Regulation of priority carcinogens and reproductive or developmental toxicants.

PubMed

Hooper, K; LaDou, J; Rosenbaum, J S; Book, S A

1992-01-01

In California, 370 carcinogens and 112 reproductive/developmental toxicants have been identified as a result of the State's Safe Drinking Water and Toxic Enforcement Act of 1986. They include pesticides, solvents, metals, industrial intermediates, environmental mixtures, and reactive agents. Occupational, environmental, and consumer product exposures that involve these agents are regulated under the Act. At levels of concern, businesses must provide warnings for and limit discharges of those chemicals. The lists of chemicals were compiled following systematic review of published data, including technical reports from the U.S. Public Health Service--National Toxicology Program (NTP), and evaluation of recommendations from authoritative bodies such as the International Agency for Research on Cancer (IARC) and the U.S. Environmental Protection Agency (USEPA). Given the large number of chemicals that are carcinogens or reproductive/developmental toxicants, regulatory concerns should focus on those that have high potential for human exposure, e.g., widely distributed or easily absorbed solvents, metals, environmental mixtures, or reactive agents. In this paper, we present a list of 33 potential priority carcinogens and reproductive/developmental toxicants, including alcoholic beverages, asbestos, benzene, chlorinated solvents, formaldehyde, glycol ethers, lead, tobacco smoke, and toluene.

Influence of Selected Organic Micropollutants on Organisms

NASA Astrophysics Data System (ADS)

Włodarczyk-Makuła, Maria

2017-03-01

This article describes the toxicity of organic micropollutants on tested microorganisms. Itis a current issue because organic micropollutants are identified in all elements of environmental (surface water, ground water, soils) and in food products. The organic micropollutants include: polychlorinated dibenzodioxyns PCDD, polychlorinated dibenzofurans PCDF, polychlorinated biphenyls PCB, polycyclic aromatic hydrocarbons PAH, halogenated compounds and by-products of water treatment. Some organic compounds cause hazard for health and human life due to their estrogenic biological activity, carcinogenic, mutagenic or teratogenic activity. The influence on organisms indicators of these compounds based on literature data were presented. The level of TEQ (toxic equivalency) in response to organic chlorine derivatives (PCDDs, PCDF, PCBs) is usually determined by toxic equivalency factor (TEF). The International Agency for Research on Cancer classifies organic micropollutants as carcinogenic to humans (Group 1), possibly carcinogenic (Group 2A) or probably carcinogenic to humans (Group 2B).

Issues in the Design and Interpretation of Chronic Toxicity and Carcinogenicity Studies in Rodents: Approaches to Dose Selection

EPA Science Inventory

For more than three decades chronic studies in rodents have been the benchmark for assessing the potential long-term toxicity, and particularly the carcinogenicity, of chemicals. With doses typically administered for about 2 years (18 months to lifetime), the rodent bioassay has ...

CEBS: a comprehensive annotated database of toxicological data

PubMed Central

Lea, Isabel A.; Gong, Hui; Paleja, Anand; Rashid, Asif; Fostel, Jennifer

2017-01-01

The Chemical Effects in Biological Systems database (CEBS) is a comprehensive and unique toxicology resource that compiles individual and summary animal data from the National Toxicology Program (NTP) testing program and other depositors into a single electronic repository. CEBS has undergone significant updates in recent years and currently contains over 11 000 test articles (exposure agents) and over 8000 studies including all available NTP carcinogenicity, short-term toxicity and genetic toxicity studies. Study data provided to CEBS are manually curated, accessioned and subject to quality assurance review prior to release to ensure high quality. The CEBS database has two main components: data collection and data delivery. To accommodate the breadth of data produced by NTP, the CEBS data collection component is an integrated relational design that allows the flexibility to capture any type of electronic data (to date). The data delivery component of the database comprises a series of dedicated user interface tables containing pre-processed data that support each component of the user interface. The user interface has been updated to include a series of nine Guided Search tools that allow access to NTP summary and conclusion data and larger non-NTP datasets. The CEBS database can be accessed online at http://www.niehs.nih.gov/research/resources/databases/cebs/. PMID:27899660

IRIS TOXICOLOGICAL REVIEW AND SUMMARY ...

EPA Pesticide Factsheets

EPA's assessment of the noncancer health effects and carcinogenic potential of 1,2,3-trichloropropane (TCP) was added to the IRIS database in 1990. The IRIS program is updating the IRIS assessment for TCP. This update will incorporate health effects information published since the last assessment was prepared as well as new risk assessment methods. The IRIS assessment for TCP will consist of a Toxicological Review and IRIS Summary. The Toxicological Review is a critical review of the physicochemical and toxicokinetic properties of the chemical and its toxicity in humans and experimental systems. The assessment will present reference values for noncancer effects of TCP (RfD and RfC) and a cancer assessment. The Toxicological Review and IRIS Summary will be subject to internal peer consultation, Agency review, and external scientific peer review. The final products will constitute the Agency's opinion on the toxicity of TCP. EPA is undertaking an Integrated Risk Information System (IRIS) health assessment for 1,2,3-trichloropropane. IRIS is an EPA database containing the Agency's consensus scientific positions on potential adverse human effects that may result from chronic (or lifetime) exposure to chemicals in the environment. IRIS contains chemical-specific summaries of qualitative and quantitative health information in support of two steps of the risk assessment process, i.e., hazard identification and dose-response evaluation. IRIS assessments are used in

Identifying occupational carcinogens: an update from the IARC Monographs.

PubMed

Loomis, Dana; Guha, Neela; Hall, Amy L; Straif, Kurt

2018-05-16

The recognition of occupational carcinogens is important for primary prevention, compensation and surveillance of exposed workers, as well as identifying causes of cancer in the general population. This study updates previously published lists of known occupational carcinogens while providing additional information on cancer type, exposure scenarios and routes, and discussing trends in the identification of carcinogens over time. Data were extracted from International Agency for Research on Cancer (IARC) Monographs covering the years 1971-2017, using specific criteria to ensure occupational relevance and provide high confidence in the causality of observed exposure-disease associations. Selected agents were substances, mixtures or types of radiation classified in IARC Group 1 with 'sufficient evidence of carcinogenicity' in humans from studies of exposed workers and evidence of occupational exposure documented in the pertinent monograph. The number of known occupational carcinogens has increased over time: 47 agents were identified as known occupational carcinogens in 2017 compared with 28 in 2004. These estimates are conservative and likely underestimate the number of carcinogenic agents present in workplaces. Exposure to these agents causes a wide range of cancers; cancers of the lung and other respiratory sites, followed by skin, account for the largest proportion. The dominant routes of exposure are inhalation and dermal contact. Important progress has been made in identifying occupational carcinogens; nevertheless, there is an ongoing need for research on the causes of work-related cancer. Most workplace exposures have not been evaluated for their carcinogenic potential due to inadequate epidemiologic evidence and a paucity of quantitative exposure data. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

BENZENE OXIDE PROTEIN ADDUCTS AS BIOMARKERS OF BENZENE EXPOSURE

EPA Science Inventory

Benzene is known to be hematotoxic and carcinogenic in animals and humans. While metabolism is required for toxicity, the identity of the ultimate carcinogen(s) remains unknown. Benzene oxide (BO) is the first and most abundant of the metabolites, but very little is known about...

Development of Quantitative Structure-Activity Relationship (QSAR) Models to Predict the Carcinogenic Potency of Chemicals

EPA Science Inventory

Determining the carcinogenicity and carcinogenic potency of new chemicals is both a labor-intensive and time-consuming process. In order to expedite the screening process, there is a need to either: (1) identify alternative toxicity measures (shorter duration) that may be used as...

Carcinogenic Effects of Benzene: An Update (Draft Report)

EPA Science Inventory

The major issue addressed in this document involves the nature and magnitude of the risk of cancer to humans exposed to low levels of benzene. Occupational studies continue to provide the bulk of evidence of benzenes carcinogenicity. Workers are exposed at much higher levels than...

Toxic substances handbook

NASA Technical Reports Server (NTRS)

Junod, T. L.

1979-01-01

Handbook, published in conjunction with Toxic Substances Alert Program at NASA Lewis Research Center, profiles 187 toxic chemicals in their relatively pure states and include 27 known or suspected carcinogens.

Aberrant activation of ubiquitin D at G2 phase and apoptosis by carcinogens that evoke cell proliferation after 28-day administration in rats.

PubMed

Taniai, Eriko; Yafune, Atsunori; Hayashi, Hitomi; Itahashi, Megu; Hara-Kudo, Yukiko; Suzuki, Kazuhiko; Mitsumori, Kunitoshi; Shibutani, Makoto

2012-01-01

We have previously reported that renal carcinogens examined in rats increase tubular cell proliferation and topoisomerase (Topo) IIα(+) cells. The present study was aimed at identifying early prediction markers of carcinogens after 28-day treatment in rats. Following gene expression screening by microarrays in renal tubules with renal carcinogens, immunohistochemical analysis and TUNEL-assay were performed with carcinogens targeting different organs. All renal carcinogens tested (ferric nitrilotriacetic acid, ochratoxin A (OTA), monuron, tris(2-chloroethyl) phosphate, and potassium bromate) increased tubular cells immunoreactive for minichromosome maintenance 3 (Mcm3) or ubiquitin D (Ubd) or those showing apoptosis, compared with untreated controls or non-carcinogenic renal toxicants. Carcinogens targeting the liver (thioacetamide (TAA), fenbendazole, piperonyl butoxide (PBO) and methyleugenol), thyroid (sulfadimethoxine), urinary bladder (phenylethyl isothiocyanate), forestomach (butylated hydroxyanisole), glandular stomach (catechol), and colon (chenodeoxycholic acid and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) were examined for induction of Mcm3, Ubd, Topo IIα, Ki-67 and apoptosis using non-carcinogenic toxicants as negative controls. All carcinogens increased Mcm3(+), Ubd(+), Topo IIα(+), Ki-67(+) or TUNEL(+) cells, except for hepatocarcinogen PBO and both colon carcinogens, which did not increase cell proliferation. Ubd(+) cells co-expressing Topo IIα was increased without changing phospho-Histone H3-co-expressing cell population as examined with OTA and TAA. Results revealed cooperative responses of Topo IIα, Ubd and apoptosis by carcinogens inducing high proliferation activity, irrespective of target organs, examined here after a 28-day administration. Aberrant expression of Ubd at G(2) phase and increased apoptosis reflecting aberrant cell cycle regulation may be the common feature of these carcinogens.

Recommended health and safety guidelines for coal gasification pilot plants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1978-01-01

The greatest toxic hazards in coal conversion are presented by the known and suspected carcinogens, because they are hazardous at low levels of exposure, have delayed action with no immediate warning, and have grave consequences. As for routes of entry, it is to be noted that various solids and liquids may reach the body by inhalation of particles, deposition of particles, or indirectly by contact with dirty surfaces. Other toxicants are most likely to enter the body by inhalation. The overall carcinogenic hazard cannot be precisely estimated from chemical analysis alone, because the possible interactions are far too complex. Further,more » the hazard cannot at present be quantitatively defined by available biological tests. The same limitations probably apply to toxic effects other than carcinogenesis, with the posible exception of some immediate responses (e.g., chemical asphyxia, primary respiratory irration). It is not practical to recommend comprehensive workplace exposure limits on a basis similar to those for individual toxicants; however, a limit for one important kind of hazard (high-boiling suspected carcinogens) can be recommended. The carcinogenic hazards associated with airborne particles and surface contamination are the most crucial of the whole spectrum and offer a practical target for control, if not for quantitative evaluation. The only direct quantitative evidence now availabl is from epidemiology in analogous circulstances and there are severe limitations on the comprehensiveness and reliability of such evidence. Some specific targets for control through industrial hygiene practices can be identified. The presence of any strong irritant of the respiratory mucosa, other mucous surfaces, and the skin should be regarded as a danger signal because of possible potentiation of carcinogens and other toxicants.« less

Carcinogenic Air Toxics Exposure and Their Cancer-Related Health Impacts in the United States.

PubMed

Zhou, Ying; Li, Chaoyang; Huijbregts, Mark A J; Mumtaz, M Moiz

2015-01-01

Public health protection from air pollution can be achieved more effectively by shifting from a single-pollutant approach to a multi-pollutant approach. To develop such multi-pollutant approaches, identifying which air pollutants are present most frequently is essential. This study aims to determine the frequently found carcinogenic air toxics or hazardous air pollutants (HAPs) combinations across the United States as well as to analyze the health impacts of developing cancer due to exposure to these HAPs. To identify the most commonly found carcinogenic air toxics combinations, we first identified HAPs with cancer risk greater than one in a million in more than 5% of the census tracts across the United States, based on the National-Scale Air Toxics Assessment (NATA) by the U.S. EPA for year 2005. We then calculated the frequencies of their two-component (binary), and three-component (ternary) combinations. To quantify the cancer-related health impacts, we focused on the 10 most frequently found HAPs with national average cancer risk greater than one in a million. Their cancer-related health impacts were calculated by converting lifetime cancer risk reported in NATA 2005 to years of healthy life lost or Disability-Adjusted Life Years (DALYs). We found that the most frequently found air toxics with cancer risk greater than one in a million are formaldehyde, carbon tetrachloride, acetaldehyde, and benzene. The most frequently occurring binary pairs and ternary mixtures are the various combinations of these four air toxics. Analysis of urban and rural HAPs did not reveal significant differences in the top combinations of these chemicals. The cumulative annual cancer-related health impacts of inhaling the top 10 carcinogenic air toxics included was about 1,600 DALYs in the United States or 0.6 DALYs per 100,000 people. Formaldehyde and benzene together contribute nearly 60 percent of the total cancer-related health impacts. Our study shows that although there are many carcinogenic air toxics, only a few of them affect public health significantly at the national level in the United States, based on the frequency of occurrence of air toxics mixtures and cancer-related public health impacts. Future research is needed on their joint toxicity and cumulative health impacts.

TRANSCRIPTOMIC ANALYSIS OF F344 RAT NASAL EPITHELIUM SUGGESTS THAT THE LACK OF CARCINOGENIC RESPONSE TO GLUTARALDEHYDE IS DUE TO ITS GREATER TOXICITY COMPARED TO FORMALDEHYDE

EPA Science Inventory

Formaldehyde is cytotoxic and carcinogenic to the rat nasal respiratory epithelium inducing tumors after 12 months. Glutaraldehyde is also cytotoxic but is not carcinogenic to nasal epithelium even after 24 months. Both aldehydes induce similar acute and subchronic histopathology...

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

PubMed

Chen, Lei; Chu, Chen; Lu, Jing; Kong, Xiangyin; Huang, Tao; Cai, Yu-Dong

2015-09-01

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.

IRIS Toxicological Review and Summary Documents for N ...

EPA Pesticide Factsheets

EPA's assessment of the noncancer health effects and carcinogenic potential of n-hexane was last prepared and added to the IRIS data base in 1990. The IRIS program is updating the IRIS assessment for n-hexane; this update will incorporate health effects information published since the last assessment was prepared as well as new risk assessment methods. The IRIS assessment for n-hexane will consist of a Toxicological Review and IRIS Summary. The Toxicological Review is a critical review of the physicochemical and toxicokinetic properties of the chemical and its toxicity in humans and experimental systems. The assessment will present reference values for noncancer effects of n-hexane (RfD and RfC) and a cancer assessment, where supported by available data. The Toxicological Review and IRIS Summary will be subject to internal peer consultation, Agency review, and external scientific peer review. EPA is undertaking an update of the Integrated Risk Information System (IRIS) health assessment for n-hexane. The outcome of this project is an updated Toxicological Review and IRIS Summary for n-Hexane that will be entered into the IRIS database. IRIS is an EPA data base containing Agency scientific positions on potential adverse human health effects that may result from chronic (or lifetime) exposure to chemicals in the environment. IRIS contains chemical-specific summaries of qualitative and quantitative health information in support of two steps of the risk assessment

Toxicity prediction of compounds from turmeric (Curcuma longa L).

PubMed

Balaji, S; Chempakam, B

2010-10-01

Turmeric belongs to the ginger family Zingiberaceae. Currently, cheminformatics approaches are not employed in any of the spices to study the medicinal properties traditionally attributed to them. The aim of this study is to find the most efficacious molecule which does not have any toxic effects. In the present study, toxicity of 200 chemical compounds from turmeric were predicted (includes bacterial mutagenicity, rodent carcinogenicity and human hepatotoxicity). The study shows out of 200 compounds, 184 compounds were predicted as toxigenic, 136 compounds are mutagenic, 153 compounds are carcinogenic and 64 compounds are hepatotoxic. To cross validate our results, we have chosen the popular curcumin and found that curcumin and its derivatives may cause dose dependent hepatotoxicity. The results of these studies indicate that, in contrast to curcumin, few other compounds in turmeric which are non-mutagenic, non-carcinogenic, non-hepatotoxic, and do not have any side-effects. Hence, the cost-effective approach presented in this paper could be used to filter toxic compounds from the drug discovery lifecycle. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

IRIS TOXICOLOGICAL REVIEW AND SUMMARY DOCUMENTS FOR BERYLLIUM AND COMPOUNDS

EPA Science Inventory

EPA's assessment of the noncancer health effects and carcinogenic potential of Beryllium was added to the IRIS database in 1998. The IRIS program is updating the IRIS assessment for Beryllium. This update will incorporate health effects information published since the last assess...

Nitrosamine toxicity and metabolism. May 1978-October 1989 (A Bibliography from the Life Sciences Collection data base). Report for May 1978-October 1989

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

This bibliography contains citations concerning the toxicity, metabolism, and carcinogenicity of nitrosamines. Nitrosamines occur in foods, tobacco products, industrial emissions, cosmetics, beverages, and rubber products. Articles include testing methods for nitrosamine carcinogenicity and mutagenicity, analysis and determination in various food and cosmetic products, relative toxicities of nitrosamines, metabolism of nitrosamines, and their production in foods and the human intestinal system. Animal studies of nitrosamine toxicology are not included in this publication. Nitrosamine contents of meat products are referenced in a related published bibliography. (Contains 176 citations fully indexed and including a title list.)

E-cigarette puffing patterns associated with high and low nicotine e-liquid strength: effects on toxicant and carcinogen exposure.

PubMed

Cox, Sharon; Kośmider, Leon; McRobbie, Hayden; Goniewicz, Maciej; Kimber, Catherine; Doig, Mira; Dawkins, Lynne

2016-09-20

Contrary to intuition, use of lower strength nicotine e-liquids might not offer reduced health risk if compensatory puffing behaviour occurs. Compensatory puffing (e.g. more frequent, longer puffs) or user behaviour (increasing the wattage) can lead to higher temperatures at which glycerine and propylene glycol (solvents used in e-liquids) undergo decomposition to carbonyl compounds, including the carcinogens formaldehyde and acetaldehyde. This study aims to document puffing patterns and user behaviour associated with using high and low strength nicotine e-liquid and associated toxicant/carcinogen exposure in experienced e-cigarette users (known as vapers herein). A counterbalanced repeated measures design. Non-tobacco smoking vapers; have used an e-cigarette for ≥3 months; currently using nicotine strength e-liquid ≥12mg/mL and a second or third generation device. This study will measure puffing patterns in vapers whilst they use high and low strength nicotine e-liquid under fixed and user-defined settings, each for a week. The 4 counterbalanced conditions are: i) low strength (6mg/mL), fixed settings; ii) low strength user-defined settings; iii) high strength (18mg/mL) fixed settings; iv) high strength user-defined settings. Biomarkers of exposure to toxicants and carcinogens will be measured in urine. In the second phase of this study, toxicant yields will be measured in aerosol generated using a smoking machine operated to replicate the puffing behaviours of each participant. i) Puffing patterns (mean puff number, puff duration, inter-puff interval and mL of liquid consumed) and user behaviour (changes to device settings: voltage and air-flow) associated with using high and low strength nicotine e-liquid. ii) Toxicant/carcinogen exposure associated with the puffing patterns/device settings used by our participants. i) Subjective effects. ii) comparisons with toxicant exposure from tobacco smoke (using documented evidence) and with recommended safety limits. Twenty participants. The findings will have important implications for public health messaging regarding the relative risks and subjective effects associated with using high and low strength nicotine e-liquid, and for policy makers regarding regulations on nicotine concentrations in e-liquids.

Investigating the Mechanisms of Action and the Identification of Breast Carcinogens by Computational Analysis of Female Rodent Carcinogens

DTIC Science & Technology

2005-08-01

QSAR in Environmental Researth was accepted and published in April of 2005. The manuscript described the cat -SAR program in detail. We note the...analysis of this data yielded a very good model. As such, this was a suitable dataset on which to develop and test the cat -SAR program. A copy of the...developed and validated (i.e., a-c) as planned in MCASE and then with the cat -SAR program. We have also updated rodent carcinogenicity models so that

IRIS TOXICOLOGICAL REVIEW AND SUMMARY DOCUMENTS FOR 1,2,3-TRICHLOROPROPANE

EPA Science Inventory

EPA's assessment of the noncancer health effects and carcinogenic potential of 1,2,3-trichloropropane (TCP) was added to the IRIS database in 1990. The IRIS program is updating the IRIS assessment for TCP. This update will incorporate health effects information published since t...

Carcinogenicity of chromium and chemoprevention: a brief update

PubMed Central

Gu, Yuanliang; Song, Xin; Zhao, Jinshun

2017-01-01

Chromium has two main valence states: hexavalent chromium (Cr[VI]) and trivalent chromium (Cr[III]). Cr(VI), a well-established human carcinogen, can enter cells by way of a sulfate/phosphate anion-transport system, and then be reduced to lower-valence intermediates consisting of pentavalent chromium (Cr[V]), tetravalent chromium (Cr[IV]) or Cr(III) via cellular reductants. These intermediates may directly or indirectly result in DNA damage or DNA–protein cross-links. Although Cr(III) complexes cannot pass easily through cell membranes, they have the ability to accumulate around cells to induce cell-surface morphological alteration and result in cell-membrane lipid injuries via disruption of cellular functions and integrity, and finally to cause DNA damage. In recent years, more research, including in vitro, in vivo, and epidemiological studies, has been conducted to evaluate the genotoxicity/carcinogenicity induced by Cr(VI) and/or Cr(III) compounds. At the same time, various therapeutic agents, especially antioxidants, have been explored through in vitro and in vivo studies for preventing chromium-induced genotoxicity/carcinogenesis. This review aims to provide a brief update on the carcinogenicity of Cr(VI) and Cr(III) and chemoprevention with different antioxidants. PMID:28860815

NANOSTRUCTURED POROUS SILICON AND LUMINESCENT POLYSILOLES AS CHEMICAL SENSORS FOR CARCINOGENIC CHROMIUM(VI) AND ARSENIC(V)

EPA Science Inventory

The chief goal is to develop new selective solid state sensors for carcinogenic and toxic chromium(VI) and arsenic(V) in water based on redox quenching of the luminescence from nanostructured porous silicon and polysiloles.

Principles and Procedures for Evaluating the Toxicity of Household Substances. Revised.

ERIC Educational Resources Information Center

National Academy of Sciences - National Research Council, Washington, DC. Assembly of Life Sciences.

This report was prepared for use by the professional toxicologist. It contains chapters on ingestion exposure, dermal and dye toxicity tests, inhalation exposure, chronic toxicity and carcinogenicity tests, mutagenicity tests, reproduction and teratogenicity tests, and behavioral toxicity tests. In addition, regulations under the Federal Hazardous…

Human health effects of dichloromethane: key findings and scientific issues.

