genotoxic human liver carcinogen aflatoxin B1 (AFB1) and its structural non-carcinogenic analog aflatoxin B2 (AFB2); (ii) the genotoxic human lung carcinogen benzo[a]pyrene (B[a]P) and its non-carcinogenic isomer benzo[e]pyrene (B[e]P); and (iii) the non-genotoxic liver carcinogen methapyrilene for 72 h and transcriptomic and DNA methylation profiles were examined. Treatment of HepaRG cells with the liver carcinogens AFB1 and methapyrilene generated distinct gene-expression profiles, whereas B[a]P had only a slight effect on gene expression. In contrast to transcriptomic alterations, treatment of HepaRG cells with the carcinogenic and non-carcinogenic chemicals resulted in profound changes in the DNA methylation footprint; however, the correlation between gene-specific DNA methylation and gene expression changes was minimal. Among the carcinogen-altered genes, transferrin (TF) emerged as sensitive marker for an initial screening of chemicals for their potential liver carcinogenicity. Potential liver carcinogens (i.e., chemicals causing altered TF gene expression) could then be subjected to gene-expression analyses to differentiate genotoxic from non-genotoxic liver carcinogens. This approach may substantially enhance the identification and assessment of potential liver carcinogens.

Analysis of key GO terms and KEGG pathways associated with carcinogenic chemicals.

Cancer is one of the serious disease that causes several human deaths every year. Up to now, we have spent lots of time and money to investigate this disease, thereby designing effective treatments. Previous studies mainly focus on studying genetic background of different subtypes of cancer and neglect another important factor, environmental factor. Carcinogenic chemical is one of the type of environmental factor, exposure of such chemical may definitely initiate and promote the tumorigenesis. In this study, we tried to partly describe the differences between carcinogenic and non-carcinogenic chemicals using gene ontology (GO) terms and KEGG pathways. The carcinogenic and non-carcinogenic chemicals that were retrieved from Carcinogenic Potency Database (CPDB) were encoded into numeric vectors using the enrichment theories of GO terms and KEGG pathways. Then, the minimal redundancy maximal relevance (mRMR) method was adopted to analyze all features, resulting in some important GO terms and KEGG pathways. The extensive analysis of the identified GO terms and KEGG pathways indicate that they all play roles during the tumorigenesis, inducing that they can be key indicator for identification of carcinogenic chemicals.

Acylamino acid chiral fungicides on toxiciepigenetics in lambda DNA methylation

Acylamino acid chiral fungicides (AACFs) are low-toxicity pesticides and considered as non-carcinogenic chemicals to laboratory animals. Though AACFs have potential toxicological effects on mammals by non-genotoxic mechanisms, the toxicoepigenomics of AACFs has not been documented. In this article, we explored toxiciepigenetics of metalaxyl, benalaxyl and furalaxyl through epigenetics research on lambda DNA under different concentration exposure. The toxicoepigenomic difference of stereoisomers was examined also. Our results showed that AACFs would affect methyltransferase activity resulting in modulating DNA methylation levels and pattern. The LOAEL of R-metalaxyl and S-metalaxyl were 30 mM and 0.3 mM, respectively. The LOAEL of (R, S)-benalaxyl and (R, S)-furalaxyl were 0.3 Mm and 30 mM, respectively. A significant dose-response effect between (R, S)-benalaxyl and global methylation level was observed. Global methylation level was more susceptible to S-enantiomer compared to R-enantiomer, which indicated enantiomers of AACFs have the enantioselectivity in toxiciepigenetics. Moreover, the dependence of the methylation inhibition on the chiral center of metalaxyl may suggest a considerable specificity of the compound of AACFs for DNA methyltransferases. The inhibition effect between R-enantiomer and S-enantiomer of AACFs on DNA methylation levels generated in this study is important for low-toxicity pesticides toxicoepigenomics evaluation.