PubMed

Schlosser, Paul M; Bale, Ambuja S; Gibbons, Catherine F; Wilkins, Amina; Cooper, Glinda S

2015-02-01

The U.S. EPA's Integrated Risk Information System (IRIS) completed an updated toxicological review of dichloromethane in November 2011. In this commentary we summarize key results and issues of this review, including exposure sources, identification of potential health effects, and updated physiologically based pharmacokinetic (PBPK) modeling. We performed a comprehensive review of primary research studies and evaluation of PBPK models. Hepatotoxicity was observed in oral and inhalation exposure studies in several studies in animals; neurological effects were also identified as a potential area of concern. Dichloromethane was classified as likely to be carcinogenic in humans based primarily on evidence of carcinogenicity at two sites (liver and lung) in male and female B6C3F1 mice (inhalation exposure) and at one site (liver) in male B6C3F1 mice (drinking-water exposure). Recent epidemiologic studies of dichloromethane (seven studies of hematopoietic cancers published since 2000) provide additional data raising concerns about associations with non-Hodgkin lymphoma and multiple myeloma. Although there are gaps in the database for dichloromethane genotoxicity (i.e., DNA adduct formation and gene mutations in target tissues in vivo), the positive DNA damage assays correlated with tissue and/or species availability of functional glutathione S-transferase (GST) metabolic activity, the key activation pathway for dichloromethane-induced cancer. Innovations in the IRIS assessment include estimation of cancer risk specifically for a presumed sensitive genotype (GST-theta-1+/+), and PBPK modeling accounting for human physiological distributions based on the expected distribution for all individuals 6 months to 80 years of age. The 2011 IRIS assessment of dichloromethane provides insights into the toxicity of a commonly used solvent.

Toxicity and Carcinogenicity Studies of Ginkgo biloba extract in Rat and Mouse: Liver, Thyroid, and Nose are Targets

PubMed Central

Rider, Cynthia V.; Nyska, Abraham; Cora, Michelle C.; Kissling, Grace E.; Smith, Cynthia; Travlos, Gregory S.; Hejtmancik, Milton R.; Fomby, Laurene M.; Colleton, Curtis A.; Ryan, Michael J.; Kooistra, Linda; Morrison, James P.; Chan, Po C.

2014-01-01

Ginkgo biloba extract (GBE) is a popular herbal supplement that is used to improve circulation and brain function. In spite of widespread human exposure to relatively high doses over potentially long periods of time, there is a paucity of data from animal studies regarding the toxicity and carcinogenicity associated with GBE. In order to fill this knowledge gap, three-month and two-year toxicity and carcinogenicity studies with GBE administered by oral gavage to B6C3F1/N mice and F344/N rats were performed as part of the National Toxicology Program’s Dietary Supplements and Herbal Medicines Initiative. The targets of GBE treatment were the liver, thyroid, and nose. These targets were consistent across exposure period, sex, and species, albeit with varying degrees of effect observed among studies. Key findings included a notably high incidence of hepatoblastomas in male and female mice and evidence of carcinogenic potential in the thyroid gland of both mice and rats. Various nonneoplastic lesions were observed beyond control levels in the liver, thyroid gland, and nose of rats and mice administered GBE. Although these results cannot be directly extrapolated to humans, the findings fill an important data gap in assessing risk associated with GBE use. PMID:23960164

Selenium: Poison and Preventive.

ERIC Educational Resources Information Center

Marmion Howe, Sister

1978-01-01

Selenium is an essential nutrient to the human body, but it can reach toxic levels causing a disease called selenosis. This article discusses selenium, its geographical distribution, toxicity, nutritional role, and carcinogenicity. (MA)

A novel approach: chemical relational databases, and the role of the ISSCAN database on assessing chemical carcinogenicity.

PubMed

Benigni, Romualdo; Bossa, Cecilia; Richard, Ann M; Yang, Chihae

2008-01-01

Mutagenicity and carcinogenicity databases are crucial resources for toxicologists and regulators involved in chemicals risk assessment. Until recently, existing public toxicity databases have been constructed primarily as "look-up-tables" of existing data, and most often did not contain chemical structures. Concepts and technologies originated from the structure-activity relationships science have provided powerful tools to create new types of databases, where the effective linkage of chemical toxicity with chemical structure can facilitate and greatly enhance data gathering and hypothesis generation, by permitting: a) exploration across both chemical and biological domains; and b) structure-searchability through the data. This paper reviews the main public databases, together with the progress in the field of chemical relational databases, and presents the ISSCAN database on experimental chemical carcinogens.

Perinatal Toxicity and Carcinogenicity Studies of Styrene –Acrylonitrile Trimer, A Ground Water Contaminant

PubMed Central

Behl, Mamta; Elmore, Susan A.; Malarkey, David E.; Hejtmancik, Milton R.; Gerken, Diane K.; Chhabra, Rajendra S.

2015-01-01

Styrene Acrylonitrile (SAN) Trimer is a by-product in the production of acrylonitrile styrene plastics. Following a report of a childhood cancer cluster in the Toms River section of Dover Township, New Jersey, SAN Trimer was identified as one of the groundwater contaminants at Reich Farm Superfund site in the township. The contaminants from the Reich Farm site’s ground water plume impacted two wells at the Parkway well field. The National Toxicology Program (NTP) studied the toxicity and carcinogenicity of SAN Trimer in rats exposed during their perinatal developmental period and adulthood. The chronic toxicity and carcinogenicity studies in F344/N rats were preceded by 7- and 18-week perinatal toxicity studies to determine the exposure concentrations for the 2-year studies. Subsequently, Fisher 344 pregnant dams were exposed to SAN Trimer containing diet at 400, 800, or 1600 ppm concentrations during gestation, nursing and weaning periods of offspring followed by two year of adult exposures to both male and female pups. There was no statistically significant evidence of carcinogenic activity following SAN-Trimer exposure; however, rare neoplasms in the brain and spinal cord were observed in males and to lesser extent in female rats. These incidences were considered within the range of historical background in the animal model used in the current studies. Therefore, the presence of a few rarely occurring CNS tumors in the treated groups were not judged to be associated with the SAN Trimer exposure. The major finding was a dose-related peripheral neuropathy associated with the sciatic nerves in females and spinal nerve roots in males and females thereby suggesting that SAN trimer is potentially a nervous system toxicant. PMID:24060431

Molecular and cellular mechanisms of hexavalent chromium-induced lung cancer: an updated perspective.

PubMed

Urbano, A M; Ferreira, L M R; Alpoim, M C

2012-03-01

For over a century, chromium (Cr) has found widespread industrial and commercial use, namely as a pigment, in the production of stainless steel and in chrome plating. The adverse health effects to the skin and respiratory tract of prolonged exposure to Cr have been known or suspected for a long time, but it was much more recently that the toxicity of this element was unequivocally attributed to its hexavalent state. Based on the combined results of extensive epidemiological studies, animal carcinogenicity studies and several types of other relevant data, authoritative regulatory agencies have found sufficient evidence to classify hexavalent chromium [Cr(VI)] compounds as encountered in the chromate production, chromate pigment production and chromium plating industries as carcinogenic to humans. Crucial for the development of novel strategies to prevent, detect and/or treat Cr(VI)-induced cancers is a detailed knowledge of the molecular and cellular mechanisms underlying these pathologies. Unfortunately, in spite of a considerable research effort, crucial facets of these mechanisms remain essentially unknown. This review is intended to provide a concise, integrated and critical perspective of the current state of knowledge concerning multiple aspects of Cr(VI) carcinogenesis. It will present recent theories of Cr(VI)-induced carcinogenesis and will include aspects not traditionally covered in other reviews, such as the possible involvement of the energy metabolism in this process. A brief discussion on the models that have been used in the studies of Cr(VI)-induced carcinogenicity will also be included, due to the impact of this parameter on the relevance of the results obtained.

Trichloroethylene: Mechanistic, epidemiologic and other supporting evidence of carcinogenic hazard.

PubMed

Rusyn, Ivan; Chiu, Weihsueh A; Lash, Lawrence H; Kromhout, Hans; Hansen, Johnni; Guyton, Kathryn Z

2014-01-01

The chlorinated solvent trichloroethylene (TCE) is a ubiquitous environmental pollutant. The carcinogenic hazard of TCE was the subject of a 2012 evaluation by a Working Group of the International Agency for Research on Cancer (IARC). Information on exposures, relevant data from epidemiologic studies, bioassays in experimental animals, and toxicity and mechanism of action studies was used to conclude that TCE is carcinogenic to humans (Group 1). This article summarizes the key evidence forming the scientific bases for the IARC classification. Exposure to TCE from environmental sources (including hazardous waste sites and contaminated water) is common throughout the world. While workplace use of TCE has been declining, occupational exposures remain of concern, especially in developing countries. The strongest human evidence is from studies of occupational TCE exposure and kidney cancer. Positive, although less consistent, associations were reported for liver cancer and non-Hodgkin lymphoma. TCE is carcinogenic at multiple sites in multiple species and strains of experimental animals. The mechanistic evidence includes extensive data on the toxicokinetics and genotoxicity of TCE and its metabolites. Together, available evidence provided a cohesive database supporting the human cancer hazard of TCE, particularly in the kidney. For other target sites of carcinogenicity, mechanistic and other data were found to be more limited. Important sources of susceptibility to TCE toxicity and carcinogenicity were also reviewed by the Working Group. In all, consideration of the multiple evidence streams presented herein informed the IARC conclusions regarding the carcinogenicity of TCE. © 2013.

Trichloroethylene: Mechanistic, Epidemiologic and Other Supporting Evidence of Carcinogenic Hazard

PubMed Central

Rusyn, Ivan; Chiu, Weihsueh A.; Lash, Lawrence H.; Kromhout, Hans; Hansen, Johnni; Guyton, Kathryn Z.

2013-01-01

The chlorinated solvent trichloroethylene (TCE) is a ubiquitous environmental pollutant. The carcinogenic hazard of TCE was the subject of a 2012 evaluation by a Working Group of the International Agency for Research on Cancer (IARC). Information on exposures, relevant data from epidemiologic studies, bioassays in experimental animals, and toxicity and mechanism of action studies was used to conclude that TCE is carcinogenic to humans (Group 1). This article summarizes the key evidence forming the scientific bases for the IARC classification. Exposure to TCE from environmental sources (including from hazardous waste sites and contaminated water) is common throughout the world. While workplace use of TCE has been declining, occupational exposures remain of concern, especially in developing countries. Strongest human evidence is from studies of occupational TCE exposure and kidney cancer. Positive, although less consistent, associations were reported for liver cancer and non-Hodgkin's lymphoma. TCE is carcinogenic at multiple sites in multiple species and strains of experimental animals. The mechanistic evidence includes extensive data on the toxicokinetics and genotoxicity of TCE and its metabolites. Together, available evidence provided a cohesive database supporting the human cancer hazard of TCE, particularly in the kidney. For other target sites of carcinogenicity, mechanistic and other data were found to be more limited. Important sources of susceptibility to TCE toxicity and carcinogenicity were also reviewed by the Working Group. In all, consideration of the multiple evidence streams presented herein informed the IARC conclusions regarding the carcinogenicity of TCE. PMID:23973663

Application of Key Events and Analysis to Chemical Carcinogens and Noncarcinogens

EPA Science Inventory

The existence of thresholds for toxicants is a matter of debate in chemical rsk assessment and regulation. Current risk assessment methods are based on the assumption that, in the basense of sufficient data, carcinogenesis does not have a threshold, while non-carcinogenic endpoi...

A Novel Approach: Chemical Relational Databases, and the Role of the ISSCAN Database on Assessing Chemical Carcinogenity

EPA Science Inventory

Mutagenicity and carcinogenicity databases are crucial resources for toxicologists and regulators involved in chemicals risk assessment. Until recently, existing public toxicity databases have been constructed primarily as "look-up-tables" of existing data, and most often did no...

An Overview of the Toxicity of Naphthalene, EDB and Ethanol

EPA Science Inventory

This presentation is a short summary of information on the toxicity and carcinogenicity of naphthalene and 1,2-dibromoethane (EDB) that is available in the EPA Integrated Risk Information System (IRIS) and information on the toxicity of ethanol available from the Health, Environm...

Updated recommended lists of genotoxic and non-genotoxic chemicals for assessment of the performance of new or improved genotoxicity tests.

PubMed

Kirkland, David; Kasper, Peter; Martus, Hans-Jörg; Müller, Lutz; van Benthem, Jan; Madia, Federica; Corvi, Raffaella

2016-01-01

In 2008 we published recommendations on chemicals that would be appropriate to evaluate the sensitivity and specificity of new/modified mammalian cell genotoxicity tests, in particular to avoid misleading positive results. In light of new data it is appropriate to update these lists of chemicals. An expert panel was convened and has revised the recommended chemicals to fit the following different sets of characteristics: • Group 1: chemicals that should be detected as positive in in vitro mammalian cell genotoxicity tests. Chemicals in this group are all in vivo genotoxins at one or more endpoints, either due to DNA-reactive or non DNA-reactive mechanisms. Many are known carcinogens with a mutagenic mode of action, but a sub-class of probable aneugens has been introduced. • Group 2: chemicals that should give negative results in in vitro mammalian cell genotoxicity tests. Chemicals in this group are usually negative in vivo and non-DNA-reactive. They are either non-carcinogenic or rodent carcinogens with a non-mutagenic mode of action. • Group 3: chemicals that should give negative results in in vitro mammalian cell genotoxicity tests, but have been reported to induce gene mutations in mouse lymphoma cells, chromosomal aberrations or micronuclei, often at high concentrations or at high levels of cytotoxicity. Chemicals in this group are generally negative in vivo and negative in the Ames test. They are either non-carcinogenic or rodent carcinogens with an accepted non-mutagenic mode of action. This group contains comments as to any conditions that can be identified under which misleading positive results are likely to occur. This paper, therefore, updates these three recommended lists of chemicals and describes how these should be used for any test evaluation program. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Source identification, environmental risk assessment and human health risks associated with toxic elements present in a coastal industrial environment, India.

PubMed

Satapathy, Shreemayee; Panda, C R

2018-03-26

This study investigated the source and contamination levels of toxic elements (Cd, Cr, As, Pb, Ni and Hg) present in a coastal environment, Paradip-an industrial hub of the east coast of India. The ecological risk assessment indices and human exposure models were used to evaluate the pollution status. Enrichment factor indicated that all the metal(loid)s found in the sediment are mostly derived from the anthropogenic source. According to the sediment quality quotient, 8.33% of sediments have crossed the ERM limit for Ni that can be fatal to biota. Meanwhile, 66.66, 41.66 and 8.33% of sediments have exceeded PEL range for Cr, Ni and As, respectively, that can register frequent lethal toxicity to benthic biota. As had the highest potential ecological harm coefficient (Er f  > 80), and Hg had moderate ecological harm coefficient (40 < Er f  < 80). Summarily, the sediment quality of this site is moderate to heavily toxic to benthic organisms. The concentration of toxic metals in seawater was below the permissible limit (CCC and CMC) set by USEPA indicating that water is relatively safer for free floating aquatic biota. The health risk index of toxic metal (loid)s present in soils of the residential sites has confirmed that there is a severe non-carcinogenic threat for children (HI child > 1) and a borderline carcinogenic risk for both adult and children. THQ Cr possesses highest non-carcinogenic threat, which contributed approximately 50% to HI followed by THQ As . The contribution of carcinogenic risk of chromium (CR Cr ) to TCR is approximately 60%. Cr is the significant contaminant of this site that has highest health effects. Highest exposure risks were associated with ingestion pathway accounting for about 85% of the total for most of the elements.

PLATFORM SESSION "IMMUNOTOXICOLOGY", SOCIETY OF TOXICOLOGY 45TH ANNUAL MEETING, MARCH 5-9, 2006, SAN DIEGO, CA

EPA Science Inventory

For many years the primary endpoints for evaluating the toxicity of xenobiotics were carcinogenicity and mutagenicity. However, it gradually became apparent that exposure to chemicals at levels lower than those shown to be directly carcinogenic may negatively impact other facets...

[Hygienic assessment of carcinogenic and noncarcinogenic risks of oral intake of drinking water chemical agents].

PubMed

Ignat'eva, L P; Pogorelova, I G; Potapova, M O

2006-01-01

Based on the quantitative and qualitative determination of drinking water pollution by a large number of substances of varying toxicity and hazard, the authors calculated a possible risks of their adverse impact on the body by the development of carcinogenic and noncarcinogenic effects.

PERSONAL EXPOSURE TO FINE PARTICLE POLYCYCLIC AROMATIC HYDROCARBONS: OUTDOOR SOURCE TRACERS

EPA Science Inventory

The most carcinogenic and toxic polycyclic aromatic hydrocarbons (PAH) are the 4-5 ring PAH found preferentially adsorbed to the fine particles (<2.54u in urban ambient air and personal air. Personal exposure to the carcinogenic particle bound PAH is also highly correlated ...

EXPRESSION OF AS3MT ALTERS TRANSCRIPTIONAL PROFILES IN HUMAN UROTHELIAL CELLS EXPOSED TO ARSENITE

EPA Science Inventory

Inorganic arsenic (iAs) is an environmental toxin and human carcinogen. The enzymatic methylation of iAs that is catalyzed by arsenic (+3 oxidation state)-methyltransferase (AS3MT) generates reactive methylated intermediates that contribute to the toxic and carcinogenic effects ...

Reducing the use of carcinogens: the Massachusetts experience.

PubMed

Jacobs, Molly M; Massey, Rachel I; Tenney, Heather; Harriman, Elizabeth

2014-01-01

Toxics use reduction (TUR) is one part of a comprehensive cancer prevention strategy. TUR emphasizes reducing the use of cancer-causing chemicals by improving manufacturing processes and identifying and adopting safer alternatives. This analysis draws on 20 years of data collected from industries reporting to the Massachusetts Toxics Use Reduction Act (TURA) program to assess trends in the use and release of chemicals associated with cancer. We used a master list of known and suspected carcinogens developed from authoritative sources and a list of carcinogens grouped by their association with 11 cancer sites to analyze trends in use and release of chemicals by industrial facilities reporting to the TURA program from 1990 to 2010. The trend analysis shows that reported use and releases of carcinogens by these Massachusetts companies have decreased dramatically over time. Reported use declined 32% from 1990 to 2010, and reported releases declined 93% from 1991 to 2010 (1991 is when additional industrial sectors, including electric utilities, were phased into the program). Particularly large reductions were achieved in the use of trichloroethylene, perchloroethylene and cadmium and cadmium compounds. The analysis of groups of chemicals associated with specific cancer sites shows similar trends. Important opportunities for further reductions in many carcinogens, including formaldehyde, hexavalent chromium, and a variety of halogenated compounds are identified. Continued work to minimize the use of carcinogens can help to reduce the burden of cancer in Massachusetts and elsewhere.

Toxicity and carcinogenicity of potassium bromate--a new renal carcinogen

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kurokawa, Y.; Maekawa, A.; Takahashi, M.

Potassium bromate (KBrO3) is an oxidizing agent that has been used as a food additive, mainly in the bread-making process. Although adverse effects are not evident in animals fed bread-based diets made from flour treated with KBrO3, the agent is carcinogenic in rats and nephrotoxic in both man and experimental animals when given orally. It has been demonstrated that KBrO3 induces renal cell tumors, mesotheliomas of the peritoneum, and follicular cell tumors of the thyroid. In addition, experiments aimed at elucidating the mode of carcinogenic action have revealed that KBrO3 is a complete carcinogen, possessing both initiating and promoting activitiesmore » for rat renal tumorigenesis. However, the potential seems to be weak in mice and hamsters. In contrast to its weak mutagenic activity in microbial assays, KBrO3 showed relatively strong potential inducing chromosome aberrations both in vitro and in vivo. Glutathione and cysteine degrade KBrO3 in vitro; in turn, the KBrO3 has inhibitory effects on inducing lipid peroxidation in the rat kidney. Active oxygen radicals generated from KBrO3 were implicated in its toxic and carcinogenic effects, especially because KBrO3 produced 8-hydroxydeoxyguanosine in the rat kidney. A wide range of data from applications of various analytical methods are now available for risk assessment purposes.111 references.« less

Association of Metronidazole with Cancer: A Potential Risk Factor or Inconsistent Deductions?

PubMed

Adil, Muhammad; Iqbal, Waheed; Adnan, Fazal; Wazir, Shabnam; Khan, Imran; Khayam, Mohammad Umar; Kamal, Mohammad Amjad; Ahmad, Shafiq; Ahmad, Jawad; Khan, Ishaq N

2018-03-29

Metronidazole is a synthetic derivative of nitroimidazole that has been widely used for the treatment of several bacterial and protozoal parasitic infections including trichomoniasis, amoebiasis, giardiasis, liver abscess, acute ulcerative gingivitis, syphilis and tropical phagedena. In addition to its toxicity in the gastrointestinal tract and central/peripheral nervous system, metronidazole has been reported to cause mucosal imbalance by affecting the expression of mucin (Muc2 gene), which is responsible to form an insoluble mucous barrier that protects the gut lumen from microbial colonization. Since metronidazole is a nitro-group containing compound and used significantly for therapeutic purposes, scientists evaluated its carcinogenicity in different preclinical in-vitro and in-vivo studies. In addition to the preclinical in-vitro validation of DNA damage, metronidazole has been reported to induce cancer in the variety of animal models including lung cancer, malignant lymphomas, breast cancer, hepatocellular carcinoma, pituitary tumors, testicular neoplasms and uterine cancer. Several retrospective cohort studies have reported metronidazole as a potential risk factor for lung cancer (n = 771), cervical cancer (n = 2500), breast cancer (n = 2), cholangiocarcinoma (n = 1), and neuroblastoma (n = 28). So far, all the reported data have confirmed metronidazole carcinogenicity in animals; however, it is still controversial in humans. Based on previous observations, the oxidative metabolites from metronidazole metabolism are shown to have more carcinogenic effects than the parent drug itself. Since ~40% of drug metabolism is reliant on cytochromes, the inter-patient' differences in metronidazole metabolism potentially indicate the individual susceptibility to developing cancer. Due to these potent carcinogenic behaviors, use of metronidazole for animals treatment and its uses in animal food products are barred in the USA and European countries; however, its clinical use in human population is increasing. For this purpose, updated and improved research studies are required to explicate its mechanism/s involved in carcinogenesis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

40 CFR 261.11 - Criteria for listing hazardous waste.

Code of Federal Regulations, 2010 CFR

2010-07-01

... absence of data on human toxicity, it has been shown in studies to have an oral LD 50 toxicity (rat) of... liter, or a dermal LD 50 toxicity (rabbit) of less than 200 milligrams per kilogram or is otherwise... VIII only if they have been shown in scientific studies to have toxic, carcinogenic, mutagenic or...

40 CFR 261.11 - Criteria for listing hazardous waste.

Code of Federal Regulations, 2011 CFR

2011-07-01

... absence of data on human toxicity, it has been shown in studies to have an oral LD 50 toxicity (rat) of... liter, or a dermal LD 50 toxicity (rabbit) of less than 200 milligrams per kilogram or is otherwise... VIII only if they have been shown in scientific studies to have toxic, carcinogenic, mutagenic or...

1997 Toxic Hazards Research Annual Report

DTIC Science & Technology

1998-05-01

TYPE AND DATES COVERED I May 1998 Interim Report - October 1996-September 1997 4 . TITLE AND SUBTITLE 5. FUNDING NUMBERS 1997 Toxic Hazards Research... 4 3 TRICHLOROETHYLENE (TCE) CARCINOGENICITY PROJECT ......................... 7 3.1 SYNTHESIS AND...EXPERIMENTAL ERROR AND INTERINDIVIDUAL VARIABILITY .................. 20 J.Z. Byczkowski and J.C. Lipscomb 4 HALON REPLACEMENT TOXICITY PROJECT

Proteomic Assessment of Biochemical Pathways That Are Critical to Nickel-Induced Toxicity Responses in Human Epithelial Cells

EPA Science Inventory

Understanding the mechanisms underlying toxicity initiated by nickel, a ubiquitous environmental contaminant and known human carcinogen is necessary for proper assessment of its risks to human and environment. Among a variety of toxic mechanisms, disruption of protein responses a...

Role of Metabolism in Arsenic-Induced Toxicity: Identification and Quantification of Arsenic Metabolites in Tissues and Excreta

EPA Science Inventory

Arsenic is a known toxicant and carcinogen. Methylation of inorganic arsenic was once thought to be a detoxification mechanism because of the rapid excretion and relatively lower toxicity of the pentavalent organic arsenical metabolites. Advances in analytical chemistry have al...

Human health tradeoffs in wellhead drinking water treatment: Comparing exposure reduction to embedded life cycle risks.

PubMed

Gifford, Mac; Chester, Mikhail; Hristovski, Kiril; Westerhoff, Paul

2018-01-01

Treatment of drinking water decreases human health risks by reducing pollutants, but the required materials, chemicals, and energy emit pollutants and increase health risks. We explored human carcinogenic and non-carcinogenic disease tradeoffs of water treatment by comparing pollutant dose-response curves against life cycle burden using USEtox methodology. An illustrative wellhead sorbent groundwater treatment system removing hexavalent chromium or pentavalent arsenic serving 3200 people was studied. Reducing pollutant concentrations in drinking water from 20 μg L -1 to 10 μg L -1 avoided 37 potential cancer cases and 64 potential non-cancer disease cases. Human carcinogenicity embedded in treatment was 0.2-5.3 cases, and non-carcinogenic toxicity was 0.2-14.3 cases, depending on technology and degree of treatment. Embedded toxicity impacts from treating Cr(VI) using strong-base anion exchange were <10% of those from using weak base anion exchange. Acidification and neutralization contributed >90% of the toxicity impacts for treatment options requiring pH control. In scenarios where benefits exceeded burdens, tradeoffs still existed. Benefits are experienced by a local population but burdens are born externally where the materials and energy are produced, thus exporting the health risks. Even when burdens clearly exceeded benefits, cost considerations may still drive selecting a detrimental treatment level or technology. Copyright © 2017 Elsevier Ltd. All rights reserved.

Novel Uses of In Vitro Data to Develop Quantitative Biological Activity Relationship Models for in Vivo Carcinogenicity Prediction.

PubMed

Pradeep, Prachi; Povinelli, Richard J; Merrill, Stephen J; Bozdag, Serdar; Sem, Daniel S

2015-04-01

The availability of large in vitro datasets enables better insight into the mode of action of chemicals and better identification of potential mechanism(s) of toxicity. Several studies have shown that not all in vitro assays can contribute as equal predictors of in vivo carcinogenicity for development of hybrid Quantitative Structure Activity Relationship (QSAR) models. We propose two novel approaches for the use of mechanistically relevant in vitro assay data in the identification of relevant biological descriptors and development of Quantitative Biological Activity Relationship (QBAR) models for carcinogenicity prediction. We demonstrate that in vitro assay data can be used to develop QBAR models for in vivo carcinogenicity prediction via two case studies corroborated with firm scientific rationale. The case studies demonstrate the similarities between QBAR and QSAR modeling in: (i) the selection of relevant descriptors to be used in the machine learning algorithm, and (ii) the development of a computational model that maps chemical or biological descriptors to a toxic endpoint. The results of both the case studies show: (i) improved accuracy and sensitivity which is especially desirable under regulatory requirements, and (ii) overall adherence with the OECD/REACH guidelines. Such mechanism based models can be used along with QSAR models for prediction of mechanistically complex toxic endpoints. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

78 FR 15913 - Addition of ortho-Nitrotoluene; Community Right-to-Know Toxic Chemical Release Reporting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-13

... 12th Report on Carcinogens as ``reasonably anticipated to be a human carcinogen.'' EPA believes that o... cancer in humans. Based on a review of the available production and use information, o-nitrotoluene is... can reasonably be anticipated to cause significant adverse acute human health effects at concentration...

Estrogenic status modulates aryl hydrocarbon receptor - mediated hepatic gene expression and carcinogenicity

USDA-ARS?s Scientific Manuscript database

Estrogenic status is thought to influence the cancer risk in women and has been reported to affect toxicity of carcinogenic polycyclic aromatic hydrocarbons (PAHs) in animals. The objective of this study was to examine the influence of estradiol (E2) on hepatic gene expression changes mediated by 7,...

Environmental Carcinogen Releases and Lung Cancer Mortality in Rural-Urban Areas of the United States

ERIC Educational Resources Information Center

Luo, Juhua; Hendryx, Michael

2011-01-01

Purpose: Environmental hazards are unevenly distributed across communities and populations; however, little is known about the distribution of environmental carcinogenic pollutants and lung cancer risk across populations defined by race, sex, and rural-urban setting. Methods: We used the Toxics Release Inventory (TRI) database to conduct an…

EXPRESSON OF AS3MT ALTERS TRANSCRIPTIONAL PROFILES IN HUMAN UROTHELIAL CELLS EXPOSED TO ARSENITE

EPA Science Inventory

Inorganic arsenic (iAs) is an environmental toxin and human carcinogen. The enzymatic methylation of iAs that is catalyzed by As (3+ oxidation state)-methyltransferase (AS3MT) generates reactive methyl-As intermediates that may contribute to the toxic or carcinogenic effects of i...

Bio-oils from biomass slow pyrolysis: a chemical and toxicological screening.

PubMed

Cordella, Mauro; Torri, Cristian; Adamiano, Alessio; Fabbri, Daniele; Barontini, Federica; Cozzani, Valerio

2012-09-15

Bio-oils were produced from bench-scale slow-pyrolysis of three different biomass samples (corn stalks, poplar and switchgrass). Experimental protocols were developed and applied in order to screen their chemical composition. Several hazardous compounds were detected in the bio-oil samples analysed, including phenols, furans and polycyclic aromatic hydrocarbons. A procedure was outlined and applied to the assessment of toxicological and carcinogenic hazards of the bio-oils. The following hazardous properties were considered: acute toxicity; ecotoxicity; chronic toxicity; carcinogenicity. Parameters related to these properties were quantified for each component identified in the bio-oils and overall values were estimated for the bio-oils. The hazard screening carried out for the three bio-oils considered suggested that: (i) hazards to human health could be associated with chronic exposures to the bio-oils; (ii) acute toxic effects on humans and eco-toxic effects on aquatic ecosystems could also be possible in the case of loss of containment; and (iii) bio-oils may present a marginal potential carcinogenicity. The approach outlined allows the collection of screening information on the potential hazards posed by the bio-oils. This can be particularly useful when limited time and analytical resources reduce the possibility to obtain detailed specific experimental data. Copyright © 2012 Elsevier B.V. All rights reserved.

Studies Update Vinyl Chloride Hazards.

ERIC Educational Resources Information Center

Rawls, Rebecca

1980-01-01

Extensive study affirms that vinyl chloride is a potent animal carcinogen. Epidemiological studies show elevated rates of human cancers in association with extended contact with the compound. (Author/RE)

COMMONALITIES IN METABOLISM OF ARSENICALS

EPA Science Inventory

Elucidating the pathway of inorganic arsenic metabolism shows that some of methylated arsenicals formed as intermediates and products are reactive and toxic species. Hence, methylated arsenicals likely mediate at least some of the toxic and carcinogenic effects associated with e...

An integrated approach for prospectively investigating a mode-of-action for rodent liver effects

DOE Office of Scientific and Technical Information (OSTI.GOV)

LeBaron, Matthew J., E-mail: MJLeBaron@dow.com; Geter, David R., E-mail: dave.geter@gmail.com; Rasoulpour, Reza J.

Registration of new plant protection products (e.g., herbicide, insecticide, or fungicide) requires comprehensive mammalian toxicity evaluation including carcinogenicity studies in two species. The outcome of the carcinogenicity testing has a significant bearing on the overall human health risk assessment of the substance and, consequently, approved uses for different crops across geographies. In order to understand the relevance of a specific tumor finding to human health, a systematic, transparent, and hypothesis-driven mode of action (MoA) investigation is, appropriately, an expectation by the regulatory agencies. Here, we describe a novel approach of prospectively generating the MoA data by implementing additional end pointsmore » to the standard guideline toxicity studies with sulfoxaflor, a molecule in development. This proactive MoA approach results in a more robust integration of molecular with apical end points while minimizing animal use. Sulfoxaflor, a molecule targeting sap-feeding insects, induced liver effects (increased liver weight due to hepatocellular hypertrophy) in an initial palatability probe study for selecting doses for subsequent repeat-dose dietary studies. This finding triggered the inclusion of dose-response investigations of the potential key events for rodent liver carcinogenesis, concurrent with the hazard assessment studies. As predicted, sulfoxaflor induced liver tumors in rats and mice in the bioassays. The MoA data available by the time of the carcinogenicity finding supported the conclusion that the carcinogenic potential of sulfoxaflor was due to CAR/PXR nuclear receptor activation with subsequent hepatocellular proliferation. This MoA was not considered to be relevant to humans as sulfoxaflor is unlikely to induce hepatocellular proliferation in humans and therefore would not be a human liver carcinogen. - Highlights: • We prospectively generated MoA data into standard guideline toxicity studies. • A proactive MoA approach integrates all end points while minimizing animal use. • MoA data predicted the rodent carcinogenicity of sulfoxaflor via CAR/PXR. • Liver MoA was considered not relevant to humans and hence not a human carcinogen.« less

Classifications for carcinogenesis of antitumoral drugs.

PubMed

Binetti, R; Costamagna, F M; Marcello, I

2003-12-01

The aim of this review is to support the medical staff engaged in tumor therapy with the carcinogenicity, mutagenicity, developmental toxicity classification of a large number of chemiotherapic drugs by national and international Agencies; it also gives their rationale and the few cases for which the classification varies among, for example, the European Union and the United States of America. A large list of such drugs, producers, commercial names, CAS numbers and chemical names is reported. This list is subject to changes for the quick development in this field: many drugs are retired and many more are introduced in clinical practice. The list is updated to the summer 2003 and retains many drugs which have more than one use or have limited use. The protection of the medical personnel using antitumor chemiotherapics can need retrospective epidemiological investigations and obsolete drugs are of importance for some of the past exposures.

Medical toxicology and public health-update on research and activities at the centers for disease control and prevention and the agency for toxic substances and disease registry.

PubMed

Snook, Curtis P; Cardarelli, John; Mickelsen, R Leroy; Mattorano, Dino; Nalipinski, Michael

2008-12-01

An extensive review of CDC epidemiological responses to human outbreaks of anthrax from occupational settings between the years of 1950 and 2001 documented a variety of approaches to mitigation and decontamination [2]. These approaches included taking no action, burning contaminated materials, chlorinating water supplies, instituting administrative and engineering controls and PPE, vaccinating potentially exposed individuals, and in 2 instances, fumigating with formaldehyde vapor (now considered to be a human carcinogen). Secondary contamination of a worker's home was documented in 1 case, but not felt to be clinically significant to warrant any decontamination efforts. In response to the B. anthracis attacks in 2001, chlorine dioxide fumigation, vaporous hydrogen peroxide fumigation, and a combination of HEPA vacuuming, cleaning, and bleach application were all techniques used successfully to clean B. anthracis spore contamination.

Induction of prophage lambda by chlorinated organics: Detection of some single-species/single-site carcinogens

DOE Office of Scientific and Technical Information (OSTI.GOV)

DeMarini, D.M.; Brooks, H.G.

1992-01-01

Twenty-eight chlorinated organic compounds were evaluated for their ability to induce DNA damage using the Microscreen prophage-induction assay in Escherichia coli. Comparison of the performance characteristics of the prophage-induction and Salmonella assays to rodent carcinogenicity assays showed that the prophage-induction assay had a somewhat higher specificity than did the Salmonella assay (70% vs. 50%); sensitivity, concordance, and positive and negative predictivity were similar for the two microbial assays. The Microscreen prophage-induction assay failed to detect eight carcinogens, perhaps due to toxicity or other unknown factors; five of these eight carcinogens were detected by the Salmonella assay. However, the prophage-induction assaymore » did detect six carcinogens that were not detected by the Salmonella assay, and five of these were single-species, single-site carcinogens, mostly mouse liver carcinogens. Some of these carcinogens, such as the chloroethanes, produce free radicals, which may be the basis for their carcinogenicity and ability to induce prophage. The prophage-induction (or other SOS) assay may be useful in identifying some genotoxic chlorinated carcinogens that induce DNA damage that do not revert the standard Salmonella tester strains.« less

CarcinoPred-EL: Novel models for predicting the carcinogenicity of chemicals using molecular fingerprints and ensemble learning methods.

PubMed

Zhang, Li; Ai, Haixin; Chen, Wen; Yin, Zimo; Hu, Huan; Zhu, Junfeng; Zhao, Jian; Zhao, Qi; Liu, Hongsheng

2017-05-18

Carcinogenicity refers to a highly toxic end point of certain chemicals, and has become an important issue in the drug development process. In this study, three novel ensemble classification models, namely Ensemble SVM, Ensemble RF, and Ensemble XGBoost, were developed to predict carcinogenicity of chemicals using seven types of molecular fingerprints and three machine learning methods based on a dataset containing 1003 diverse compounds with rat carcinogenicity. Among these three models, Ensemble XGBoost is found to be the best, giving an average accuracy of 70.1 ± 2.9%, sensitivity of 67.0 ± 5.0%, and specificity of 73.1 ± 4.4% in five-fold cross-validation and an accuracy of 70.0%, sensitivity of 65.2%, and specificity of 76.5% in external validation. In comparison with some recent methods, the ensemble models outperform some machine learning-based approaches and yield equal accuracy and higher specificity but lower sensitivity than rule-based expert systems. It is also found that the ensemble models could be further improved if more data were available. As an application, the ensemble models are employed to discover potential carcinogens in the DrugBank database. The results indicate that the proposed models are helpful in predicting the carcinogenicity of chemicals. A web server called CarcinoPred-EL has been built for these models ( http://ccsipb.lnu.edu.cn/toxicity/CarcinoPred-EL/ ).

Toxicity and carcinogenicity of potassium bromate--a new renal carcinogen.

PubMed Central

Kurokawa, Y; Maekawa, A; Takahashi, M; Hayashi, Y

1990-01-01

Potassium bromate (KBrO3) is an oxidizing agent that has been used as a food additive, mainly in the bread-making process. Although adverse effects are not evident in animals fed bread-based diets made from flour treated with KBrO3, the agent is carcinogenic in rats and nephrotoxic in both man and experimental animals when given orally. It has been demonstrated that KBrO3 induces renal cell tumors, mesotheliomas of the peritoneum, and follicular cell tumors of the thyroid. In addition, experiments aimed at elucidating the mode of carcinogenic action have revealed that KBrO3 is a complete carcinogen, possessing both initiating and promoting activities for rat renal tumorigenesis. However, the potential seems to be weak in mice and hamsters. In contrast to its weak mutagenic activity in microbial assays, KBrO3 showed relatively strong potential inducing chromosome aberrations both in vitro and in vivo. Glutathione and cysteine degrade KBrO3 in vitro; in turn, the KBrO3 has inhibitory effects on inducing lipid peroxidation in the rat kidney. Active oxygen radicals generated from KBrO3 were implicated in its toxic and carcinogenic effects, especially because KBrO3 produced 8-hydroxydeoxyguanosine in the rat kidney. A wide range of data from applications of various analytical methods are now available for risk assessment purposes. Images FIGURE 1. FIGURE 2. FIGURE 5. FIGURE 6. FIGURE 7. FIGURE 8. FIGURE 9. FIGURE 10. FIGURE 11. FIGURE 12. PMID:2269236

[Health risk assessment of coke oven PAHs emissions].

PubMed

Bo, Xin; Wang, Gang; Wen, Rou; Zhao, Chun-Li; Wu, Tie; Li, Shi-Bei

2014-07-01

Polycyclic aromatic hydrocarbons (PAHs) produced by coke oven are with strong toxicity and carcinogenicity. Taken typical coke oven of iron and steel enterprises as the case study, the dispersion and migration of 13 kinds of PAHs emitted from coke oven were analyzed using AERMOD dispersion model, the carcinogenic and non-carcinogenic risks at the receptors within the modeling domain were evaluated using BREEZE Risk Analyst and the Human Health Risk Assessment Protocol for Hazardous Waste Combustion (HHRAP) was followed, the health risks caused by PAHs emission from coke oven were quantitatively evaluated. The results indicated that attention should be paid to the non-carcinogenic risk of naphthalene emission (the maximum value was 0.97). The carcinogenic risks of each single pollutant were all below 1.0E-06, while the maximum value of total carcinogenic risk was 2.65E-06, which may have some influence on the health of local residents.

Micro-total envelope system with silicon nanowire separator for safe carcinogenic chemistry.

PubMed

Singh, Ajay K; Ko, Dong-Hyeon; Vishwakarma, Niraj K; Jang, Seungwook; Min, Kyoung-Ik; Kim, Dong-Pyo

2016-02-26

Exploration and expansion of the chemistries involving toxic or carcinogenic reagents are severely limited by the health hazards their presence poses. Here, we present a micro-total envelope system (μ-TES) and an automated total process for the generation of the carcinogenic reagent, its purification and its utilization for a desired synthesis that is totally enveloped from being exposed to the carcinogen. A unique microseparator is developed on the basis of SiNWs structure to replace the usual exposure-prone distillation in separating the generated reagent. Chloromethyl methyl ether chemistry is explored as a carcinogenic model in demonstrating the efficiency of the μ-TES that is fully automated so that feeding the ingredients for the generation is all it takes to produce the desired product. Syntheses taking days can be accomplished safely in minutes with excellent yields, which bodes well for elevating the carcinogenic chemistry to new unexplored dimensions.

[Application of quantum-chemical methods to prediction of the carcinogenicity of chemical substances].

PubMed

Zholdikova, Z I; Kharchevnikova, N V

2006-01-01

A version of logical-combinatorial JSM type intelligent system was used to predict the presence and the degree of a carcinogenic effect. This version was based on combined description of chemical substances including both structural and numeric parameters. The new version allows for the fact that the toxicity and danger caused by chemical substances often depend on their biological activation in the organism. The authors substantiate classifying chemicals according to their carcinogenic activity, and illustrate the use of the system to predict the carcinogenicity of polycyclic aromatic hydrocarbons using a model of bioactivation via the formation of diolepoxides, and the carcinogenicity of halogenated alkanes using a model of bioactivation via oxidative dehalogenation. The paper defined the boundary level of an energetic parameter, the exceeding of which correlated with the inhibition of halogenated alkanes's metabolism and the absence of carcinogenic activity.

Toxic Chemicals Use in School Labs Examined.

ERIC Educational Resources Information Center

Chemical and Engineering News, 1982

1982-01-01

The Consumer Product Safety Commission will recommend an information network to inform students and teachers of current toxicity evaluations of chemicals and of possible use of less hazardous substitutes. Lists names of 33 suspected carcinogens and 11 suspected teratogens. (SK)

Dehydropyrrolizidine alkaloid toxicity, cytotoxicity, and carcinogenicity

USDA-ARS?s Scientific Manuscript database

Dehyro-pyrrolizidine alkaloid (PA)-containing plants compose about 5% of the world’s flowering plants and they commonly poison livestock, wildlife and humans. Previous work has produced considerable understanding of PA toxicity, species susceptibility, conditions and routes of exposure, toxin metab...

Linking Arsenic Metabolism and Toxic Effects

EPA Science Inventory

Although arsenic has been long recognized as a toxicant and a carcinogen, the molecular basis for few of its adverse effects are well understood. Like other metalloids, arsenic undergoes extensive metabolism involving oxidation state changes and formation of methyl-arsenic bonds ...

Sucralose Non-Carcinogenicity: A Review of the Scientific and Regulatory Rationale

PubMed Central

Berry, Colin; Brusick, David; Cohen, Samuel M.; Hardisty, Jerry F.; Grotz, V. Lee; Williams, Gary M.

2016-01-01

ABSTRACT Regulatory authorities worldwide have found the nonnutritive sweetener, sucralose, to be noncarcinogenic, based on a range of studies. A review of these and other studies found through a comprehensive search of electronic databases, using appropriate key terms, was conducted and results of that review are reported here. An overview of the types of studies relied upon by regulatory agencies to assess carcinogenicity potential is also provided as context. Physiochemical and pharmacokinetic/toxicokinetic studies confirm stability under conditions of use and reveal no metabolites of carcinogenic potential. In vitro and in vivo assays reveal no confirmed genotoxic activity. Long-term carcinogenicity studies in animal models provide no evidence of carcinogenic potential for sucralose. In studies in healthy adults, sucralose was well-tolerated and without evidence of toxicity or other changes that might suggest a potential for carcinogenic effects. In summary, sucralose does not demonstrate carcinogenic activity even when exposure levels are several orders of magnitude greater than the range of anticipated daily ingestion levels. PMID:27652616

Sucralose Non-Carcinogenicity: A Review of the Scientific and Regulatory Rationale.

PubMed

Berry, Colin; Brusick, David; Cohen, Samuel M; Hardisty, Jerry F; Grotz, V Lee; Williams, Gary M

2016-01-01

Regulatory authorities worldwide have found the nonnutritive sweetener, sucralose, to be noncarcinogenic, based on a range of studies. A review of these and other studies found through a comprehensive search of electronic databases, using appropriate key terms, was conducted and results of that review are reported here. An overview of the types of studies relied upon by regulatory agencies to assess carcinogenicity potential is also provided as context. Physiochemical and pharmacokinetic/toxicokinetic studies confirm stability under conditions of use and reveal no metabolites of carcinogenic potential. In vitro and in vivo assays reveal no confirmed genotoxic activity. Long-term carcinogenicity studies in animal models provide no evidence of carcinogenic potential for sucralose. In studies in healthy adults, sucralose was well-tolerated and without evidence of toxicity or other changes that might suggest a potential for carcinogenic effects. In summary, sucralose does not demonstrate carcinogenic activity even when exposure levels are several orders of magnitude greater than the range of anticipated daily ingestion levels.

Bentonite toxicology and epidemiology - a review.

PubMed

Maxim, L Daniel; Niebo, Ron; McConnell, Ernest E

2016-11-01

Bentonite, a clay with numerous industrial and consumer applications, is mined and processed in many countries of the world. Its many beneficial uses also create the potential for widespread occupational and consumer exposure. The available studies on toxicity and epidemiology indicate that the principal exposure pathway of concern is inhalation of respirable dust by occupationally exposed cohorts. Bentonite itself is probably not more toxic than any other particulate not otherwise regulated and is not classified as a carcinogen by any regulatory or advisory body, but some bentonite may contain variable amounts of respirable crystalline silica, a recognized human carcinogen. Therefore, prudent management and adherence to occupational exposure limits is appropriate. This review summarizes the literature available on production, applications, exposure, toxicity, and epidemiology of bentonite and identifies data gaps and limitations.

Approaches to evaluating the toxicity and carcinogenicity of man-made fibers: summary of a workshop held November 11-13, 1991, Durham, North Carolina.