Discriminating between adaptive and carcinogenic liver hypertrophy in rat studies using logistic ridge regression analysis of toxicogenomic data: The mode of action and predictive models

Chemical exposure often results in liver hypertrophy in animal tests, characterized by increased liver weight, hepatocellular hypertrophy, and/or cell proliferation. While most of these changes are considered adaptive responses, there is concern that they may be associated with carcinogenesis. In this study, we have employed a toxicogenomic approach using a logistic ridge regression model to identify genes responsible for liver hypertrophy and hypertrophic hepatocarcinogenesis and to develop a predictive model for assessing hypertrophy-inducing compounds. Logistic regression models have previously been used in the quantification of epidemiological risk factors. DNA microarray data from the Toxicogenomics Project-Genomics Assisted Toxicity Evaluation System were used to identify hypertrophy-related genes that are expressed differently in hypertrophy induced by carcinogens and non-carcinogens. Data were collected for 134 chemicals (72 non-hypertrophy-inducing chemicals, 27 hypertrophy-inducing non-carcinogenic chemicals, and 15 hypertrophy-inducing carcinogenic compounds). After applying logistic ridge regression analysis, 35 genes for liver hypertrophy (e.g., Acot1 and Abcc3) and 13 genes for hypertrophic hepatocarcinogenesis (e.g., Asns and Gpx2) were selected. The predictive models built using these genes were 94.8% and 82.7% accurate, respectively. Pathway analysis of the genes indicates that, aside from a xenobiotic metabolism-related pathway as an adaptive response for liver hypertrophy, amino acid biosynthesis and oxidative responses appear to be involved in hypertrophic hepatocarcinogenesis. Early detection and toxicogenomic characterization of liver hypertrophy using our models may be useful for predicting carcinogenesis. In addition, the identified genes provide novel insight into discrimination between adverse hypertrophy associated with carcinogenesis and adaptive hypertrophy in risk assessment.

Lifetime of positronium in carcinogenic and noncarcinogenic chemicals

The presence or lack of carcinogenic properties of substances is investigated by positron annihilation spectroscopy. This method is based on the electrophilic nature of carcinogens and the sensitivity of positron annihilation lifetime spectroscopy, that is, a change in the lifetime of positronium depending on the electron density of a medium. We consider differences in the annihilation time of certain synthetic and natural dyes. The obtained data are compared with the boundary value of the positronium lifetime, separating all the substances under investigation into carcinogens and noncarcinogens.

Abstract 4580: Expression of γH2AX as a biomarker of genotoxic carcinogen in the urinary bladder of rats

Abstract Background: Bladder cancer is the seventh most common cancer in males worldwide. Recent studies have demonstrated that DNA double-strand breaks are recognized to be a serious injury leading to genome instability and cancer development. The rapid phosphorylation of histone H2AX at Serine 139, to become γH2AX, occurs in response to DNA double-strand breaks. Roles of γH2AX in carcinogenesis are still unclear, and there are few reports on the association with bladder cancer. We have previously demonstrated that γH2AX expression is induced in urinary bladders of N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-treated rat (Toyoda et al., J Toxicol Pathol, 26: 215-221, 2013). To evaluate the value of γH2AX as a biomarker for carcinogenicity and genotoxicity to the urinary bladder, we performed an immunohistochemical analysis of γH2AX expression in chemical-treated rats. Methods: Six-week-old male F344 rats were treated with 0.05% BBN, 1.8% 2-nitroanisole (2-NA), 2% 2,2-bis (bromomethyl)-1,3-propanediol (BMP), 0.1% phenethyl isothiocyanate (PEITC), 3% melamine, or 3% uracil in either drinking water (BBN) or diet (other chemicals) for 4 weeks. Animals were sacrificed at 4 or 6 weeks of the experiment, and immunohistochemistry for γH2AX in urinary bladders was performed. Results: At week 4, γH2AX expression in the urothelium were significantly increased in BBN and 2-NA groups compared with the controls. γH2AX expression ratio (positive cells/1000 cells) in BBN, 2-NA and control groups were 76±21, 111±37 and 0.8±0.6, respectively. γH2AX was recognized as dot-like foci in nuclei of epithelial cells, and the positive cells were mainly located near the basal layer of the mucosa. In BMP and PEITC groups, γH2AX expression was mainly observed in umbrella cells and intermediate cells, respectively. In melamine and uracil groups, there were diffuse urothelial hyperplasia and focal expression of γH2AX especially in the basal layer. The expression ratios of γH2AX in BMP, PEITC, melamine and uracil groups were 8.3±6.6, 26±9.0, 16±11 and 11±11, respectively. Two weeks after withdrawal of administration, although the expression ratio of γH2AX was markedly reduced in all groups, it remained high in BBN (17±1.9) and 2-NA (19±3.4) groups compared with the controls (0.6±0.9). Discussion and conclusion: BBN and 2-NA, genotoxic bladder carcinogens, induced more extensive γH2AX expression in the urothelium than other non-genotoxic (melamine and uracil) or non-carcinogenic chemicals (BMP and PEITC), and γH2AX-positive cells remained in relatively large numbers even 2 weeks after withdrawal of its administration. In addition, ratio of basal cells, intermediate cells and umbrella cells in γH2AX-positive cells showed similar patterns in BBN/2-NA and melamine/uracil groups. These data indicate that γH2AX has potential as a biomarker for early detection of genotoxic carcinogen in the urinary bladder. Citation Format: Takeshi Toyoda, Young-Man Cho, Jun-ichi Akagi, Yasuko Mizuta, Kumiko Ogawa. Expression of γH2AX as a biomarker of genotoxic carcinogen in the urinary bladder of rats. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4580. doi:10.1158/1538-7445.AM2015-4580