PubMed

McClellan, R O; Miller, F J; Hesterberg, T W; Warheit, D B; Bunn, W B; Kane, A B; Lippmann, M; Mast, R W; McConnell, E E; Reinhardt, C F

1992-12-01

The Workshop on Approaches to Evaluating the Toxicity and Carcinogenicity of Man-Made Fibers (MMF) was held in Durham, North Carolina, on November 11-13, 1991. The goal of the workshop was to reach a consensus, or to determine the extent to which a consensus existed, in two areas. Participants were asked to identify scientifically sound approaches for evaluating the toxicity and carcinogenicity of man-made fibers based on today's science and to determine research appropriate for study during the next 5 years that can provide an improved scientific basis for future revisions of approaches used to evaluate man-made fiber toxicity and carcinogenicity. During the first day, a series of "state of knowledge" presentations were made to provide all participants with a common data base from which to interact and discuss scientific issues. The workshop participants were assigned to one of four discussion groups, which met separately in three half-day sessions following the first day of presentations. All groups discussed the same topics: exposure assessment, hazard identification, and dose-response information needed to integrate to characterize risk in the first session; approaches to obtaining the needed information in the second session; and recommended approaches and guidelines for evaluating the toxicity and carcinogenicity of MMF and research needs in the third session. The workshop participants reconvened as a whole after each discussion session, and one member from each group reported the group's conclusions. A closure period was also included at the end of the workshop for review and discussion of items that had been considered during the workshop. The primary conclusions reached were the following: -All fiber types capable of depositing in the thorax are not alike in their pathogenic potential. -Only fiber samples with dimensions similar to those to which humans can inhale should be tested. -A complete characterization (i.e., dimensions, fiber number, mass, and aerodynamic diameter) of the fiber aerosol and retained dose is essential. -Appropriate aerosol generation methods must be used for inhalation studies in order to preserve fiber lengths. -A tiered approach to toxicity evaluation is recommended that includes: 1. In vitro screening for durability, surface properties, cytotoxicity, and similar properties, etc; 2. Short-term inhalation or other in vivo studies; 3. That chronic inhalation studies are the "gold standard" (i.e., provide most appropriate data for risk characterization). -The rat is the most appropriate species for inhalation studies. -In chronic inhalation studies, animals should be retained to at least 20% survival after 2-year exposure. -Serial lung burden analyses are an essential component of inhalation studies and are essential for understanding exposure-dose-response relationships. -Studies oriented to understanding mechanisms of toxicity and carcinogenicity are important adjuncts to traditional toxicity studies. -Histopathological analyses of tissues of the respiratory tract represent primary endpoints for evaluating effects of inhaled fibers. Major effects include pulmonary fibrosis, lung tumors, and mesotheliomas. Experimental tissues should be archived for future studies; wherever possible, handling and preservation of tissues should be done in a way that maximizes their future use in mechanistic studies. -Potential human exposures throughout the entire life-cycle of the fiber must be considered and fibrous material for toxicologic studies prepared accordingly. -Intracavity studies are inappropriate for risk characterization but can play a useful screening role in assessing fiber toxicity.(ABSTRACT TRUNCATED AT 400 WORDS)

Hazard Classification of Household Chemical Products in Korea according to the Globally Harmonized System of Classification and labeling of Chemicals.

PubMed

Kim, Kyung-Hee; Song, Dae-Jong; Yu, Myeong-Hyun; Park, Yuon-Shin; Noh, Hye-Ran; Kim, Hae-Joon; Choi, Jae-Wook

2013-07-16

This study was conducted to review the validity of the need for the application of the Globally Harmonized System of Classification and Labeling of Chemicals (GHS) to household chemical products in Korea. The study also aimed to assess the severity of health and environmental hazards of household chemical products using the GHS. 135 products were classified as 'cleaning agents and polishing agents' and 98 products were classified as 'bleaches, disinfectants, and germicides.' The current status of carcinogenic classification of GHS and carcinogenicity was examined for 272 chemical substances contained in household chemical products by selecting the top 11 products for each of the product categories. In addition, the degree of toxicity was assessed through analysis of whether the standard of the Republic of Korea's regulations on household chemical products had been exceeded or not. According to GHS health and environmental hazards, "acute toxicity (oral)" was found to be the highest for two product groups, 'cleaning agents and polishing agents', and 'bleaches, disinfectants, and germicides' (result of classification of 233 household chemical products) at 37.8% and 52.0% respectively. In an analysis of carcinogenicity assuming a threshold of IARC 2B for the substances in household chemical products, we found 'cleaning agents and polishing agents' to contain 12 chemical substances and 'bleaches, disinfectants, and germicides' 11 chemical substances. Some of the household chemical products were found to have a high hazard level including acute toxicity and germ cell mutagenicity, carcinogenicity, and reproductive toxicity. Establishing a hazard information delivery system including the application of GHS to household chemical products in Korea is urgent as well.

Hazard Classification of Household Chemical Products in Korea according to the Globally Harmonized System of Classification and labeling of Chemicals

PubMed Central

2013-01-01

Objectives This study was conducted to review the validity of the need for the application of the Globally Harmonized System of Classification and Labeling of Chemicals (GHS) to household chemical products in Korea. The study also aimed to assess the severity of health and environmental hazards of household chemical products using the GHS. Methods 135 products were classified as ‘cleaning agents and polishing agents’ and 98 products were classified as ‘bleaches, disinfectants, and germicides.’ The current status of carcinogenic classification of GHS and carcinogenicity was examined for 272 chemical substances contained in household chemical products by selecting the top 11 products for each of the product categories. In addition, the degree of toxicity was assessed through analysis of whether the standard of the Republic of Korea’s regulations on household chemical products had been exceeded or not. Results According to GHS health and environmental hazards, “acute toxicity (oral)” was found to be the highest for two product groups, ‘cleaning agents and polishing agents’, and ‘bleaches, disinfectants, and germicides’ (result of classification of 233 household chemical products) at 37.8% and 52.0% respectively. In an analysis of carcinogenicity assuming a threshold of IARC 2B for the substances in household chemical products, we found ‘cleaning agents and polishing agents’ to contain 12 chemical substances and ‘bleaches, disinfectants, and germicides’ 11 chemical substances. Conclusion Some of the household chemical products were found to have a high hazard level including acute toxicity and germ cell mutagenicity, carcinogenicity, and reproductive toxicity. Establishing a hazard information delivery system including the application of GHS to household chemical products in Korea is urgent as well. PMID:24472347

POTASSIUM BROMATE-INDUCED RAT CLEAR CELL RENAL TUMOR IS INDEPENDENT OF CODING REGION MUTATIONS IN THE VON HIPPEL- LINDAU GENE

EPA Science Inventory

Potassium bromate (KBr03) is a rat renal carcinogen and a major drinking water disinfection by-product from ozonization. While KBr03 is a human nephro- and neuro-toxicant, its carcinogenicity in humans is unknown. Clear cell renal tumors, the common form of human renal carcinomas...

The carcinogenicity of chromium

PubMed Central

Norseth, Tor

1981-01-01

The carcinogenicity of chromium compounds is reviewed with specific attention to the gaps in knowledge for risk estimation and research needs. The most important problems at present are whether trivalent chromium compounds cause cancer, and whether there is a difference in cancer causing effects between the soluble and the slightly soluble hexavalent compounds in the practical exposure situation. Dose estimates for risk estimation based on epidemiological investigations are also lacking. Present evidence indicates that the trivalent chromium compounds do not cause cancer although high concentrations in some in vitro systems have shown genetic toxicity. Hexavalent chromium compounds cause cancer in humans, in experimental animals and exert genetic toxicity in bacteria and in mammalian cells in vitro. Epidemiological evidence and animal experiments indicate that the slightly soluble hexavalent salts are the most potent carcinogens, but proper identification and characterization of exposure patterns in epidemiological work are lacking. Workers also tend to have mixed exposures. Soluble and slightly soluble salts are equally potent genotoxic agents in vitro. Further work for establishing dose estimates for risk evaluation in epidemiological work is important. In vitro systems should be applied for further identification of the mechanism of the carcinogenic effects, and animal experiments are urgent for comparison of the carcinogenic potency of the different hexavalent salts. Hexavalent chromium salts must be regarded as established carcinogens, and proper action should be taken in all industries with regard to such exposure. At present the carcinogenic risk to the general population caused by chromium compounds seems to be negligible, chromium in cigarettes, however, is an uncertainty in this respect. The amount of chromium and the type of chromium compounds inhaled from cigarettes is not known. PMID:7023928

Formaldehyde: a candidate toxic air contaminant. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frye, B.; Parker, T.

1988-03-01

Formaldehyde (HCHO) is a gas widely used in adhesives and resins, textiles, embalming fluids, fungicides, air fresheners, and cosmetics. It is directly emitted into the ambient outdoor air from vehicular and stationary sources, and is also produced in the atmosphere from other substances by photochemical smog processes. The International Agency for Research on Cancer (IARC) has determined that there is sufficient evidence for carcinogenicity of formaldehyde to animals, and limited evidence for carcinogenicity to humans. EPA classifies formaldehyde as a probable human carcinogen with a one in a million risk concentration of 0.08 ppb.

DISTRIBUTED STRUCTURE-SEARCHABLE TOXICITY (DSSTOX) PUBLIC DATABASE NETWORK: A PROPOSAL

EPA Science Inventory

The ability to assess the potential genotoxicity, carcinogenicity, or other toxicity of pharmaceutical or industrial chemicals based on chemical structure information is a highly coveted and shared goal of varied academic, commercial, and government regulatory groups. These dive...

Leaching characteristics, ecotoxicity, and risk assessment based management of mine wastes

NASA Astrophysics Data System (ADS)

Kim, J.; Ju, W. J.; Jho, E. H.; Nam, K.; Hong, J. K.

2016-12-01

Mine wastes generated during mining activities in metal mines generally contain high concentrations of metals that may impose toxic effects to surrounding environment. Thus, it is necessary to properly assess the mining-impacted landscapes for management. The study investigated leaching characteristics, potential environmental effects, and human health risk of mine wastes from three different metal mines in South Korea (molybdenum mine, lead-zinc mine, and magnetite mine). The heavy metal concentrations in the leachates obtained by using the Korean Standard Test Method for Solid Wastes (STM), Toxicity Characteristics Leaching Procedure (TCLP), and Synthetic Precipitation Leaching Procedure (SPLP) met the Korea Waste Control Act and the USEPA region 3 regulatory levels accordingly, even though the mine wastes contained high concentrations of metals. Assuming that the leachates may get into nearby water sources, the leachate toxicity was tested using Daphnia Magna. The toxic unit (TU) values after 24 h and 48 h exposure of all the mine wastes tested met the Korea Allowable Effluent Water Quality Standards (TU<1). The column leaching test showed that the lead-zinc mine waste may have long-term toxic effects (TU>1 for the eluent at L/S of 30) implying that the long-term effect of mine wastes left in mining areas need to be assessed. Considering reuse of mine wastes as a way of managing mine wastes, the human health risk assessment of reusing the lead-zinc mine waste in industrial areas was carried out using the bioavailable fraction of the heavy metals contained in the mine wastes, which was determined by using the Solubility/Bioavailability Research Consortium method. There may be potential carcinogenic risk (9.7E-05) and non-carcinogenic risk (HI, Hazard Index of 1.0E+00) as CR≧1.0E-05 has carcinogenic risk and HI≧1.0E+00 has non-carcinogenic risk. Overall, this study shows that not only the concentration-based assessment but ecological toxic effect and human health risk based assessments can be utilized for mining-impacted landscapes management.

Exposure to Nicotine and Selected Toxicants in Cigarette Smokers Who Switched to Electronic Cigarettes: A Longitudinal Within-Subjects Observational Study

PubMed Central

Gawron, Michal; Smith, Danielle M.; Peng, Margaret; Jacob, Peyton; Benowitz, Neal L.

2017-01-01

Introduction: Electronic cigarettes (e-cigarettes) are purported to deliver nicotine aerosol without any toxic combustion products present in tobacco smoke. In this longitudinal within-subjects observational study, we evaluated the effects of e-cigarettes on nicotine delivery and exposure to selected carcinogens and toxicants. Methods: We measured seven nicotine metabolites and 17 tobacco smoke exposure biomarkers in the urine samples of 20 smokers collected before and after switching to pen-style M201 e-cigarettes for 2 weeks. Biomarkers were metabolites of 13 major carcinogens and toxicants in cigarette smoke: one tobacco-specific nitrosamine (NNK), eight volatile organic compounds (1,3-butadiene, crotonaldehyde, acrolein, benzene, acrylamide, acrylonitrile, ethylene oxide, and propylene oxide), and four polycyclic aromatic hydrocarbons (naphthalene, fluorene, phenanthrene, and pyrene). Changes in urine biomarkers concentration were tested using repeated measures analysis of variance. Results: In total, 45% of participants reported complete abstinence from cigarette smoking at 2 weeks, while 55% reported continued smoking. Levels of total nicotine and some polycyclic aromatic hydrocarbon metabolites did not change after switching from tobacco to e-cigarettes. All other biomarkers significantly decreased after 1 week of using e-cigarettes (p < .05). After 1 week, the greatest percentage reductions in biomarkers levels were observed for metabolites of 1,3-butadiene, benzene, and acrylonitrile. Total NNAL, a metabolite of NNK, declined by 57% and 64% after 1 and 2 weeks, respectively, while 3-hydroxyfluorene levels declined by 46% at week 1, and 34% at week 2. Conclusions: After switching from tobacco to e-cigarettes, nicotine exposure remains unchanged, while exposure to selected carcinogens and toxicants is substantially reduced. Implications: To our knowledge, this is the first study that demonstrates that substituting tobacco cigarettes with an e-cigarette may reduce user exposure to numerous toxicants and carcinogens otherwise present in tobacco cigarettes. Data on reduced exposure to harmful constituents that are present in tobacco cigarettes and e-cigarettes can aid in evaluating e-cigarettes as a potential harm reduction device. PMID:27613896

Exposure to Nicotine and Selected Toxicants in Cigarette Smokers Who Switched to Electronic Cigarettes: A Longitudinal Within-Subjects Observational Study.

PubMed

Goniewicz, Maciej L; Gawron, Michal; Smith, Danielle M; Peng, Margaret; Jacob, Peyton; Benowitz, Neal L

2017-02-01

Electronic cigarettes (e-cigarettes) are purported to deliver nicotine aerosol without any toxic combustion products present in tobacco smoke. In this longitudinal within-subjects observational study, we evaluated the effects of e-cigarettes on nicotine delivery and exposure to selected carcinogens and toxicants. We measured seven nicotine metabolites and 17 tobacco smoke exposure biomarkers in the urine samples of 20 smokers collected before and after switching to pen-style M201 e-cigarettes for 2 weeks. Biomarkers were metabolites of 13 major carcinogens and toxicants in cigarette smoke: one tobacco-specific nitrosamine (NNK), eight volatile organic compounds (1,3-butadiene, crotonaldehyde, acrolein, benzene, acrylamide, acrylonitrile, ethylene oxide, and propylene oxide), and four polycyclic aromatic hydrocarbons (naphthalene, fluorene, phenanthrene, and pyrene). Changes in urine biomarkers concentration were tested using repeated measures analysis of variance. In total, 45% of participants reported complete abstinence from cigarette smoking at 2 weeks, while 55% reported continued smoking. Levels of total nicotine and some polycyclic aromatic hydrocarbon metabolites did not change after switching from tobacco to e-cigarettes. All other biomarkers significantly decreased after 1 week of using e-cigarettes (p < .05). After 1 week, the greatest percentage reductions in biomarkers levels were observed for metabolites of 1,3-butadiene, benzene, and acrylonitrile. Total NNAL, a metabolite of NNK, declined by 57% and 64% after 1 and 2 weeks, respectively, while 3-hydroxyfluorene levels declined by 46% at week 1, and 34% at week 2. After switching from tobacco to e-cigarettes, nicotine exposure remains unchanged, while exposure to selected carcinogens and toxicants is substantially reduced. To our knowledge, this is the first study that demonstrates that substituting tobacco cigarettes with an e-cigarette may reduce user exposure to numerous toxicants and carcinogens otherwise present in tobacco cigarettes. Data on reduced exposure to harmful constituents that are present in tobacco cigarettes and e-cigarettes can aid in evaluating e-cigarettes as a potential harm reduction device. © The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Hexavalent Chromium Is Carcinogenic to F344/N Rats and B6C3F1 Mice after Chronic Oral Exposure

PubMed Central

Stout, Matthew D.; Herbert, Ronald A.; Kissling, Grace E.; Collins, Bradley J.; Travlos, Gregory S.; Witt, Kristine L.; Melnick, Ronald L.; Abdo, Kamal M.; Malarkey, David E.; Hooth, Michelle J.

2009-01-01

Background Hexavalent chromium [Cr(VI)] is a human carcinogen after inhalation exposure. Humans also ingest Cr(VI) from contaminated drinking water and soil; however, limited data exist on the oral toxicity and carcinogenicity of Cr(VI). Objective We characterized the chronic oral toxicity and carcinogenicity of Cr(VI) in rodents. Methods The National Toxicology Program (NTP) conducted 2-year drinking water studies of Cr(VI) (as sodium dichromate dihydrate) in male and female F344/N rats and B6C3F1 mice. Results Cr(VI) exposure resulted in increased incidences of rare neoplasms of the squamous epithelium that lines the oral cavity (oral mucosa and tongue) in male and female rats, and of the epithelium lining the small intestine in male and female mice. Cr(VI) exposure did not affect survival but resulted in reduced mean body weights and water consumption, due at least in part to poor palatability of the dosed water. Cr(VI) exposure resulted in transient microcytic hypochromic anemia in rats and microcytosis in mice. Nonneoplastic lesions included diffuse epithelial hyperplasia in the duodenum and jejunum of mice and histiocytic cell infiltration in the duodenum, liver, and mesenteric and pancreatic lymph nodes of rats and mice. Conclusions Cr(VI) was carcinogenic after administration in drinking water to male and female rats and mice. PMID:19479012

Glyphosate toxicity and carcinogenicity: a review of the scientific basis of the European Union assessment and its differences with IARC.

PubMed

Tarazona, Jose V; Court-Marques, Daniele; Tiramani, Manuela; Reich, Hermine; Pfeil, Rudolf; Istace, Frederique; Crivellente, Federica

2017-08-01

Glyphosate is the most widely used herbicide worldwide. It is a broad spectrum herbicide and its agricultural uses increased considerably after the development of glyphosate-resistant genetically modified (GM) varieties. Since glyphosate was introduced in 1974, all regulatory assessments have established that glyphosate has low hazard potential to mammals, however, the International Agency for Research on Cancer (IARC) concluded in March 2015 that it is probably carcinogenic. The IARC conclusion was not confirmed by the EU assessment or the recent joint WHO/FAO evaluation, both using additional evidence. Glyphosate is not the first topic of disagreement between IARC and regulatory evaluations, but has received greater attention. This review presents the scientific basis of the glyphosate health assessment conducted within the European Union (EU) renewal process, and explains the differences in the carcinogenicity assessment with IARC. Use of different data sets, particularly on long-term toxicity/carcinogenicity in rodents, could partially explain the divergent views; but methodological differences in the evaluation of the available evidence have been identified. The EU assessment did not identify a carcinogenicity hazard, revised the toxicological profile proposing new toxicological reference values, and conducted a risk assessment for some representatives uses. Two complementary exposure assessments, human-biomonitoring and food-residues-monitoring, suggests that actual exposure levels are below these reference values and do not represent a public concern.

Occurrence of Pineal Gland Tumors in Combined Chronic Toxicity/Carcinogenicity Studies in Wistar Rats.

PubMed

Treumann, Silke; Buesen, Roland; Gröters, Sibylle; Eichler, Jens-Olaf; van Ravenzwaay, Bennard

2015-08-01

Pineal gland tumors are very rare brain lesions in rats as well as in other species including humans. A total of 8 (out of 1,360 examined) Wistar rats from 3 different combined chronic toxicity/carcinogenicity or mere carcinogenicity studies revealed pineal gland tumors. The tumors were regarded to be spontaneous and unrelated to treatment. The morphology and immunohistochemical evaluation led to the diagnosis malignant pinealoma. The main characteristics that were variably developed within the tumors were the following: cellular atypia, high mitotic index, giant cells, necrosis, Homer Wright rosettes, Flexner-Wintersteiner rosettes and pseudorosettes, positive immunohistochemical reaction for synaptophysin, and neuron-specific enolase. The pineal gland is not a protocol organ for histopathological examination in carcinogenicity studies. Nevertheless, the pineal gland can occasionally be encountered on the routine brain section or if it is the origin of a tumor protruding into the brain, the finding will be recorded. Therefore, although known to be a rare tumor in rats, pineal neoplasms should be included in the list of possible differential diagnoses for brain tumors, especially when the tumor is located in the region of the pineal body. © 2015 by The Author(s).

Estimation of Carcinogenicity using Hierarchical Clustering and Nearest Neighbor Methodologies

EPA Science Inventory

Previously a hierarchical clustering (HC) approach and a nearest neighbor (NN) approach were developed to model acute aquatic toxicity end points. These approaches were developed to correlate the toxicity for large, noncongeneric data sets. In this study these approaches applie...

How Much is Too Much? Toxic Chemicals in High School Labs.

ERIC Educational Resources Information Center

Nagel, Miriam C.

1982-01-01

Lists 37 chemicals classified as suspected carcinogens and suspected teratogens (chemicals capable of producing malformations in an embryo). Offers suggestions to high school chemistry teachers for conducting safe laboratory investigations by avoiding use of these potentially toxic materials. (Author/JN)

Toxic and carcinogenic agents in dry and moist snuff.

PubMed

Hoffmann, D; Adams, J D; Lisk, D; Fisenne, I; Brunnemann, K D

1987-12-01

The oral use of snuff is causatively associated with cancer of the oral cavity. Since most epidemiologic studies to date relate to the long-term use of dry snuff, which has dominated the U.S. smokeless tobacco market in the past, the concentrations of several toxic and carcinogenic agents in the three most popular dry snuff brands have been compared with those in the five most popular moist snuff brands sold in the United States. All eight samples were analyzed for nitrate, alkaloids, polyphenols, volatile carbonyl compounds, lead, cadmium, selenium, and the carcinogenic compounds benzo[a]pyrene (CAS: 50-32-8), polonium-210 (CAS: 13981-52-7), volatile N-nitrosamines (VNAs), N-nitrosodiethanolamine (CAS: 1116-54-7), and the tobacco-specific N-nitrosamines (TSNAs). Most of the snuff brands were rich in nitrate (greater than or equal to 1.5%), total polyphenols (greater than 2%), and in nicotine (greater than or equal to 1.5%), which is the habituating factor in tobacco use. Concentrations of the VNAs were significantly above the permissible limits set for some food products; the concentrations of the TSNAs in both snuff types exceeded the levels of nitrosamines in other consumer products by at least two to three orders of magnitude. The extremely high levels of the TSNAs in snuff have remained unchanged during the last decade and present the major carcinogenic risk factor for the oral use of snuff. Polonium-210 contributes further to the carcinogenic risk associated with snuff. The chemical-analytical data presented in this study do not indicate marked differences in the carcinogenic potential of moist snuff compared to dry snuff.

Aflatoxins--experimental studies.

PubMed

Tulpule, P G

1981-01-01

The susceptibility of animals to both chronic and acute aflatoxicosis is variable between species and depends upon not only the dose of the toxin and the duration of exposure but also upon the age, sex, and nutritional status of the animal. In general, acute toxicity is manifested by necrosis and cirrhosis, and chronic toxicity by carcinoma of the liver. Current research using both in vivo and in vitro studies has shown that the differences in response to aflatoxin in different animals can be attributed to their differential metabolism. The rates of metabolism and intermediate products formed are important factors in determining the type of toxic action of aflatoxin B1. According to these criteria, monkey and man are more susceptible to acute aflatoxicosis and relatively resistant to carcinogenic effects. On the other hand, animals, such as sheep and rat, are more susceptible to carcinogenic effects.

Effects of ascorbic acid on carcinogenicity and acute toxicity of nickel subsulfide, and on tumor transplants growth in gulonolactone oxidase knock-out mice and wild-type C57BL mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kasprzak, Kazimierz S.; Diwan, Bhalchandra A.; Kaczmarek, Monika Z.

2011-11-15

The aim of this study was to test a hypothesis that ascorbate depletion could enhance carcinogenicity and acute toxicity of nickel. Homozygous L-gulono- < gamma > -lactone oxidase gene knock-out mice (Gulo-/- mice) unable to produce ascorbate and wild-type C57BL mice (WT mice) were injected intramuscularly with carcinogenic nickel subsulfide (Ni{sub 3}S{sub 2}), and observed for the development of injection site tumors for 57 weeks. Small pieces of one of the induced tumors were transplanted subcutaneously into separate groups of Gulo-/- and WT mice and the growth of these tumors was measured for up to 3 months. The two strainsmore » of mice differed significantly with regard to (1) Ni{sub 3}S{sub 2} carcinogenesis: Gulo-/- mice were 40% more susceptible than WT mice; and (2) transplanted tumors development: Gulo-/- mice were more receptive to tumor growth than WT mice, but only in terms of a much shorter tumor latency; later in the exponential phase of growth, the growth rates were the same. And, with adequate ascorbate supplementation, the two strains were equally susceptible to acute toxicity of Ni{sub 3}S{sub 2}. Statistically significant effects of dietary ascorbate dosing levels were the following: (1) reduction in ascorbate supplementation increased acute toxicity of Ni{sub 3}S{sub 2} in Gulo-/- mice; (2) ascorbate supplementation extended the latency of transplanted tumors in WT mice. In conclusion, the lack of endogenous ascorbate synthesis makes Gulo-/- mice more susceptible to Ni{sub 3}S{sub 2} carcinogenesis. Dietary ascorbate tends to attenuate acute toxicity of Ni{sub 3}S{sub 2} and to extend the latency of transplanted tumors. The latter effects may be of practical importance to humans and thus deserve further studies. -- Highlights: Black-Right-Pointing-Pointer Ascorbate depletion enhances carcinogenicity and acute toxicity of nickel. Black-Right-Pointing-Pointer Gulo-/- mice unable to synthesize ascorbate were used in this study. Black-Right-Pointing-Pointer The reduction in ascorbate levels in Gulo-/- mice increased acute toxicity induced by Ni{sub 3}S{sub 2}. Black-Right-Pointing-Pointer Gulo-/- mice were found to be 40% more susceptible than WT mice to nickel-induced carcinogenesis.« less

Heavy Metals Toxicity and the Environment

PubMed Central

Tchounwou, Paul B; Yedjou, Clement G; Patlolla, Anita K; Sutton, Dwayne J

2013-01-01

Heavy metals are naturally occurring elements that have a high atomic weight and a density at least 5 times greater than that of water. Their multiple industrial, domestic, agricultural, medical and technological applications have led to their wide distribution in the environment; raising concerns over their potential effects on human health and the environment. Their toxicity depends on several factors including the dose, route of exposure, and chemical species, as well as the age, gender, genetics, and nutritional status of exposed individuals. Because of their high degree of toxicity, arsenic, cadmium, chromium, lead, and mercury rank among the priority metals that are of public health significance. These metallic elements are considered systemic toxicants that are known to induce multiple organ damage, even at lower levels of exposure. They are also classified as human carcinogens (known or probable) according to the U.S. Environmental Protection Agency, and the International Agency for Research on Cancer. This review provides an analysis of their environmental occurrence, production and use, potential for human exposure, and molecular mechanisms of toxicity, genotoxicity, and carcinogenicity. PMID:22945569

Reduction of aflatoxin B1 to aflatoxicol: a comprehensive DFT study provides clues to its toxicity.

PubMed

Karabulut, Sedat; Paytakov, Guvanchmyrat; Leszczynski, Jerzy

2014-12-01

Aflatoxicol (AFL) is one of most the important metabolites of aflatoxin B1 (AFB1). AFL can be formed through enzymatic or synthetic reduction of AFB1. Various experimental and theoretical studies have been focused on the AFB1 due to its high toxicity and carcinogenicity. The selective reduction of AFB1 carbonyls, molecular structure of AFL and its effect on toxicity has been studied here by the density functional theory (DFT) method. Although the toxicity of AFL is 18 times lower than that of AFB1, it has been concluded that both molecular structures have similar potency to form an exo-epoxide (AFEP) analogue which can bind to DNA. Calculations revealed that only one of the three possible tautomers of AFL is stable, both in the gas phase and water. The electronic properties of aflatoxicol are calculated as similar to aflatoxin B1 and this may be an explanation of similar carcinogenicity and toxicity of these compounds, which has been proved by experimental results. © 2014 Society of Chemical Industry.

Evaluation of the Inhalation Carcinogenicity of Ethylene Oxide ...

EPA Pesticide Factsheets

EPA has finalized its Evaluation of the Inhalation Carcinogenicity of Ethylene Oxide. This assessment addresses the potential carcinogenicity from long-term inhalation exposure to ethylene oxide. Now final, this assessment updates the carcinogenicity information in EPA’s 1985 Health Assessment Document. EPA’s program and regional offices may use this assessment to inform decisions to protect human health. The Toxicological Review and charge were reviewed internally by EPA and by other federal agencies and White House Offices before public release. Consistent with the May 2009 IRIS assessment development process, all written comments on IRIS assessments submitted by other federal agencies and White House Offices are made publicly available. Accordingly, interagency comments and the interagency science consultation materials provided to other agencies, including interagency review drafts of the IRIS Toxicological Review of Ammonia and the charge to external peer reviewers, are posted on this site.

Single Aflatoxin Contaminated Corn Kernel Analysis with Fluorescence Hyperspectral Image

USDA-ARS?s Scientific Manuscript database

Aflatoxins are toxic secondary metabolites of the fungi Aspergillus flavus and Aspergillus parasiticus, among others. Aflatoxin contaminated corn is toxic to domestic animals when ingested in feed and is a known carcinogen associated with liver and lung cancer in humans. Consequently, aflatoxin leve...

GENOTYPE AND PHENOTYPE IN THE METABOLISM, TOXICITY AND CARCINOGENICITY OF ARSENIC

EPA Science Inventory

This research will study the role of genetic factors in the expression of arsenic toxicity. The project will determine whether the interindividual variation in response is related to differences in the capacity to metabolize inorganic arsenic, if these differences in metabolic c...

Survey of toxicity and carcinogenity of mineral deposits

DOE Office of Scientific and Technical Information (OSTI.GOV)

Furst, A.; Harding-Barlow, I.

1981-11-03

The toxicities and biogeochemical cycles of arsenic, cadmium, chromium, lead and nickel are reviewed in some detail, and other trace elements briefly mentioned. These heavy metals are used as a framework within which the problem of low-level radioactive waste disposal can be compared. (ACR)

Best practices for clinical pathology testing in carcinogenicity studies.

PubMed

Young, Jamie K; Hall, Robert L; O'Brien, Peter; Strauss, Volker; Vahle, John L

2011-02-01

The Society of Toxicologic Pathology (STP) and American Society for Veterinary Clinical Pathology (ASCVP) convened a Clinical Pathology in Carcinogenicity Studies Working Group to recommend best practices for inclusion of clinical pathology testing in carcinogenicity studies. Regulatory guidance documents and literature were reviewed, and veterinary pathologists from North America, Japan, and Europe were surveyed regarding current practices, perceived value, and recommendations for clinical pathology testing in carcinogenicity studies. For two-year rodent carcinogenicity studies, the Working Group recommends that clinical pathology testing be limited to collection of blood smears at scheduled and unscheduled sacrifices to be examined only if indicated to aid in the diagnosis of possible hematopoietic neoplasia following histopathologic evaluation. Additional clinical pathology testing is most appropriately used to address specific issues from prior toxicity studies or known test article-related class effects. Inadequate data were available to make a recommendation concerning clinical pathology testing for alternative six-month carcinogenicity assays using genetically modified mice, although the Working Group suggests that it may be appropriate to use the same approach as for two-year carcinogenicity studies since the study goal is the same.

Zinc Chromate Induces Chromosome Instability and DNA Double Strand Breaks in Human Lung Cells

PubMed Central

Xie, Hong; Holmes, Amie L.; Young, Jamie L.; Qin, Qin; Joyce, Kellie; Pelsue, Stephen C.; Peng, Cheng; Wise, Sandra S.; Jeevarajan, Antony S.; Wallace, William T.; Hammond, Dianne; Wise, John Pierce

2014-01-01

Hexavalent chromium Cr(VI) is a respiratory toxicant and carcinogen, with solubility playing an important role in its carcinogenic potential. Zinc chromate, a water insoluble or ‘particulate’ Cr(VI) compound, has been shown to be carcinogenic in epidemiology studies and to induce tumors in experimental animals, but its genotoxicity is poorly understood. Our study shows that zinc chromate induced concentration-dependent increases in cytotoxicity, chromosome damage and DNA double strand breaks in human lung cells. In response to zinc chromate-induced breaks, MRE11 expression was increased and ATM and ATR were phosphorylated, indicating that the DNA double strand break repair system was initiated in the cells. In addition, our data show that zinc chromate-induced double strand breaks were only observed in the G2/M phase population, with no significant amount of double strand breaks observed in G1 and S phase cells. These data will aid in understanding the mechanisms of zinc chromate toxicity and carcinogenesis. PMID:19027772

Human Health Effects of Dichloromethane: Key Findings and Scientific Issues

PubMed Central

Schlosser, Paul M.; Bale, Ambuja S.; Gibbons, Catherine F.; Wilkins, Amina

2014-01-01

Background: The U.S. EPA’s Integrated Risk Information System (IRIS) completed an updated toxicological review of dichloromethane in November 2011. Objectives: In this commentary we summarize key results and issues of this review, including exposure sources, identification of potential health effects, and updated physiologically based pharmacokinetic (PBPK) modeling. Methods: We performed a comprehensive review of primary research studies and evaluation of PBPK models. Discussion: Hepatotoxicity was observed in oral and inhalation exposure studies in several studies in animals; neurological effects were also identified as a potential area of concern. Dichloromethane was classified as likely to be carcinogenic in humans based primarily on evidence of carcinogenicity at two sites (liver and lung) in male and female B6C3F1 mice (inhalation exposure) and at one site (liver) in male B6C3F1 mice (drinking-water exposure). Recent epidemiologic studies of dichloromethane (seven studies of hematopoietic cancers published since 2000) provide additional data raising concerns about associations with non-Hodgkin lymphoma and multiple myeloma. Although there are gaps in the database for dichloromethane genotoxicity (i.e., DNA adduct formation and gene mutations in target tissues in vivo), the positive DNA damage assays correlated with tissue and/or species availability of functional glutathione S-transferase (GST) metabolic activity, the key activation pathway for dichloromethane-induced cancer. Innovations in the IRIS assessment include estimation of cancer risk specifically for a presumed sensitive genotype (GST-theta-1+/+), and PBPK modeling accounting for human physiological distributions based on the expected distribution for all individuals 6 months to 80 years of age. Conclusion: The 2011 IRIS assessment of dichloromethane provides insights into the toxicity of a commonly used solvent. Citation: Schlosser PM, Bale AS, Gibbons CF, Wilkins A, Cooper GS. 2015. Human health effects of dichloromethane: key findings and scientific issues. Environ Health Perspect 123:114–119; http://dx.doi.org/10.1289/ehp.1308030 PMID:25325283

IRIS Toxicological Review of Dichlorobenzenes (2004 External Review Draft)

EPA Science Inventory

The goal of this assessment is to evaluate both carcinogenic and non-cancer toxicity based on the proposed July 1999 Cancer Guidelines and other relevant guidance. This approach will provide a better understanding of the toxicity and will aid in making informed risk-based decisio...

Proteomic Responses of BEAS-2B Cells to Nontoxic and Toxic Chromium: Protein Indicators of Cytotoxicity Conversion

EPA Science Inventory

Hexavalent chromium (Cr (VI)) is an environmental human carcinogen which primarily targets lungs. Among a variety of toxic mechanisms, disruption of biological pathways via translational and post-translational modifications represents a key mechanism through which Cr (VI) induces...

Safety assessment of GM plants: An updated review of the scientific literature.

PubMed

Domingo, José L

2016-09-01

In a wide revision of the literature conducted in 2000, I noted that the information in scientific journals on the safety of genetically modified (GM) foods in general, and GM plants in particular, was scarce. Of course, it was not sufficient to guarantee that the consumption of these products should not mean risks for the health of the consumers. Because of the scientific interest in GM organisms (GMOs), as well as the great concern that the consumption of GM foods/plants has raised in a number of countries, I conducted two subsequent revisions (2007 and 2011) on the adverse/toxic effects of GM plants. In the present review, I have updated the information on the potential adverse health effects of GM plants consumed as food and/or feed. With only a few exceptions, the reported studies in the last six years show rather similar conclusions; that is to say, the assessed GM soybeans, rice, corn/maize and wheat would be as safe as the parental species of these plants. However, in spite of the notable increase in the available information, studies on the long-term health effects of GM plants, including tests of mutagenicity, teratogenicity and carcinogenicity seem to be still clearly necessary. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hydroquinone: environmental pollution, toxicity, and microbial answers.

PubMed

Enguita, Francisco J; Leitão, Ana Lúcia

2013-01-01

Hydroquinone is a major benzene metabolite, which is a well-known haematotoxic and carcinogenic agent associated with malignancy in occupational environments. Human exposure to hydroquinone can occur by dietary, occupational, and environmental sources. In the environment, hydroquinone showed increased toxicity for aquatic organisms, being less harmful for bacteria and fungi. Recent pieces of evidence showed that hydroquinone is able to enhance carcinogenic risk by generating DNA damage and also to compromise the general immune responses which may contribute to the impaired triggering of the host immune reaction. Hydroquinone bioremediation from natural and contaminated sources can be achieved by the use of a diverse group of microorganisms, ranging from bacteria to fungi, which harbor very complex enzymatic systems able to metabolize hydroquinone either under aerobic or anaerobic conditions. Due to the recent research development on hydroquinone, this review underscores not only the mechanisms of hydroquinone biotransformation and the role of microorganisms and their enzymes in this process, but also its toxicity.

[Glyphosate--a non-toxic pesticide?].

PubMed

Pieniazek, Danuta; Bukowska, Bozena; Duda, Wirgiliusz

2003-01-01

Glyphosate is currently the most commonly applied herbicide and its use is still growing. Nowadays, over 50 commercial preparations containing this compound are used, and these formulations are much more toxic than their active compound, glyphosate, owing to the presence of many surfactants and carrier compounds. Toxicological investigations provide evidence that glyphosate is an extremely "safe" herbicide for animals. This is why its use in agriculture is universal. In June 1991, the Environmental Protection Agency (EPA) categorized this compound into class E (according to EPA there are five categories of carcinogenicity), which means that it is probably not carcinogenic to humans. Unfortunately, the study carried out by Swedish oncologists in 2001 showed that glyphosate may induce cancer of the lymphatic system. The results of the Swedish study have changed our opinion about "safety" of this herbicide. Investigations concerning both its accumulation and toxic effect in animals and plants are now under way in many laboratories.

Prediction of Chemical Carcinogenicity in Rodents from in vitro Genetic Toxicity Assays

NASA Astrophysics Data System (ADS)

Tennant, Raymond W.; Margolin, Barry H.; Shelby, Michael D.; Zeiger, Errol; Haseman, Joseph K.; Spalding, Judson; Caspary, William; Resnick, Michael; Stasiewicz, Stanley; Anderson, Beth; Minor, Robert

1987-05-01

Four widely used in vitro assays for genetic toxicity were evaluated for their ability to predict the carcinogenicity of selected chemicals in rodents. These assays were mutagenesis in Salmonella and mouse lymphoma cells and chromosome aberrations and sister chromatid exchanges in Chinese hamster ovary cells. Seventy-three chemicals recently tested in 2-year carcinogenicity studies conducted by the National Cancer Institute and the National Toxicology Program were used in this evaluation. Test results from the four in vitro assays did not show significant differences in individual concordance with the rodent carcinogenicity results; the concordance of each assay was approximately 60 percent. Within the limits of this study there was no evidence of complementarity among the four assays, and no battery of tests constructed from these assays improved substantially on the overall performance of the Salmonella assay. The in vitro assays which represented a range of three cell types and four end points did show substantial agreement among themselves, indicating that chemicals positive in one in vitro assay tended to be positive in the other in vitro assays. To help put this project into its proper context, we emphasize certain features of the study: 1) Standard protocols were used to mimic the major use of STTs worldwide--screening for mutagens and carcinogens; no attempt was made to optimize protocols for specific chemicals. 2) The 73 NTP chemicals and their 60% incidence of carcinogenicity are probably not representative of the universe of chemicals but rather reflect the recent chemical selection process for the NTP carcinogenicity assay. 3) The small, diverse group of chemicals precludes a meaningful evaluation of the predictive utility of chemical structure information. 4) The NTP is currently testing these same 73 chemicals in two in vivo STTs for chromosomal effects. 5) Complete data for an additional group of 30 to 40 NTP chemicals will be gathered on carcinogenicity and the four in vitro STTs to attempt to confirm the current findings. The standard against which the performance of STTs is measured has changed dramatically in the past decade. The high levels of concordance published in the early 1970s were accurate at the time. Nearly all known carcinogens tested were genotoxic, and there was little experimental evidence on which to base a judgment of noncarcinogenicity which, taken together, restricted assessment of test performances with noncarcinogens. With the increasing availability of results from NCI and NTP 2-year carcinogenicity studies in rodents, higher frequencies of nongenotoxic carcinogens and genotoxic noncarcinogens have been observed; this has resulted in the reduced concordance of the STT results with carcinogenicity results. It is clear that even with a battery of assays, not all rodent carcinogens are in vitro mutagens nor are all in vitro mutagens rodent carcinogens. If current in vitro STTs are expected to replace long-term rodent studies for the identification of chemical carcinogens, then that expectation should be abandoned. STTs do, however, continue to offer an economical, rapid, and dependable means to detect genotoxic chemicals. There is a range of applications in which STTs have been used successfully, from the identification of mutagenic fractions in complex mixtures such as cooked meat (32, 33) or air pollutants (34) to the early identification of genetic toxicity in the development of new chemical products (35). Requirements for the use of STT have not been consistent in both the national and international regulatory agencies. This is evident in the variety of testing requirements (8) and the different impacts that positive test results have on the registration or further testing requirements of chemicals. Consensus on these matters is not likely to occur in the near future, but agreement should be possible in certain areas. For instance, any time a new test or strategy is proposed, it is imperative that there be documentation by a substantial set of systematically acquired test results on well-defined rodent carcinogens and noncarcinogens (36). The current study represents a prototype of the evaluative effort needed for such documentation. Results of the current study focus attention on two questions involving discordances between carcinogenicity and genotoxicity test results: (i) Do nongenotoxic rodent carcinogens pose the same carcinogenic risk to humans as those that are genotoxic? (ii) Can the apparent high frequency of in vitro genotoxic rodent noncarcinogens be explained as a combination of artifacts arising from extremely high dosing in in vitro tests or the failure of many bona fide in vitro genotoxins to express their genetic toxicity in whole animals? Until these questions are resolved, chemicals that show mutagenic effects, particularly if such effects are observed in vivo, must be initially considered to pose human health risks as long as the somatic mutation theory of cancer remains a viable explanation for the etiology of some chemically induced cancers.

Health benefit from decreasing exposure to heavy metals and metalloid after strict pollution control measures near a typical river basin area in China.

PubMed

Cao, Suzhen; Duan, Xiaoli; Ma, Yingqun; Zhao, Xiuge; Qin, Yanwen; Liu, Yan; Li, Sai; Zheng, Binghui; Wei, Fusheng

2017-10-01

The metal(loid) pollution still is a great concern due to the effects from urbanization and industrialization. While, the health risks from the toxic metal(loid)s could decrease if strict pollution control measures were adopted. However, few studies to date investigate the health risks of heavy metal(loid)s in a systematic river basin for the dependent residents, after taking pollution control measures. Thus, the contents of metal(loid)s (Cu, Pb, Zn, Cd, Mn, As) in surface water along a typical river basin were investigated in this study, and the potential non-carcinogenic and carcinogenic health risks posed to the residents were assessed. Although the soluble contents of Cu, Pb, Zn and Cd exceeded the respective thresholds in two sites located downstream the mine area, they were greatly decreased in comparison with previous contamination levels, and the soluble concentrations of all the metal(loid)s were within the relevant thresholds in the sites far away from the mining area. Moreover, the closer to the mining area, the higher the pollution levels of metal(loid)s. The total hazard index for non-carcinogenic risks of metal(loid)s were basically lower than the threshold (1) for the local population. Whereas, although the content of metal(loid)s were low (such as As), they could pose relative higher non-carcinogenic health risks. The result illustrated that pollution levels, toxicity of the contaminants and exposure behavior patterns all could contribute to the potential detrimental health risks. Additionally, the non-carcinogenic and carcinogenic risks from ingestion exposure were ∼2-∼4 orders of magnitude higher than those from dermal contact. The total carcinogenic risks were basically lower than the maximum tolerable levels (1.0 × 10 -4 ), indicating carcinogenic risks from most areas of the river could also be accepted. Among different population groups, heavy metal(loid)s posed relative higher non-carcinogenic and carcinogenic risks to the children in 0-5 years old. Fortunately, the surface water in most area of this basin is safe in usage for the local population and the health risks were basically acceptable in case exposed to the target metal(loid)s, after the river basin was in the charge of strict pollution control measures. Copyright © 2017 Elsevier Ltd. All rights reserved.

Beryllium Metal II. A Review of the Available Toxicity Data

PubMed Central

Strupp, Christian

2011-01-01

Beryllium metal was classified in Europe collectively with beryllium compounds, e.g. soluble salts. Toxicological equivalence was assumed despite greatly differing physicochemical properties. Following introduction of the Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) regulation, beryllium metal was classified as individual substance and more investigational efforts to appropriately characterize beryllium metal as a specific substance apart from soluble beryllium compounds was required. A literature search on toxicity of beryllium metal was conducted, and the resulting literature compiled together with the results of a recently performed study package into a comprehensive data set. Testing performed under Organisation for Economic Co-Operation and Development guidelines and Good Laboratory Practice concluded that beryllium metal was neither a skin irritant, an eye irritant, a skin sensitizer nor evoked any clinical signs of acute oral toxicity; discrepancies between the current legal classification of beryllium metal in the European Union (EU) and the experimental results were identified. Furthermore, genotoxicity and carcinogenicity were discussed in the context of the literature data and the new experimental data. It was concluded that beryllium metal is unlikely to be a classical nonthreshold mutagen. Effects on DNA repair and morphological cell transformation were observed but need further investigation to evaluate their relevance in vivo. Animal carcinogenicity studies deliver evidence of carcinogenicity in the rat; however, lung overload may be a species-specific confounding factor in the existing studies, and studies in other species do not give convincing evidence of carcinogenicity. Epidemiology has been intensively discussed over the last years and has the problem that the studies base on the same US beryllium production population and do not distinguish between metal and soluble compounds. It is noted that the correlation between beryllium exposure and carcinogenicity, even including the soluble compounds, remains under discussion in the scientific community and active research is continuing. PMID:21196456

Ochratoxin A induces rat renal carcinogenicity with limited induction of oxidative stress responses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qi, Xiaozhe; Yu, Tao; Zhu, Liye

Ochratoxin A (OTA) has displayed nephrotoxicity and renal carcinogenicity in mammals, however, no clear mechanisms have been identified detailing the relationship between oxidative stress and these toxicities. This study was performed to clarify the relationship between oxidative stress and the renal carcinogenicity induced by OTA. Rats were treated with 70 or 210 μg/kg b.w. OTA for 4 or 13 weeks. In the rats administrated with OTA for 13 weeks, the kidney was damaged seriously. Cytoplasmic vacuolization was observed in the outer stripe of the outer medulla. Karyomegaly was prominent in the tubular epithelium. Kidney injury molecule-1 (Kim-1) was detected inmore » the outer stripe of the outer medulla in both low- and high-dose groups. OTA increased the mRNA levels of clusterin in rat kidneys. Interestingly, OTA did not significantly alter the oxidative stress level in rat liver and kidney. Yet, some indications related to proliferation and carcinogenicity were observed. A dose-related increase in proliferating cell nuclear antigen (PCNA) was observed at 4 weeks in both liver and kidney, but at 13 weeks, only in the kidney. OTA down-regulated reactive oxygen species (ROS) and up-regulated vimentin and lipocalin 2 in rat kidney at 13 weeks. The p53 gene was decreased in both liver and kidney at 13 weeks. These results suggest that OTA caused apparent kidney damage within 13 weeks but exerted limited effect on oxidative stress parameters. It implies that cell proliferation is the proposed mode of action for OTA-induced renal carcinogenicity. - Highlights: • We studied OTA toxicities in both the rat liver and kidney for 13 weeks. • OTA exerts limited effects on oxidative stress in the rat liver and kidney. • OTA induced renal carcinogenicity resulting from cell proliferation.« less

Health Risk Assessment Approach for 2,3,7,8-Tetrachlorodibenzo-P-Dioxin (Draft)

EPA Science Inventory

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is one of the most toxic and environmentally stable pollutants. In addition to various toxic effects, TCDD has been found to cause teratogenic, fetocidal, reproductive and carcinogenic effects in animals. In humans it adversely affects v...