Highlights from Recent Cancer Literature

Highlights from Recent Cancer Literature

A computational method for the identification of new candidate carcinogenic and non-carcinogenic chemicals.

Cancer is one of the leading causes of human death. Based on current knowledge, one of the causes of cancer is exposure to toxic chemical compounds, including radioactive compounds, dioxin, and arsenic. The identification of new carcinogenic chemicals may warn us of potential danger and help to identify new ways to prevent cancer. In this study, a computational method was proposed to identify potential carcinogenic chemicals, as well as non-carcinogenic chemicals. According to the current validated carcinogenic and non-carcinogenic chemicals from the CPDB (Carcinogenic Potency Database), the candidate chemicals were searched in a weighted chemical network constructed according to chemical-chemical interactions. Then, the obtained candidate chemicals were further selected by a randomization test and information on chemical interactions and structures. The analyses identified several candidate carcinogenic chemicals, while those candidates identified as non-carcinogenic were supported by a literature search. In addition, several candidate carcinogenic/non-carcinogenic chemicals exhibit structural dissimilarity with validated carcinogenic/non-carcinogenic chemicals.

Comparison of Cramer classification between Toxtree, the OECD QSAR Toolbox and expert judgment

The Threshold of Toxicological Concern (TTC) is a pragmatic approach in risk assessment. In the absence of data, it sets up levels of human exposure that are considered to have no appreciable risk to human health. The Cramer decision tree is used extensively to determine these exposure thresholds by categorizing non-carcinogenic chemicals into three different structural classes. Therefore, assigning an accurate Cramer class to a material is a crucial step to preserve the integrity of the risk assessment. In this study the Cramer class of over 1000 fragrance materials across diverse chemical classes were determined by using Toxtree (TT), the OECD QSAR Toolbox (TB), and expert judgment. Disconcordance was observed between TT and the TB. A total of 165 materials (16%) showed different results from the two programs. The overall concordance for Cramer classification between TT and expert judgment is 83%, while the concordance between the TB and expert judgment is 77%. Amines, lactones and heterocycles have the lowest percent agreement with expert judgment for TT and the TB. For amines, the expert judgment agreement is 45% for TT and 55% for the TB. For heterocycles, the expert judgment agreement is 55% for TT and the TB. For lactones, the expert judgment agreement is 56% for TT and 50% for the TB. Additional analyses were conducted to determine the concordance within various chemical classes. Critical checkpoints in the decision tree are identified. Strategies and guidance on determining the Cramer class for various chemical classes are discussed.