TISSUE DISTRIBUTION OF ARSENIC SPECIES IN MICE CHRONICALLY EXPOSED TO METHYLARSONOUS ACID

EPA Science Inventory

The metabolism of inorganic arsenic (iAs) in humans yields toxic and carcinogenic methyl-As (MAs) and dimethyl-As (DMAs) intermediates. Methylarsonous acid (MAsIII) is the most acutely toxic species of characterized iAs metabolites. Here, we examined the concentrations of As spec...

Mode(s) of action of arsenic-induced tumors and toxicity.

EPA Science Inventory

Although arsenic has long been known for its toxicity and carcinogenicity, it is unknown exactly how these adverse health effects ocurr. Three of the biggest unresolved issues in arsenic exposures and adverse health effects are (a) what is (are) the mode of action (MOA)(s) of ar...

Hyperspectral image classification and development of fluorescence index for single corn kernels infected with Aspergillus flavus

USDA-ARS?s Scientific Manuscript database

Aflatoxins are toxic secondary metabolites predominantly produced by the fungi Aspergillus flavus and A. parasiticus. Aflatoxin contaminated corn is toxic to domestic animals when ingested in feed and is a known carcinogen associated with liver and lung cancer in humans. Consequently, aflatoxin leve...

Differences in how rice plants processes arsenic in their cells

USDA-ARS?s Scientific Manuscript database

Arsenic (As), a carcinogenic heavy metal, is a problem in some drinking water and staple food supplies around the world. Rice plants readily uptake arsenic and transport a portion of it into the grain. Arsenic is also toxic to plants; therefore mechanisms that reduce toxicity or accumulation have ev...

Covalent Binding of Aromatic Amines to Natural Organic Matter: Study of Reaction Mechanisms and Development of Remediation Schemes

EPA Science Inventory

Aromatic amines comprise an important class of environmental contaminants. Concern over their environmental fate arises from the toxic effects that certain aromatic amines exhibit toward microbial populations and reports that they can be toxic or carcinogenic to animals. Aromatic...

FACTORS MODULATING THE EPITHELIAL RESPONSE TO TOXICANTS IN TRACHEOBRONCHIAL AIRWAYS. (R827442)

EPA Science Inventory

As one of the principal interfaces between the organism and the environment, the respiratory system is a target for a wide variety of toxicants and carcinogens. The cellular and architectural complexity of the respiratory system appears to play a major role in defining the foc...

THE EXPANDING ROLE OF PREDICTIVE TOXICOLOGY: AN UPDATE ON THE (Q)SAR MODELS FOR MUTAGENS AND CARCINOGENS.

EPA Science Inventory

Different regulatory schemes worldwide, and in particular the preparation for the new REACH legislation in Europe, increase the reliance on estimation methods for predicting potential chemical hazard.

Role of Mutagenicity in Asbestos Fiber-Induced Carcinogenicity and Other Diseases

PubMed Central

Huang, Sarah X. L.; Jaurand, Marie-Claude; Kamp, David W.; Whysner, John; Hei, Tom K.

2011-01-01

The cellular and molecular mechanisms of how asbestos fibers induce cancers and other diseases are not well understood. Both serpentine and amphibole asbestos fibers have been shown to induce oxidative stress, inflammatory responses, cellular toxicity and tissue injuries, genetic changes, and epigenetic alterations in target cells in vitro and tissues in vivo. Most of these mechanisms are believe to be shared by both fiber-induced cancers and noncancerous diseases. This article summarizes the findings from existing literature with a focus on genetic changes, specifically, mutagenicity of asbestos fibers. Thus far, experimental evidence suggesting the involvement of mutagenesis in asbestos carcinogenicity is more convincing than asbestos-induced fibrotic diseases. The potential contributions of mutagenicity to asbestos-induced diseases, with an emphasis on carcinogenicity, are reviewed from five aspects: (1) whether there is a mutagenic mode of action (MOA) in fiber-induced carcinogenesis; (2) mutagenicity/carcinogenicity at low dose; (3) biological activities that contribute to mutagenicity and impact of target tissue/cell type; (4) health endpoints with or without mutagenicity as a key event; and finally, (5) determinant factors of toxicity in mutagenicity. At the end of this review, a consensus statement of what is known, what is believed to be factual but requires confirmation, and existing data gaps, as well as future research needs and directions, is provided. PMID:21534089

Cellular distribution of cell cycle-related molecules in the renal tubules of rats treated with renal carcinogens for 28 days: relationship between cell cycle aberration and carcinogenesis.

PubMed

Taniai, Eriko; Hayashi, Hitomi; Yafune, Atsunori; Watanabe, Maiko; Akane, Hirotoshi; Suzuki, Kazuhiko; Mitsumori, Kunitoshi; Shibutani, Makoto

2012-09-01

Some renal carcinogens can induce karyomegaly, which reflects aberrant cell division in the renal tubules, from the early stages of exposure. To clarify the cell cycle-related changes during the early stages of renal carcinogenesis, we performed immunohistochemical analysis of tubular cells in male F344 rats treated with carcinogenic doses of representative renal carcinogens for 28 days. For this purpose, the karyomegaly-inducing carcinogens ochratoxin A (OTA), ferric nitrilotriacetic acid, and monuron, and the non-karyomegaly-inducing carcinogens tris(2-chloroethyl) phosphate and potassium bromate were examined. For comparison, a karyomegaly-inducing non-carcinogen, p-nitrobenzoic acid, and a non-carcinogenic non-karyomegaly-inducing renal toxicant, acetaminophen, were also examined. The outer stripe of the outer medulla (OSOM) and the cortex + OSOM were subjected to morphometric analysis of immunoreactive proximal tubular cells. Renal carcinogens, irrespective of their karyomegaly-inducing potential, increased proximal tubular cell proliferation accompanied by an increase in topoisomerase IIα-immunoreactive cells, suggesting a reflection of cell proliferation. Karyomegaly-inducing carcinogens increased nuclear Cdc2-, γH2AX-, and phosphorylated Chk2-immunoreactive cells in both areas, the former two acting in response to DNA damage and the latter one suggestive of sustained G₂. OTA, an OSOM-targeting carcinogen, could easily be distinguished from untreated controls and non-carcinogens by evaluation of molecules responding to DNA damage and G₂/M transition in the OSOM. Thus, all renal carcinogens examined facilitated proximal tubular proliferation by repeated short-term treatment. Among these, karyomegaly-inducing carcinogens may cause DNA damage and G₂ arrest in the target tubular cells.

Levels of selected carcinogens and toxicants in vapour from electronic cigarettes.

PubMed

Goniewicz, Maciej Lukasz; Knysak, Jakub; Gawron, Michal; Kosmider, Leon; Sobczak, Andrzej; Kurek, Jolanta; Prokopowicz, Adam; Jablonska-Czapla, Magdalena; Rosik-Dulewska, Czeslawa; Havel, Christopher; Jacob, Peyton; Benowitz, Neal

2014-03-01

Electronic cigarettes, also known as e-cigarettes, are devices designed to imitate regular cigarettes and deliver nicotine via inhalation without combusting tobacco. They are purported to deliver nicotine without other toxicants and to be a safer alternative to regular cigarettes. However, little toxicity testing has been performed to evaluate the chemical nature of vapour generated from e-cigarettes. The aim of this study was to screen e-cigarette vapours for content of four groups of potentially toxic and carcinogenic compounds: carbonyls, volatile organic compounds, nitrosamines and heavy metals. Vapours were generated from 12 brands of e-cigarettes and the reference product, the medicinal nicotine inhaler, in controlled conditions using a modified smoking machine. The selected toxic compounds were extracted from vapours into a solid or liquid phase and analysed with chromatographic and spectroscopy methods. We found that the e-cigarette vapours contained some toxic substances. The levels of the toxicants were 9-450 times lower than in cigarette smoke and were, in many cases, comparable with trace amounts found in the reference product. Our findings are consistent with the idea that substituting tobacco cigarettes with e-cigarettes may substantially reduce exposure to selected tobacco-specific toxicants. E-cigarettes as a harm reduction strategy among smokers unwilling to quit, warrants further study. (To view this abstract in Polish and German, please see the supplementary files online.).

A Tox21 Approach to Altered Epigenetic Landscapes: Assessing Epigenetic Toxicity Pathways Leading to Altered Gene Expression and Oncogenic Transformation In Vitro

PubMed Central

Parfett, Craig L.; Desaulniers, Daniel

2017-01-01

An emerging vision for toxicity testing in the 21st century foresees in vitro assays assuming the leading role in testing for chemical hazards, including testing for carcinogenicity. Toxicity will be determined by monitoring key steps in functionally validated molecular pathways, using tests designed to reveal chemically-induced perturbations that lead to adverse phenotypic endpoints in cultured human cells. Risk assessments would subsequently be derived from the causal in vitro endpoints and concentration vs. effect data extrapolated to human in vivo concentrations. Much direct experimental evidence now shows that disruption of epigenetic processes by chemicals is a carcinogenic mode of action that leads to altered gene functions playing causal roles in cancer initiation and progression. In assessing chemical safety, it would therefore be advantageous to consider an emerging class of carcinogens, the epigenotoxicants, with the ability to change chromatin and/or DNA marks by direct or indirect effects on the activities of enzymes (writers, erasers/editors, remodelers and readers) that convey the epigenetic information. Evidence is reviewed supporting a strategy for in vitro hazard identification of carcinogens that induce toxicity through disturbance of functional epigenetic pathways in human somatic cells, leading to inactivated tumour suppressor genes and carcinogenesis. In the context of human cell transformation models, these in vitro pathway measurements ensure high biological relevance to the apical endpoint of cancer. Four causal mechanisms participating in pathways to persistent epigenetic gene silencing were considered: covalent histone modification, nucleosome remodeling, non-coding RNA interaction and DNA methylation. Within these four interacting mechanisms, 25 epigenetic toxicity pathway components (SET1, MLL1, KDM5, G9A, SUV39H1, SETDB1, EZH2, JMJD3, CBX7, CBX8, BMI, SUZ12, HP1, MPP8, DNMT1, DNMT3A, DNMT3B, TET1, MeCP2, SETDB2, BAZ2A, UHRF1, CTCF, HOTAIR and ANRIL) were found to have experimental evidence showing that functional perturbations played “driver” roles in human cellular transformation. Measurement of epigenotoxicants presents challenges for short-term carcinogenicity testing, especially in the high-throughput modes emphasized in the Tox21 chemicals testing approach. There is need to develop and validate in vitro tests to detect both, locus-specific, and genome-wide, epigenetic alterations with causal links to oncogenic cellular phenotypes. Some recent examples of cell-based high throughput chemical screening assays are presented that have been applied or have shown potential for application to epigenetic endpoints. PMID:28587163

Production of thymine glycols in DNA by radiation and chemical carcinogens as detected by a monoclonal antibody.

PubMed Central

Leadon, S. A.

1987-01-01

In order to understand the role in carcinogenesis of damage indirectly induced by chemical carcinogens, it is important to identify the primary DNA lesions. We have measured the formation and repair of one type of DNA modification, 5,6-dihydroxydihydrothymine (thymine glycol), following exposure of cultured human cells to the carcinogens N-hydroxy-2-naphthylamine or benzo(a)pyrene. The efficiency of production of thymine glycols in DNA by these carcinogens was compared to that by ionizing radiation and ultraviolet light. Thymine glycols were detected using a monoclonal antibody against this product in a sensitive immunoassay. We found that thymine glycols were produced in DNA in a dose dependent manner after exposure to the carcinogens and that their production was reduced if either catalase or superoxide dismutase or both were present at the time of treatment. The efficiency of thymine glycol production following exposure to the chemical carcinogens was greater than that following equi-toxic doses of radiation. Thymine glycols were efficiently removed from the DNA of human cells following treatment with either the chemical carcinogens, ionizing radiation or ultraviolet light. PMID:3477281

Nicotine yesterday, today, and tomorrow: a global review.

PubMed

Gray, Nigel J

2014-02-01

This intentionally selective global review reflects the views and frustrations of a public health physician with 45 years of frontline experience in tobacco control. In particular, it focuses on the nexus between research and policy and the long periods between relevant discoveries and application as policy. Consideration is given to the relative neglect of the possibility of reducing the carcinogenicity and toxicity of the cigarette on the grounds that it is the preferred source of nicotine for the global majority of nicotine users. Although the outcome of such change is unquantifiable, there is much in cigarette smoke that can be changed to make it less carcinogenic and less toxic. It is difficult to think of excuses for accepting the status quo.

Less-Toxic Coatings for Inhibiting Corrosion of Aluminum

NASA Technical Reports Server (NTRS)

Minevski, Zoran; Clarke, Eric; Eylem, Cahit; Maxey, Jason; Nelson, Carl

2003-01-01

Two recently invented families of conversion- coating processes have been found to be effective in reducing or preventing corrosion of aluminum alloys. These processes offer less-toxic alternatives to prior conversion-coating processes that are highly effective but have fallen out of favor because they generate chromate wastes, which are toxic and carcinogenic. Specimens subjected to these processes were found to perform well in standard salt-fog corrosion tests.

Epidemiological approaches in the investigation of environmental causes of cancer: the case of dioxins and water disinfection by-products

PubMed Central

2011-01-01

I will refer in this paper to difficulties in research in environmental causes of cancer using as examples research on dioxins and on drinking water disinfection by-products (DBPs) that have created considerable controversy in the scientific and wider community. Dioxins are highly toxic chemicals that are animal carcinogens. For many years, evaluation of the carcinogenicity of dioxins in humans was based on case-control or registry based studies. The development of methods to measure dioxins in blood indicated that these studies suffered from extreme exposure misclassification. The conduct of large cohort studies of workers with widely contrasted exposures together with the use of biomarkers and models for exposure assessment, led to convincing evidence on the carcinogenicity of dioxins in humans. The high toxicity of a few dioxin congeners, the availability of a scheme to characterize the toxicity of a mixture of dioxins and related compounds and the long half-life of these compounds facilitated epidemiological research. Contrary to dioxins, trihalomethanes (THMs) and most of the hundreds of DBPs in drinking water are chemicals of low toxicity. For more than 15 years, the main evidence on the carcinogenicity of DBPs was through ecological or death certificate studies. More recent studies based on individual assessment confirmed increases in bladder cancer risk. However even those studies ignored the toxicological evidence on the importance of routes of exposure to DBPs other than ingestion and, probably, underestimated the risk. Persistence of weak study designs together with delays in advanced exposure assessment models led to delays in confirming early evidence on the carcinogenicity of DBPs. The evaluation of only a few chemicals when exposure is to a complex mixture remains a major problem in exposure assessment for DBPs. The success of epidemiological studies in identifying increased risks lies primarily on the wide contrast of exposure to DBPs in the general population that overcomes the significant exposure misclassification. Exposure assessment has been the Achilles heel for studies on dioxins and DBPs and cancer. The combination of powerful study designs, advanced exposure assessment together with a better understanding of mechanisms of disease and the use of biomarkers of exposure, led to the strengthening of the epidemiological evidence. PMID:21489213

TISSUE DISTRIBUTION OF ARSENIC SPECIES IN MICE CHRONICALLY EXPOSED TO ARSENITE OR METHYLARSONOUS ACID

EPA Science Inventory

e metabolism of inorganic arsenic (iAs) in humans yields toxic and carcinogenic methyl-As (MAs) and dimethyl-As (DMAs) intermediates. Methylarsonous acid (MAsIII) is the most acutely toxic species among known iAs metabolites. In this study, we examined the concentrations of As sp...

75 FR 22234 - Phosphate Ester, Tallowamine, Ethoxylated; Exemption from the Requirement of a Tolerance

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-28

.../Developmental Toxicity Screening Test, clinical signs of toxicity (abnormal respiratory sounds, dyspnea... the AAPs are carcinogenic. The Agency used a qualitative structure activity relationship (QSAR... = 10x MOE = 300 in rats (MRID FQPA SF = 3x 47600707) (10% Dermal absorption; LOAEL = 200 mg/kg/day 100...

QUANTITATIVE TOXICOPROTEOMIC ANALYSIS OF CARCINOGEN-TREATED ANIMAL TISSUES AND HUMAN CELLS FOR HUMAN HEALTH RISK ASSESSMENT

EPA Science Inventory

Humans are exposed to a variety of environmental toxicants, and this together with a large number of interacting factors can contribute to an individual's risk for health. To understand the toxic mechanisms and/or modes of action for human health risk assessment, molecular charac...

Introduction to Toxicity and Risk Assessment for Project Chemists

DTIC Science & Technology

2012-03-27

Toxicity of Hexavalent Chromium  External review complete  EPA will wait until studies underway on carcinogenic mode of action are complete to...finalize the assessment  NJ and Cal values for hex chrome 16 Risk-Based Screening Levels Resident Soil (mg/kg) Resident Water Use (µg/L) DRAFT 0.04

Risk of human health by particulate matter as a source of air pollution--comparison with tobacco smoking.

PubMed

Enomoto, Makoto; Tierney, William J; Nozaki, Kohsuke

2008-08-01

Increased air pollution, containing carcinogenic particulate matter smaller than 2.5 microm (PM(2.5)), has gained particular attention in recent years as a causative factor in the increased incidence of respiratory diseases, including lung cancer. Extensive carcinogenicity studies conducted recently under Good Laboratory Practice conditions by National Toxicology Program in the USA, Ramazzini Foundation in Italy or Contract Research Organizations on numerous chemical compounds have demonstrated the importance of considering dose levels, times and duration of exposure in the safety evaluation of carcinogenic as well as classical toxic agents. Data on exposure levels to chemical carcinogens that produce tumor development have contributed to the evaluation of human carcinogens from extrapolation of animal data. A popular held misconception is that the risk from smoking is the result of inhaling assorted particulate matter and by products from burning tobacco rather than the very low ng levels of carcinogens present in smoke. Consider the fact that a piece of toasted bread contains ng levels of the carcinogen urethane (ethyl carbamate). Yet, no one has considered toast to be a human carcinogen. Future human carcinogenic risk assessment should emphasize consideration of inhalation exposure to higher levels of benzo (a) pyrene and other possible carcinogens and particulate matter present in polluted air derived from automobile exhaust, pitch and coal tar on paved roads and asbestos, in addition to other environmental contaminant exposure via the food and drinking water.

Polycyclic aromatic hydrocarbons in some grounded coffee brands.

PubMed

Grover, Inderpreet Singh; Sharma, Rashmi; Singh, Satnam; Pal, Bonamali

2013-08-01

Potentially toxic 16 priority polycyclic aromatic hydrocarbons (PAHs) were determined in four brands of grounded coffee. Four to 13 PAHs were detected. Concentrations of total PAHs in different brands of coffee samples were in the range of 831.7-1,589.7 μg/kg. Benzo[a]pyrene (2A: probable human carcinogen) was found in Nescafe Premium whereas naphthalene (2B: possible human carcinogen) was found in all the samples of coffee.

Update on the National Acrylamide Project

USDA-ARS?s Scientific Manuscript database

Acrylamide, a suspected human carcinogen that may delay fetal development, is a Maillard reaction product that forms when carbohydrate-rich foods are cooked at high temperatures. Processed potato products, including French fries and potato chips, make a substantial contribution to total dietary acry...

Aberrant activation of M phase proteins by cell proliferation-evoking carcinogens after 28-day administration in rats.

PubMed

Yafune, Atsunori; Taniai, Eriko; Morita, Reiko; Hayashi, Hitomi; Suzuki, Kazuhiko; Mitsumori, Kunitoshi; Shibutani, Makoto

2013-06-07

We have previously reported that hepatocarcinogens increase liver cells expressing p21(Cip1), a G1 checkpoint protein and M phase proteins after 28-day treatment in rats. This study aimed to identify early prediction markers of carcinogens available in many target organs after 28-day treatment in rats. Immunohistochemical analysis was performed on Ki-67, p21(Cip1) and M phase proteins [nuclear Cdc2, phospho-Histone H3 (p-Histone H3), Aurora B and heterochromatin protein 1α (HP1α)] with carcinogens targeting different organs. Carcinogens targeting thyroid (sulfadimethoxine; SDM), urinary bladder (phenylethyl isothiocyanate), forestomach (butylated hydroxyanisole; BHA), glandular stomach (catechol; CC), and colon (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and chenodeoxycholic acid) were examined using a non-carcinogenic toxicant (caprolactam) and carcinogens targeting other organs as negative controls. All carcinogens increased Ki-67(+), nuclear Cdc2(+), p-Histone H3(+) or Aurora B(+) carcinogenic target cells, except for both colon carcinogens, which did not increase cell proliferation. On the other hand, p21(Cip1+) cells increased with SDM and CC. HP1α responded only to BHA. Results revealed carcinogens evoking cell proliferation concurrently induced cell cycle arrest at M phase or showing chromosomal instability reflecting aberration in cell cycle regulation, irrespective of target organs, after 28-day treatment. Therefore, M phase proteins may be early prediction markers of carcinogens evoking cell proliferation in many target organs. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Mycotoxins as human carcinogens-the IARC Monographs classification.

PubMed

Ostry, Vladimir; Malir, Frantisek; Toman, Jakub; Grosse, Yann

2017-02-01

Humans are constantly exposed to mycotoxins (e.g. aflatoxins, ochratoxins), mainly via food intake of plant and animal origin. The health risks stemming from mycotoxins may result from their toxicity, in particular their carcinogenicity. In order to prevent these risks, the International Agency for Research on Cancer (IARC) in Lyon (France)-through its IARC Monographs programme-has performed the carcinogenic hazard assessment of some mycotoxins in humans, on the basis of epidemiological data, studies of cancer in experimental animals and mechanistic studies. The present article summarizes the carcinogenic hazard assessments of those mycotoxins, especially aflatoxins (aflatoxin B 1 , B 2 , G 1 , G 2 and M 1 ), fumonisins (fumonisin B 1 and B 2 ) and ochratoxin A (OTA). New information regarding the genotoxicity of OTA (formation of OTA-DNA adducts), the role of OTA in oxidative stress and the identification of epigenetic factors involved in OTA carcinogenesis-should they indeed provide strong evidence that OTA carcinogenicity is mediated by a mechanism that also operates in humans-could lead to the reclassification of OTA.

Risk assessment for carcinogens under California's Proposition 65

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pease, W.S.; Zeise, L.; Kelter, A.

1990-06-01

Risk assessments for carcinogens are being developed through an accelerated process in California as a part of the state's implementation of Proposition 65, the Safe Drinking Water and Toxic Enforcement Act. Estimates of carcinogenic potency made by the California Department of Health Services (CDHS) are generally similar to estimates made by the U.S. Environmental Protection Agency (EPA). The largest differences are due to EPA's use of the maximum likelihood estimate instead of CDHS' use of the upper 95% confidence bounds on potencies derived from human data and to procedures used to correct for studies of short duration or with earlymore » mortality. Numerical limits derived from these potency estimates constitute no significant risk levels, which govern exemption from Proposition 65's discharge prohibition and warning requirements. Under Proposition 65 regulations, lifetime cancer risks less than 10(-5) are not significant and cumulative intake is not considered. Following these regulations, numerical limits for a number of Proposition 65 carcinogens that are applicable to the control of toxic discharges are less stringent than limits under existing federal water pollution control laws. Thus, existing federal limits will become the Proposition 65 levels for discharge. Chemicals currently not covered by federal and state controls will eventually be subject to discharge limitations under Proposition 65. No significant risk levels (expressed in terms of daily intake of carcinogens) also trigger warning requirements under Proposition 65 that are more extensive than existing state or federal requirements. A variety of chemical exposures from multiple sources are identified that exceed Proposition 65's no significant risk levels.« less

Utilization of charge-transfer complexation for the detection of carcinogenic substances in foods: Spectroscopic characterization of ethyl carbamate with some traditional π-acceptors

NASA Astrophysics Data System (ADS)

Adam, Abdel Majid A.; Refat, Moamen S.; Saad, Hosam A.

2013-04-01

The study of toxic and carcinogenic substances in foods represents one of the most demanding areas in food safety, due to their repercussions for public health. One potentially toxic compound for humans is ethyl carbamate (EC). EC is a multi-site genotoxic carcinogen of widespread occurrence in fermented foods and alcoholic beverages. Structural and thermal stability of charge-transfer complexes formed between EC as a donor with quinol (QL), picric acid (PA), chloranilic acid (CLA), p-chloranil (p-CHL) and 1,3-dinitrobenzene (DNB) as acceptors were reported. Elemental analysis (CHN), electronic absorption spectra, photometric titration, IR, and 1H NMR spectra show that the interaction between EC and acceptors was stabilized by hydrogen bonding, via a 1:1 stoichiometry. Thermogravimetric (TG) analysis indicates that the formation of molecular CT complexes was stable, exothermic and spontaneous. Finally, the CT complexes were screened for their antibacterial and antifungal activities. The results indicated that the [(EC)(QL)] complex exhibited strong antimicrobial activities against various bacterial and fungal strains compared with standard drugs.

Updated Histologic Classification of Adenomas and Carcinomas in the Colon of Carcinogen-treated Sprague-Dawley Rats.

PubMed

Rubio, Carlos A

2017-12-01

Recent studies have disclosed novel histological phenotypes of colon tumours in carcinogen-treated rats. The aim of this study was to update the current histological classification of colonic neoplasias in Sprague-Dawley (SD) rats. Archival sections from 398 SD rats having 408 neoplasias in previous experiments were re-evaluated. Of the 408 colonic neoplasias, 11% (44/408) were adenomas without invasive growth and 89% (364/408) invasive carcinomas. Out of the 44 adenomas, 82% were conventional (tubular or villous), 14% traditional serrated (TSA; with unlocked serrations or with closed microtubules) and 5% gut-associated lymphoid tissue (GALT)-associated adenomas. Out of 364 carcinomas, 57% were conventional carcinomas, 26% GALT carcinomas, 8% undifferentiated, 6% signet-ring cell carcinomas, and 4% traditional serrated carcinomas (TSC). Thus, conventional adenomas, conventional carcinomas and GALT-associated carcinomas predominated (p<0.05). The updated classification of colonic tumours in SD rats includes conventional adenomas, TSA, GALT-associated adenomas, conventional carcinomas, TSC, GALT-associated carcinomas, signet-ring cell carcinomas and undifferentiated carcinomas. Several of the histological phenotypes reported here are not included in any of the current classifications of colonic tumours in rodents. This updated classification fulfils the requirements for an animal model of human disease, inasmuch as similar histological phenotypes of colon neoplasias have been documented in humans. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

The effects of environmental chemical carcinogens on the microRNA machinery.

PubMed

Izzotti, A; Pulliero, A

2014-07-01

The first evidence that microRNA expression is early altered by exposure to environmental chemical carcinogens in still healthy organisms was obtained for cigarette smoke. To date, the cumulative experimental data indicate that similar effects are caused by a variety of environmental carcinogens, including polycyclic aromatic hydrocarbons, nitropyrenes, endocrine disruptors, airborne mixtures, carcinogens in food and water, and carcinogenic drugs. Accordingly, the alteration of miRNA expression is a general mechanism that plays an important pathogenic role in linking exposure to environmental toxic agents with their pathological consequences, mainly including cancer development. This review summarizes the existing experimental evidence concerning the effects of chemical carcinogens on the microRNA machinery. For each carcinogen, the specific microRNA alteration signature, as detected in experimental studies, is reported. These data are useful for applying microRNA alterations as early biomarkers of biological effects in healthy organisms exposed to environmental carcinogens. However, microRNA alteration results in carcinogenesis only if accompanied by other molecular damages. As an example, microRNAs altered by chemical carcinogens often inhibits the expression of mutated oncogenes. The long-term exposure to chemical carcinogens causes irreversible suppression of microRNA expression thus allowing the transduction into proteins of mutated oncogenes. This review also analyzes the existing knowledge regarding the mechanisms by which environmental carcinogens alter microRNA expression. The underlying molecular mechanism involves p53-microRNA interconnection, microRNA adduct formation, and alterations of Dicer function. On the whole, reported findings provide evidence that microRNA analysis is a molecular toxicology tool that can elucidate the pathogenic mechanisms activated by environmental carcinogens. Copyright © 2014 Elsevier GmbH. All rights reserved.

Toxic substances alert program

NASA Technical Reports Server (NTRS)

Junod, T. L.

1978-01-01

A toxicity profile is provided, of 187 toxic substances procured by NASA Lewis Research Center during a 3 1/2 year period, including 27 known or suspected carcinogens. The goal of the program is to assure that the center's health and safety personnel are aware of the procurement and use of toxic substances and to alert and inform the users of these materials as to the toxic characteristics and the control measures needed to ensure their safe use. The program also provides a continuing record of the toxic substances procured, who procured them, what other toxic substances the user has obtained in the past, and where similar materials have been used elsewhere at the center.

Solubility of chrysotile asbestos and basalt fibers in relation to their fibrogenic and carcinogenic action.

PubMed

Kogan, F M; Nikitina, O V

1994-10-01

Fiber length and persistence are thought to be determinants for the development of toxic, fibrogenic, and carcinogenic effects of fibrous dusts. When the solubilities of chrysotile asbestos (CA) and basalt fibers (BF) were compared by measuring the loss of silica and magnesium in Leineweber's solution, CA was shown to be the more soluble. In a 6-month inhalation experiment, chrysotile at a mean concentration of 25 mg/m3 had a higher clearance rate than other comparable dusts. In acute toxicity studies, chrysotile and basalt fibers were administered intraperitoneally. At a dose of 1.7 g/kg body weight of CA, one third of the animals died. A dose of 2.7 g/kg body weight killed all the animals. With BF, even at a dose of 10 g/kg body weight all the animals survived. When the two fibers were administered over a 6-month period, either intratracheally or by inhalation, fibrotic lesions were more common in the group that received CA. Intraperitoneal administration of CA led to three times as many deaths from peritoneal mesothelioma as administration of BF. It appears, therefore, that in spite of its higher solubility and lower persistence, CA was the more toxic, fibrogenic and carcinogenic fiber, which gives rise to the hypothesis that the surface chemistry of the fibers is the determinant for biological activity.

Solubility of chrysotile asbestos and basalt fibers in relation to their fibrogenic and carcinogenic action.

PubMed Central

Kogan, F M; Nikitina, O V

1994-01-01

Fiber length and persistence are thought to be determinants for the development of toxic, fibrogenic, and carcinogenic effects of fibrous dusts. When the solubilities of chrysotile asbestos (CA) and basalt fibers (BF) were compared by measuring the loss of silica and magnesium in Leineweber's solution, CA was shown to be the more soluble. In a 6-month inhalation experiment, chrysotile at a mean concentration of 25 mg/m3 had a higher clearance rate than other comparable dusts. In acute toxicity studies, chrysotile and basalt fibers were administered intraperitoneally. At a dose of 1.7 g/kg body weight of CA, one third of the animals died. A dose of 2.7 g/kg body weight killed all the animals. With BF, even at a dose of 10 g/kg body weight all the animals survived. When the two fibers were administered over a 6-month period, either intratracheally or by inhalation, fibrotic lesions were more common in the group that received CA. Intraperitoneal administration of CA led to three times as many deaths from peritoneal mesothelioma as administration of BF. It appears, therefore, that in spite of its higher solubility and lower persistence, CA was the more toxic, fibrogenic and carcinogenic fiber, which gives rise to the hypothesis that the surface chemistry of the fibers is the determinant for biological activity. PMID:7882932

Comparison of essential and toxic elements in esophagus, lung, mouth and urinary bladder male cancer patients with related to controls.

PubMed

Kazi, Tasneem Gul; Wadhwa, Sham Kumar; Afridi, Hassan Imran; Talpur, Farah Naz; Tuzen, Mustafa; Baig, Jameel Ahmed

2015-05-01

There is a compelling evidence in support of negative associations between essential trace and toxic elements in different types of cancer. The aim of the present study was to investigate the relationship between carcinogenic (As, Cd, Ni) and anti-carcinogenic (Se, Zn) trace elements in scalp hair samples of different male cancerous patients (esophagus, lung, mouth, and urinary bladder). For comparative purposes, the scalp hair samples of healthy males of the same age group (ranged 35-65 years) as controls were analyzed. Both controls and patients have the same socioeconomic status, localities, dietary habits, and smoking locally made cigarette. The scalp hair samples were oxidized by 65% nitric acid: 30% hydrogen peroxide (2:1) ratio in microwave oven followed by atomic absorption spectrometry. The validity and accuracy of the methodology were checked using certified reference material of human hair BCR 397. The mean concentrations of As, Cd, and Ni were found to be significantly higher in scalp hair samples of patients having different cancers as compared to the controls, while reverse results were obtained in the case of Se and Zn levels (p < 0.01). The study revealed that the carcinogenic processes are significantly affecting the trace elements burden and mutual interaction of essential trace and toxic elements in the cancerous patients.

Chronic toxicity and carcinogenicity studies of chromium picolinate monohydrate administered in feed to F344/N rats and B6C3F1 mice for 2 years.

PubMed

Stout, M D; Nyska, A; Collins, B J; Witt, K L; Kissling, G E; Malarkey, D E; Hooth, M J

2009-04-01

Trivalent chromium (Cr(III)) has been proposed to be an essential element, which may increase sensitivity to insulin and thus participate in carbohydrate and lipid metabolism. Humans ingest Cr(III) both as a natural dietary constituent and in dietary supplements taken for weight loss and antidiabetic effects. Chromium picolinate (CP), a widely used supplement, contains Cr(III) chelated with three molecules of picolinic acid and was formulated in an attempt to improve the absorption of Cr(III). In order to examine the potential for CP to induce chronic toxicity and carcinogenicity, the NTP conducted studies of the monohydrate form (CPM) in groups of 50 male and female F344/N rats and B6C3F1 mice exposed in feed to concentrations of 0, 2000, 10,000 or 50,000 ppm for 2 years; exposure concentrations were selected following review of the data from NTP 3-month toxicity studies. Exposure to CPM did not induce biologically significant changes in survival, body weight, feed consumption, or non-neoplastic lesions in rats or mice. In male rats, a statistically significant increase in the incidence of preputial gland adenoma at 10,000 ppm was considered an equivocal finding. CPM was not carcinogenic to female rats or to male or female mice.

Chronic Toxicity and Carcinogenicity Studies of Chromium Picolinate Monohydrate Administered in Feed to F344/N Rats and B6C3F1 Mice for 2 Years

PubMed Central

Stout, M.D.; Nyska, A.; Collins, B.J.; Witt, K.L.; Kissling, G.E.; Malarkey, D.E.; Hooth, M.J.

2009-01-01

Trivalent chromium (Cr(III)) has been proposed to be an essential element, which may increase sensitivity to insulin and thus participate in carbohydrate and lipid metabolism. Humans ingest Cr(III) both as a natural dietary constituent and in dietary supplements taken for weight loss and antidiabetic effects. Chromium picolinate (CP), a widely used supplement, contains Cr(III) chelated with three molecules of picolinic acid and was formulated in an attempt to improve the absorption of Cr(III). In order to examine the potential for CP to induce chronic toxicity and carcinogenicity, the NTP conducted studies of the monohydrate form (CPM) in groups of 50 male and female F344/N rats and B6C3F1 mice exposed in feed to concentrations of 0, 2,000, 10,000 or 50,000 ppm for 2 years; exposure concentrations were selected following review of the data from NTP 3-month toxicity studies. Exposure to CPM did not induce biologically significant changes in survival, body weight, feed consumption, or non-neoplastic lesions in rats or mice. In male rats, a statistically significant increase in the incidence of preputial gland adenoma at 10,000 ppm was considered an equivocal finding. CPM was not carcinogenic to female rats or to male or female mice. PMID:19166900

A Novel Approach: Chemical Relational Databases, and the ...

EPA Pesticide Factsheets

Mutagenicity and carcinogenicity databases are crucial resources for toxicologists and regulators involved in chemicals risk assessment. Until recently, existing public toxicity databases have been constructed primarily as

Evaluation of the sensitivity and specificity of in vivo erythrocyte micronucleus and transgenic rodent gene mutation tests to detect rodent carcinogens.

PubMed

Morita, Takeshi; Hamada, Shuichi; Masumura, Kenichi; Wakata, Akihiro; Maniwa, Jiro; Takasawa, Hironao; Yasunaga, Katsuaki; Hashizume, Tsuneo; Honma, Masamitsu

2016-05-01

Sensitivity and/or specificity of the in vivo erythrocyte micronucleus (MN) and transgenic rodent mutation (TGR) tests to detect rodent carcinogens and non-carcinogens were investigated. The Carcinogenicity and Genotoxicity eXperience (CGX) dataset created by Kirkland et al. was used for the carcinogenicity and in vitro genotoxicity data, i.e., Ames and chromosome aberration (CA) tests. Broad literature surveys were conducted to gather in vivo MN or TGR test data to add to the CGX dataset. Genotoxicity data in vitro were also updated slightly. Data on 379 chemicals (293 carcinogens and 86 non-carcinogens) were available for the in vivo MN test; sensitivity, specificity or concordances were calculated as 41.0%, 60.5% or 45.4%, respectively. For the TGR test, data on 80 chemicals (76 carcinogens and 4 non-carcinogens) were available; sensitivity was calculated as 72.4%. Based on the recent guidance on genotoxicity testing strategies, performance (sensitivity/specificity) of the following combinations was calculated; Ames+in vivo MN (68.7%/45.3%), Ames+TGR (83.8%/not calculated (nc)), Ames+in vitro CA+in vivo MN (80.8%/21.3%), Ames+in vitro CA+TGR (89.1%/nc), Ames+in vivo MN+TGR (87.5%/nc), Ames+in vitro CA+in vivo MN+TGR (89.3%/nc). Relatively good balance in performance was shown by the Ames+in vivo MN in comparison with Ames+in vitro CA (74.3%/37.5%). Ames+TGR and Ames+in vivo MN+TGR gave even higher sensitivity, but the specificity could not be calculated (too few TGR data on non-carcinogens). This indicates that in vivo MN and TGR tests are both useful as in vivo tests to detect rodent carcinogens. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Toxic Elements in Tobacco and in Cigarette Smoke: Inflammation and Sensitization

PubMed Central

Pappas, R.S.

2015-01-01

Biochemically and pathologically, there is strong evidence for both atopic and nonatopic airway sensitization, hyperresponsiveness, and inflammation as a consequence of exposure to tobacco mainstream or sidestream smoke particulate. There is growing evidence for the relation between exposure to mainstream and sidestream smoke and diseases resulting from reactive oxidant challenge and inflammation directly as a consequence of the combined activity of neutrophils, macrophages, dendritic cells, eosinophils, basophils, as a humoral immunological consequence of sensitization, and that the metal components of the particulate play a role in adjuvant effects. As an end consequence, carcinogenicity is a known outcome of chronic inflammation. Smokeless tobacco has been evaluated by the IARC as a group 1 carcinogen. Of the many harmful constituents in smokeless tobacco, oral tissue metallothionein gradients suggest that metals contribute to the toxicity from smokeless tobacco use and possibly sensitization. This work reviews and examines work on probable contributions of toxic metals from tobacco and smoke to pathology observed as a consequence of smoking and the use of smokeless tobacco. PMID:21799956

Summary of the National Toxicology Program benzidine dye initiative.

PubMed Central

Morgan, D L; Dunnick, J K; Goehl, T; Jokinen, M P; Matthews, H B; Zeiger, E; Mennear, J H

1994-01-01

The benzidine dye initiative is a research program established by the National Toxicology Program to generate an integrated body of scientific information regarding the potential health risks associated with exposure to benzidine- and benzidine-congener-derived dyes. Because an in-depth evaluation of each of the hundreds of benzidine-congener-derived dyes was considered impractical, the research program was designed to study the metabolism and disposition, genetic toxicity, and in vivo toxicity and carcinogenicity of two primary benzidine congeners, 3,3'-dimethylbenzidine and 3,3'-dimethoxybenzidine, and a select group of prototypical dyes derived from those amines. It was anticipated that by applying the basic information generated in these extensive studies, it would be possible to make regulatory decisions about other dyes after conducting only a minimal number of experiments such as studies of disposition and metabolism, and in vitro mutagenicity. This paper summarizes the results of studies conducted to evaluate the metabolism, disposition, mutagenicity, toxicity, and carcinogenicity of representative benzidine congeners and derived dyes. PMID:7925189

Hydroquinone: Environmental Pollution, Toxicity, and Microbial Answers

PubMed Central

Leitão, Ana Lúcia

2013-01-01

Hydroquinone is a major benzene metabolite, which is a well-known haematotoxic and carcinogenic agent associated with malignancy in occupational environments. Human exposure to hydroquinone can occur by dietary, occupational, and environmental sources. In the environment, hydroquinone showed increased toxicity for aquatic organisms, being less harmful for bacteria and fungi. Recent pieces of evidence showed that hydroquinone is able to enhance carcinogenic risk by generating DNA damage and also to compromise the general immune responses which may contribute to the impaired triggering of the host immune reaction. Hydroquinone bioremediation from natural and contaminated sources can be achieved by the use of a diverse group of microorganisms, ranging from bacteria to fungi, which harbor very complex enzymatic systems able to metabolize hydroquinone either under aerobic or anaerobic conditions. Due to the recent research development on hydroquinone, this review underscores not only the mechanisms of hydroquinone biotransformation and the role of microorganisms and their enzymes in this process, but also its toxicity. PMID:23936816

Deleterious Effects of Mycotoxin Combinations Involving Ochratoxin A

PubMed Central

Klarić, Maja Šegvić; Rašić, Dubravka; Peraica, Maja

2013-01-01

Ochratoxin A (OTA) is a nephrotoxic mycotoxin with carcinogenic properties. Its presence was detected in various foodstuffs all over the world but with significantly higher frequency and concentrations in areas with endemic nephropathy (EN). Even though food is often contaminated with more than one mycotoxin, earlier studies focused on the occurrence and toxicology of only OTA. Only a limited number of surveys showed that OTA co-occurs in food with mycotoxins (citrinin-CIT, penicilic acid, fumonisin B1-FB1, aflatoxins-AF) which exert nephrotoxic, carcinogenic or carcinogen-promoting activity. This review summarises the findings on OTA and its co-occurrence with the mentioned mycotoxins in food as well as experimental data on their combined toxicity. Most of the tested mycotoxin mixtures involving OTA produced additive or synergistic effects in experimental models suggesting that these combinations represent a significant health hazard. Special attention should be given to mixtures that include carcinogenic and cancer-promoting mycotoxins. PMID:24189375

Soil quality in the Lomellina area using in vitro models and ecotoxicological assays

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baderna, Diego, E-mail: diego.baderna@marionegri.it; Colombo, Andrea; Romeo, Margherita

2014-08-15

Soil quality is traditionally evaluated by chemical characterization to determine levels of pollutants. Biological tools are now employed for soil monitoring since they can take account of the global biological effects induced by all xenobiotics. A combined monitoring of soils based on chemical analyses, human-related in vitro models and ecotoxicological assay was applied in the Lomellina, a semirural area of northern Italy. Chemical characterization indicated overall good quality of the soils, with low levels of toxic and carcinogenic pollutants such as heavy metals, PAHs, PCDD/Fs and PCBs. HepG2 cells were used as a model for the human liver and BALB/cmore » 3T3 cells to evaluate carcinogenic potential. Cells were treated with soil extractable organic matter (EOM) and the MTS assay, DNA release and morphological transformation were selected as endpoints for toxicity and carcinogenicity. Soil EOMs induced dose-dependent inhibition of cell growth at low doses and cytotoxicity only at doses of 500 and 1000 mg soil equivalents/ml. Potential issues for human health can be hypothesized after ingestion of soil samples from some sites. No statistically significant inductions of foci were recorded after exposure to EOMs, indicating that the levels of the soil-extracted organic pollutants were too low to induce carcinogenesis in our experimental conditions. An acute phytotoxicity test and studies on Caenorhabditis elegans were used as ecotoxicological assays for plants and small invertebrates. No significant alerts for ecotoxicity were found. In this proposed case study, HepG2 cells detected differences in the toxicity of soil EOMs, indicating that this cell line could be appropriate to assess the potential harm caused by the ingestion of contaminated soil. Additional information on the carcinogenic potential of mixtures was provided by the cell transformation assay, strengthening the combined approach. - Highlights: • A combined approach for evaluation of soil quality is proposed. • Organic extracts from investigated soils inhibited HepG2 cell proliferation. • The carcinogenic potential of extracts was evaluated by cell transformation assay. • Potential alerts were estimated after ingestion of soils. • Caenorhabditis elegans and phytotest were used to evaluate ecological effects.« less

Spatiotemporal Characteristics and Health Risk Assessment of Heavy Metals in PM2.5 in Zhejiang Province

PubMed Central

Wang, Xiaofeng; He, Shengliang; Chen, Shuchang; Zhang, Yongli; Wang, Aihong; Luo, Jinbin; Ye, Xialiang; Mo, Zhe; Wu, Lizhi; Xu, Peiwei; Cai, Gaofeng; Chen, Zhijian; Lou, Xiaoming

2018-01-01

The spatiotemporal characteristics and human health risks of 12 heavy metals (Al, As, Be, Cd, Cr, Hg, Mn, Ni, Pb, Sb, Se, and Tl) in fine particulate matter (PM2.5) in Zhejiang Province were investigated. The annual average PM2.5 concentration was 58.83 µg/m3 in 2015 in Zhejiang. Element contents in PM2.5 varied greatly with the season and locations. Al, Pb, and Mn were the most abundant elements among the studied metal(loid)s in PM2.5. The non-carcinogenic risks of the 12 elements through inhalation and dermal contact exposure were lower than the safe level for children and adults. However, there were potential non-carcinogenic risks of Tl, As, and Sb for children and Tl for adults through ingestion exposure. The carcinogenic risks from As, Be, Cd, Cr, Pb, and Ni through inhalation exposure were less than the acceptable level (1 × 10−4) for children and adults. Pb may carry a potential carcinogenic risk for both children and adults through ingestion. More attention should be paid to alleviate non-carcinogenic and carcinogenic health risks posed by particle-bound toxic elements through ingestion exposure. PMID:29587346

Recent Developments in Toxico-Cheminformatics; Supporting ...