Artificial Analogs of Naturally Occurring Tumor Promoters as Biochemical Tools and Therapeutic Leads

Tumor promoters are non-carcinogenic chemicals that enhance tumor formation when administered repeatedly after a low dose of a carcinogen. Phorbol esters, teleocidins, and aplysiatoxins are typical examples of naturally occurring tumor promoters. All of them share the ability to bind and activate protein kinase C (PKC) despite the differences in their chemical structures. A variety of analogs with unique chemical and biological properties have been developed to analyze the molecular mechanism of tumor promotion through PKC activation. Moreover, coupled with the emerging significance of PKC in the pathological processes of Alzheimer's disease (AD) and acquired immune deficiency syndrome (AIDS) as well as cancer, several efforts have been made recently to generate analogs of tumor promoters with therapeutic potential. This review focuses on artificial analogs of phorbol esters, teleocidins, and aplysiatoxins, and discusses their potential as biochemical tools and therapeutic leads.

Risk characterization for toxic chemicals transported in aquifers

The risk characterization resulting from the introduction of toxic chemicals in a subsurface flow field is presented. The concept of concentration threshold is used to quantify the risk associated with non-carcinogenic chemicals introduced to the population by ingestion of groundwater as the exposure pathway. The risk assessment methodology presented uses the expected mass fraction (EMF) concept with exposure duration to identify the distribution of dosage over different concentrations during the plume migration over the well location. The numerical simulation of the subsurface transport by advection and local diffusion is used to produce the concentration plume that passes different locations of interest. The EMF obtained presents the probability of the expected mass above some concentration threshold found at the location of interest. The risk formulation is defined with the risk reliability (safety) and its complement, the risk exceedance (failure) value. The risk characterization is obtained as a probability for exceeding the human reference dose which is considered uncertain due to the necessary extrapolation between concentration used in toxicological studies and the concentration to which humans could be exposed in nature. The final risk assessment expression is derived in a closed form by coupling the expected mass fraction with the safe human threshold concentration probability density function (pdf) inferred from the toxicological studies. The results indicate the importance of estimating the probability of a concentration mass found at locations of interest together with its exposure duration. The exposure duration was revealed to be an important parameter that needs to be estimated depending on the human concentration threshold selected and the distance from the source. The results in terms of the risk safety and risk failure also indicate the dilution effect on the passing concentration plume in the subsurface as a function of the distance and orientation from the source. Inclusion of uncertainty in the selection of the human concentration threshold shows the important effect on the risk quantification.

The Role of MicroRNA in Chemical Carcinogenesis

MicroRNAs (miRNAs) are important regulators of gene expression. Alteration of miRNA expression caused by exposure of different carcinogens has been well reported. This review aims to present the miRNAs dysregulated by exposure of different types of carcinogens in different biological systems and to discuss their potential roles in different stages of chemical carcinogenesis, following an introduction of miRNA biogenesis, regulatory mechanisms, and target identification. Available information shows that expression of a large number of miRNAs is readily changed by exposure of carcinogens in tissue- and chemical-specific manners. Carcinogenic agents generally induce many more changes in miRNA expression than non-carcinogenic chemicals. There are many more changes in cancer-target tissues than in the non-target tissues after acute or chronic exposure to carcinogens. Many of the miRNAs deregulated by carcinogens are involved in regulation of genes that are important for every stage of chemical carcinogenesis, including xenobiotic metabolism, carcinogen-induced hypomethylation, DNA repair, apoptosis, cell proliferation, tumor suppression, cell transformation, oncogenesis, tumor angiogenesis, tumor progress, mangliant transformation, and other functions. Many miRNAs function as putative oncogenes and tumor suppressor genes. The carcinogenic functions of carcinogens may be dependent on the balance between tumor-suppressor miRNAs and oncogenic miRNAs. Thus, the miRNA profiles and miRNAs specific to carcinogen exposure have the potential to be used as biomarkers for identifying genotoxicity and carcinogenicity of chemicals and indicating exposure of carcinogens.

TOX 21: New Dimensions of Toxicity Testing

On the ground floor of the National Institutes of Health Chemical Genomics Center (NCGC) in Rockville, Maryland, a $10-million automated laboratory spends all day and night screening chemicals at speeds no team of human researchers could ever match. In a week, depending on the nature of the assay, it can yield up to 2.2 million molecular data points derived from thousands of chemicals tested at 15 concentrations each.