EPA Pesticide Factsheets

EPA's National Center for Computational Toxicology is building capabilities to support a new paradigm for toxicity screening and prediction through the harnessing of legacy toxicity data, creation of data linkages, and generation of new high-content and high-thoughput screening data. In association with EPA's ToxCast, ToxRefDB, and ACToR projects, the DSSTox project provides cheminformatics support and, in addition, is improving public access to quality structure-annotated chemical toxicity information in less summarized forms than traditionally employed in SAR modeling, and in ways that facilitate data-mining and data read-across. The latest DSSTox version of the Carcinogenic Potency Database file (CPDBAS) illustrates ways in which various summary definitions of carcinogenic activity can be employed in modeling and data mining. DSSTox Structure-Browser provides structure searchability across all published DSSTox toxicity-related inventory, and is enabling linkages between previously isolated toxicity data resources associated with environmental and industrial chemicals. The public DSSTox inventory also has been integrated into PubChem, allowing a user to take full advantage of PubChem structure-activity and bioassay clustering features. Phase I of the ToxCast project is generating high-throughput screening data from several hundred biochemical and cell-based assays for a set of 320 chemicals, mostly pesticide actives with rich toxicology profiles. Incorporating

Therapeutic properties of green tea against environmental insults

PubMed Central

Chen, Lixia; Mo, Huanbiao; Zhao, Ling; Gao, Weimin; Wang, Shu; Cromie, Meghan M; Lu, Chuanwen; Wang, Jia-Sheng; Shen, Chwan-Li

2016-01-01

Pesticides, smoke, mycotoxins, polychlorinated biphenyls, and arsenic are the most common environmental toxins and toxicants to humans. These toxins and toxicants may impact on human health at the molecular (DNA, RNA, or protein), organelle (mitochondria, lysosome, or membranes), cellular (growth inhibition or cell death), tissue, organ, and systemic levels. Formation of reactive radicals, lipid peroxidation, inflammation, genotoxicity, hepatotoxicity, embryotoxicity, neurological alterations, apoptosis, and carcinogenic events are some of the mechanisms mediating the toxic effects of the environmental toxins and toxicants. Green tea, the non-oxidized and non-fermented form of tea that contains several polyphenols, including green tea catechins, exhibits protective effects against these environmental toxins and toxicants in preclinical studies and to a much-limited extent, in clinical trials. The protective effects are collectively mediated by antioxidant, anti-inflammatory, anti-mutagenic, hepato- and neuroprotective, and anti-carcinogenic activities. In addition, green tea modulates signaling pathway including NFκB and ERK pathways, preserves mitochondrial membrane potential, inhibits caspase-3 activity, down-regulates pro-apoptotic proteins, and induces the phase II detoxifying pathway. The bioavailability and metabolism of green tea and its protective effects against environmental insults induced by pesticides, smoke, mycotoxins, polychlorinated biphenyls, and arsenic are reviewed in this paper. Future studies with emphasis on clinical trials should identify biomarkers of green tea intake, examine the mechanisms of action of green tea polyphenols, and investigate potential interactions of green tea with other toxicant-modulating dietary factors. PMID:27723473

General aspects of metal toxicity.

PubMed

Kozlowski, H; Kolkowska, P; Watly, J; Krzywoszynska, K; Potocki, S

2014-01-01

This review is focused on the general mechanisms of metal toxicity in humans. The possible and mainly confirmed mechanisms of their action are discussed. The metals are divided into four groups due to their toxic effects. First group comprises of metal ions acting as Fenton reaction catalyst mainly iron and copper. These types of metal ions participate in generation of the reactive oxygen species. Metals such as nickel, cadmium and chromium are considered as carcinogenic agents. Aluminum, lead and tin are involved in neurotoxicity. The representative of the last group is mercury, which may be considered as a generally toxic metal. Fenton reaction is a naturally occurring process producing most active oxygen species, hydroxyl radical: Fe(2+) + He2O2 ↔ Fe(3+) + OH(-) + OH(•) It is able to oxidize most of the biomolecules including DNA, proteins, lipids etc. The effect of toxicity depends on the damage of molecules i.e. production site of the hydroxyl radical. Chromium toxicity depends critically on its oxidation state. The most hazardous seems to be Cr(6+) (chromates) which are one of the strongest inorganic carcinogenic agents. Cr(6+) species act also as oxidative agents damaging among other nucleic acids. Redox inactive Al(3+), Cd(2+) or Hg(2+) may interfere with biology of other metal ions e.g. by occupying metal binding sites in biomolecules. All these aspects will be discussed in the review.

Analysis of 23 polycyclic aromatic hydrocarbons in smokeless tobacco by gas chromatography-mass spectrometry

PubMed Central

Stepanov, Irina; Villalta, Peter W.; Knezevich, Aleksandar; Jensen, Joni; Hatsukami, Dorothy; Hecht, Stephen S.

2009-01-01

Smokeless tobacco contains 28 known carcinogens and causes precancerous oral lesions and oral and pancreatic cancer. A recent study conducted by our research team identified 8 different polycyclic aromatic hydrocarbons (PAH) in U.S. moist snuff, encouraging further investigations of this group of toxicants and carcinogens in smokeless tobacco products. In this study, we developed a gas chromatography-mass spectrometry method that allows simultaneous analysis of 23 various PAH in smokeless tobacco after a simple two-step extraction and purification procedure. The method produced coefficients of variation under 10% for most PAH. The limits of quantitation for different PAH varied between 0.3 ng/g tobacco and 11 ng/g tobacco, starting with a 300-mg sample. The recovery of the stable isotope-labeled internal standards averaged 87%. The method was applied to analysis of 23 moist snuff samples that include various flavors of the most popular U.S. moist snuff brands, as well as 17 samples representing the currently marketed brands of spit-free tobacco pouches, a relatively new type of smokeless tobacco. The sum of all detected PAH in conventional moist snuff averaged 11.6 (± 3.7) µg/g dry weight, 20% of this amount being comprised by carcinogenic PAH. The levels of PAH in new spit-free tobacco products were much lower than those in moist snuff, the sum of all detected PAH averaging 1.3 (±0.28) µg/g dry weight. Our findings render PAH one of the most prevalent groups of carcinogens in smokeless tobacco, along with tobacco-specific nitrosamines. Urgent measures are required from the U.S. tobacco industry to modify manufacturing processes so that the levels of these toxicants and carcinogens in the U.S. moist snuff are greatly reduced. PMID:19860436

Speciation and Toxic Emissions from On road Vehicles, and Particulate Matter Emissions from Light-Duty Gasoline Vehicles in MOVES201X

EPA Science Inventory

Updated methane, non-methane organic gas, and volatile organic compound calculations based on speciation data. Updated speciation and toxic emission rates for new model year 2010 and later heavy-duty diesel engines. Updated particulate matter emission rates for 2004 and later mod...

Comparative Biochemistry and Metabolism. Part 1. Carcinogenesis

DTIC Science & Technology

1982-08-01

1968), Nitrosamine-induced carcino- genesis. The alkylation of nucleic acids of the rat by N-methvl- N- nitrosourea , dimethylnitrosamine...inorganic reducing agent , hydrazine, is toxic and weakly carcinogenic. In earlier studies it was found that oral administration of a toxic dose of...metabolically activated to a methylatinj agent . Liver DNA from mice and hamsters contained considerably more 7-methyl- guanine and 0 6-methylguanine

New Toxico-Cheminformatics & Computational Toxicology ...

EPA Pesticide Factsheets

EPA’s National Center for Computational Toxicology is building capabilities to support a new paradigm for toxicity screening and prediction. The DSSTox project is improving public access to quality structure-annotated chemical toxicity information in less summarized forms than traditionally employed in SAR modeling, and in ways that facilitate data-mining, and data read-across. The DSSTox Structure-Browser provides structure searchability across all published DSSTox toxicity-related inventory, and is enabling linkages between previously isolated toxicity data resources. As of early March 2008, the public DSSTox inventory has been integrated into PubChem, allowing a user to take full advantage of PubChem structure-activity and bioassay clustering features. The most recent DSSTox version of the Carcinogenic Potency Database file (CPDBAS) illustrates ways in which various summary definitions of carcinogenic activity can be employed in modeling and data mining. Phase I of the ToxCastTM project is generating high-throughput screening data from several hundred biochemical and cell-based assays for a set of 320 chemicals, mostly pesticide actives, with rich toxicology profiles. Incorporating and expanding traditional SAR concepts into this new high-throughput and data-rich world pose conceptual and practical challenges, but also holds great promise for improving predictive capabilities.

Elevated Levels of Mercapturic Acids of Acrolein and Crotonaldehyde in the Urine of Chinese Women in Singapore Who Regularly Cook at Home

PubMed Central

Hecht, Stephen S.; Koh, Woon-Puay; Wang, Renwei; Chen, Menglan; Carmella, Steven G.; Murphy, Sharon E.; Yuan, Jian-Min

2015-01-01

Lung cancer is unusually common among non-smoking women in Southeastern Asia but the causes of this frequently fatal disease are not well understood. Several epidemiology studies indicate that inhalation of fumes from high temperature Chinese style cooking with a wok may be a cause. Only one previous study investigated uptake of potential toxicants and carcinogens by women who cook with a wok. We enrolled three-hundred twenty-eight non-smoking women from Singapore for this study. Each provided a spot urine sample and answered a questionnaire concerning their cooking habits and other factors. The urine samples were analyzed by liquid chromatography-tandem mass spectrometry for mercapturic acid metabolites of acrolein (3-hydroxypropylmercapturic acid), crotonaldehyde (3-hydroxy-1-methylpropylmercapturic acid), and benzene (S-phenylmercapturic acid), accepted biomarkers of uptake of these toxic and carcinogenic compounds. We observed statistically significant effects of wok cooking frequency on levels of 3-hydroxypropylmercapturic acid and 3-hydroxy-1-methylpropylmercapturic acid, but not S-phenylmercapturic acid. Women who cooked greater than 7 times per week had a geometric mean of 2600 (95% CI, 2189-3090) pmol/mg creatinine 3-hydroxypropylmercapturic acid compared to 1901 (95% CI, 1510-2395) pmol/mg creatinine when cooking less than once per week (P for trend 0.018). The corresponding values for 3-hydroxy-1-methylpropylmercapturic acid were 1167 (95% CI, 1022-1332) and 894 (95% CI, 749-1067) pmol/mg creatinine (P for trend 0.008). We conclude that frequent wok cooking leads to elevated exposure to the toxicants acrolein and crotonaldehyde, but not benzene. Kitchens should be properly ventilated to decrease exposure to potentially toxic and carcinogenic fumes produced during Chinese style wok cooking. PMID:25807518

Tobacco toxicant exposure in cigarette smokers who use or do not use other tobacco products.

PubMed

Nollen, Nicole L; Mayo, Matthew S; Clark, Lauren; Cox, Lisa Sanderson; Khariwala, Samir S; Pulvers, Kim; Benowitz, Neal L; Ahluwalia, Jasjit S

2017-10-01

Non-cigarette other tobacco products (OTP; e.g., cigarillos, little cigars) are typically used in combination with cigarettes, but limited data exists on the tobacco toxicant exposure profiles of dual cigarette-OTP (Cig-OTP) users. This study examined biomarkers of nicotine and carcinogen exposure in cigarette smokers who used or did not use OTP. 111 Cig-OTP and 111 cigarette only (Cig Only) users who smoked equivalent cigarettes per day were matched on age (< 40, >=40), race (African American, White), and gender. Participants reported past 7-day daily use of cigarettes and OTP and provided urine for nicotine, cotinine, total nicotine equivalents (TNE) and total NNAL concentrations. Cig-OTP users reported greater past 7-day tobacco use (15.9 versus 13.0 products/day, p<0.01) but had significantly lower creatinine-normalized nicotine (606 versus 1301ng/mg), cotinine (1063 versus 2125ng/mg), TNE (28 versus 57 nmol/mg) and NNAL (251 versus 343pg/mg) than Cig Only users (p<0.001). Cig-OTP users had lower levels of nicotine and metabolites of a lung carcinogen relative to Cig-Only users, but concentrations of toxicants among Cig-OTP users were still at levels that place smokers at great risk from the detrimental health effects of smoking. Our study finds that nicotine and carcinogen exposure in Cig-OTP users are lower compared to cigarette only users, but still likely to be associated with substantial harm. A better understanding of why toxicant levels may be lower in Cig-OTP is an important area for future study. Copyright © 2017 Elsevier B.V. All rights reserved.

Interactions of the interferon system with cellular metabolism

NASA Technical Reports Server (NTRS)

Sonnenfeld, Gerald

1986-01-01

The results of studies concerning the interaction of the interferon (Inf) system with the activities of carcinogens, tumor promoters, and cytochrome P-450 are presented. The results show that the addition of a tumor promoter (TPA or 4-O-methyl-TPA) to a tissue culture enhances virus-induced Inf-gamma production, suggesting a potential value of tumor promoters in the biosynthesis of commercial Inf. On the other hand, the carcinogens were reported to inhibit the induction of Inf-alpha/beta in cultured cells and in intact animals (with no effect on the administered or preformed Inf). The demonstration of a correlation between the carcinogenic potential of a compound and its inhibitive effect on Inf production suggests a possible use of the Inf production assay in the evaluation of the carcinogenicity of chemicals. In addition, it was shown that the induction of Inf-alpha/beta as well as the administration of this Inf depresses the levels of rat liver cytochrome P-450 which is responsible for binding lipophilic drugs, steroids, and carcinogens, thus increasing the toxicity of the respective chemical.

Concentrations, sources and human health risk of inhalation exposure to air toxics in Edmonton, Canada.

PubMed

Bari, Md Aynul; Kindzierski, Warren B

2017-04-01

With concern about levels of air pollutants in recent years in the Capital Region of Alberta, an investigation of ambient concentrations, sources and potential human health risk of hazardous air pollutants (HAPs) or air toxics was undertaken in the City of Edmonton over a 5-year period (2009-2013). Mean concentrations of individual HAPs in ambient air including volatile organic compounds (VOCs), polycyclic aromatic hydrocarbons (PAHs) and trace metals ranged from 0.04 to 1.73 μg/m 3 , 0.01-0.54 ng/m 3 , and 0.05-3.58 ng/m 3 , respectively. Concentrations of benzene, naphthalene, benzo(a)pyrene (BaP), arsenic, manganese and nickel were far below respective annual Alberta Ambient Air Quality Objectives. Carcinogenic and non-carcinogenic risk of air toxics were also compared with risk levels recommended by regulatory agencies. Positive matrix factorization identified six air toxics sources with traffic as the dominant contributor to total HAPs (4.33 μg/m 3 , 42%), followed by background/secondary organic aerosol (SOA) (1.92 μg/m 3 , 25%), fossil fuel combustion (0.92 μg/m 3 , 11%). On high particulate air pollution event days, local traffic was identified as the major contributor to total HAPs compared to background/SOA and fossil fuel combustion. Carcinogenic risk values of traffic, background/SOA and metals industry emissions were above the USEPA acceptable level (1 × 10 -6 ), but below a tolerable risk (1 × 10 -4 ) and Alberta benchmark (1 × 10 -5 ). These findings offer useful preliminary information about current ambient air toxics levels, dominant sources and their potential risk to public health; and this information can support policy makers in the development of appropriate control strategies if required. Copyright © 2017 Elsevier Ltd. All rights reserved.

Tumor initiating activities of various derivatives of benz(a)anthracene and 7, 12-dimethyl-benz(a)anthracene in mouse skin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Slaga, T.J.; Gleason, G.L.; DiGiovanni, J.

Current information indicates that polycyclic aromatic hydrocarbons (PAH) exert their toxic, mutagenic, and carcinogenic activities after they have been metabolically activated by target cells to reactive epoxides. The results obtained from IN VIVO and IN VITRO binding, mutagenicity, metabolism, and carcinogenicity studies have led to the conclusion that BP-7, 8-diol is a proximate carcinogenic metabolite of BP, and the BP-diol-epoxide is an ultimate carcinogenic metabolite of BP. Recent results concerning the strong carcinogenicity of BP-7..beta.., 8..cap alpha..-diol-9..cap alpha..,10..cap alpha..-epoxide in newborn mice and in mouse skin strongly indicate that it is the ultimate carcinogenic metabolite of BP. Since diol-epoxides maymore » be responsible for the carcinogenicity of PAH other than BP, diols and diol-epoxides as well as other derivatives of PAH were tested for skin tumor-initiation in a two-stage system of tumorigenesis. In addition, since activation of methylated PAH may involve the side-chain methyl group, the skin tumor-initiating activity of various side-chain derivatives of methylated PA were determined. In this report, the skin tumor initiation of various derivatives of a nonmethylated PAH, BA as well as a methylated PAH, DMBA are compared. The data suggest that bay region diol-epoxides may be important in BA and DMBA carcinogenicity in mice which is supportive of the theory proposed by Jerina and co-workers which predicts that diol-epoxides in the bay region are the major determinants of PAH carcinogenicity.« less

NTP technical report on comparative toxicity and carcinogenicity studies of o-nitrotoluene and o-toluidine hydrochloride. (Cas Nos. 88-72-2 and 636-21-5) administered in feed to male f344/n rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Elwell, M.R.

1996-03-01

;Contents: Introduction (Physical and Chemical Properties, Production, Use, and Exposure, Disposition and Metabolism, Toxicity, Study Rationale and Design); Materials and Methods (Procurement and Characterization of 0-Nitroluene and o-Toluidine Hydrochloride, Preparation and Analysis of Dose Formulations, Preparation of Antibiotic Mixture, Toxicity Study Designs, Statistical Methods, Quality Assurance); Results (26-Week Feed Studies in Male F344/N Rats).

Exploring the Molecular Mechanisms of Nickel-Induced Genotoxicity and Carcinogenicity: A Literature Review

PubMed Central

Cameron, Keyuna S.; Buchner, Virginia; Tchounwou, Paul B.

2011-01-01

Nickel, a naturally occurring element that exists in various mineral forms, is mainly found in soil and sediment, and its mobilization is influenced by the physicochemical properties of the soil. Industrial sources of nickel include metallurgical processes such as electroplating, alloy production, stainless steel, and nickel-cadmium batteries. Nickel industries, oil- and coal-burning power plants, and trash incinerators have been implicated in its release into the environment. In humans, nickel toxicity is influenced by the route of exposure, dose, and solubility of the nickel compound. Lung inhalation is the major route of exposure for nickel-induced toxicity. Nickel may also be ingested or absorbed through the skin. The primary target organs are the kidneys and lungs. Other organs such as the liver, spleen, heart and testes may also be affected to a lesser extent. Although the most common health effect is an allergic reaction, research has also demonstrated that nickel is carcinogenic to humans. The focus of the present review is on recent research concerning the molecular mechanisms of nickel-induced genotoxicity and carcinogenicity. We first present a background on the occurrence of nickel in the environment, human exposure, and human health effects. PMID:21905451

Prioritization of reproductive toxicants in unconventional oil and gas operations using a multi-country regulatory data-driven hazard assessment.

PubMed

Inayat-Hussain, Salmaan H; Fukumura, Masao; Muiz Aziz, A; Jin, Chai Meng; Jin, Low Wei; Garcia-Milian, Rolando; Vasiliou, Vasilis; Deziel, Nicole C

2018-08-01

Recent trends have witnessed the global growth of unconventional oil and gas (UOG) production. Epidemiologic studies have suggested associations between proximity to UOG operations with increased adverse birth outcomes and cancer, though specific potential etiologic agents have not yet been identified. To perform effective risk assessment of chemicals used in UOG production, the first step of hazard identification followed by prioritization specifically for reproductive toxicity, carcinogenicity and mutagenicity is crucial in an evidence-based risk assessment approach. To date, there is no single hazard classification list based on the United Nations Globally Harmonized System (GHS), with countries applying the GHS standards to generate their own chemical hazard classification lists. A current challenge for chemical prioritization, particularly for a multi-national industry, is inconsistent hazard classification which may result in misjudgment of the potential public health risks. We present a novel approach for hazard identification followed by prioritization of reproductive toxicants found in UOG operations using publicly available regulatory databases. GHS classification for reproductive toxicity of 157 UOG-related chemicals identified as potential reproductive or developmental toxicants in a previous publication was assessed using eleven governmental regulatory agency databases. If there was discordance in classifications across agencies, the most stringent classification was assigned. Chemicals in the category of known or presumed human reproductive toxicants were further evaluated for carcinogenicity and germ cell mutagenicity based on government classifications. A scoring system was utilized to assign numerical values for reproductive health, cancer and germ cell mutation hazard endpoints. Using a Cytoscape analysis, both qualitative and quantitative results were presented visually to readily identify high priority UOG chemicals with evidence of multiple adverse effects. We observed substantial inconsistencies in classification among the 11 databases. By adopting the most stringent classification within and across countries, 43 chemicals were classified as known or presumed human reproductive toxicants (GHS Category 1), while 31 chemicals were classified as suspected human reproductive toxicants (GHS Category 2). The 43 reproductive toxicants were further subjected to analysis for carcinogenic and mutagenic properties. Calculated hazard scores and Cytoscape visualization yielded several high priority chemicals including potassium dichromate, cadmium, benzene and ethylene oxide. Our findings reveal diverging GHS classification outcomes for UOG chemicals across regulatory agencies. Adoption of the most stringent classification with application of hazard scores provides a useful approach to prioritize reproductive toxicants in UOG and other industries for exposure assessments and selection of safer alternatives. Copyright © 2018 Elsevier Ltd. All rights reserved.

Genetic heterogeneity among slow acetylator N-acetyltransferase 2 phenotypes in cryopreserved human hepatocytes.

PubMed

Doll, Mark A; Hein, David W

2017-07-01

Genetic polymorphisms in human N-acetyltransferase 2 (NAT2) modify the metabolism of numerous drugs and carcinogens. These genetic polymorphisms modify both drug efficacy and toxicity and cancer risk associated with carcinogen exposure. Previous studies have suggested phenotypic heterogeneity among different NAT2 slow acetylator genotypes. NAT2 phenotype was investigated in vitro and in situ in samples of human hepatocytes obtained from various NAT2 slow and intermediate NAT2 acetylator genotypes. NAT2 gene dose response (NAT2*5B/*5B > NAT2*5B/*6A > NAT2*6A/*6A) was observed towards the N-acetylation of the NAT2-specific drug sulfamethazine by human hepatocytes both in vitro and in situ. N-acetylation of 4-aminobiphenyl, an arylamine carcinogen substrate for both N-acetyltransferase 1 and NAT2, showed the same trend both in vitro and in situ although the differences were not significant (p > 0.05). The N-acetylation of the N-acetyltransferase 1-specific substrate p-aminobenzoic acid did not follow this trend. In comparisons of NAT2 intermediate acetylator genotypes, differences in N-acetylation between NAT2*4/*5B and NAT2*4/*6B hepatocytes were not observed in vitro or in situ towards any of these substrates. These results further support phenotypic heterogeneity among NAT2 slow acetylator genotypes, consistent with differential risks of drug failure or toxicity and cancer associated with carcinogen exposure.

Mequindox Induced Genotoxicity and Carcinogenicity in Mice

PubMed Central

Liu, Qianying; Lei, Zhixin; Wu, Qin; Huang, Deyu; Xie, Shuyu; Wang, Xu; Pan, Yuanhu; Yuan, Zonghui

2018-01-01

Mequindox (MEQ), acting as an inhibitor of deoxyribonucleic acid (DNA) synthesis, is a synthetic heterocyclic N-oxides. To investigate the potential carcinogenicity of MEQ, four groups of Kun-Ming (KM) mice (50 mice/sex/group) were fed with diets containing MEQ (0, 25, 55, and 110 mg/kg) for one and a half years. The result showed adverse effects on body weights, feed consumption, hematology, serum chemistry, organ weights, relative organ weights, and incidence of tumors during most of the study period. Treatment-related changes in hematology, serum chemistry, relative weights and histopathological examinations revealed that the hematological system, liver, kidneys, and adrenal glands, as well as the developmental and reproductive system, were the main targets after MEQ administration. Additionally, MEQ significantly increased the frequency of micronucleated normochromatic erythrocytes in bone marrow cells of mice. Furthermore, MEQ increased the incidence of tumors, including mammary fibroadenoma, breast cancer, corticosuprarenaloma, haemangiomas, hepatocarcinoma, and pulmonary adenoma. Interestingly, the higher incidence of tumors was noted in M25 mg/kg group, the lowest dietary concentration tested, which was equivalent to approximately 2.25 and 1.72 mg/kg b.w./day in females and males, respectively. It was assumed that the lower toxicity might be a reason for its higher tumor incidence in M25 mg/kg group. This finding suggests a potential relationships among the dose, general toxicity and carcinogenicity in vivo, and further study is required to reveal this relationship. In conclusion, the present study demonstrates that MEQ is a genotoxic carcinogen in KM mice. PMID:29692735

Mequindox Induced Genotoxicity and Carcinogenicity in Mice.

PubMed

Liu, Qianying; Lei, Zhixin; Wu, Qin; Huang, Deyu; Xie, Shuyu; Wang, Xu; Pan, Yuanhu; Yuan, Zonghui

2018-01-01

Mequindox (MEQ), acting as an inhibitor of deoxyribonucleic acid (DNA) synthesis, is a synthetic heterocyclic N -oxides. To investigate the potential carcinogenicity of MEQ, four groups of Kun-Ming (KM) mice (50 mice/sex/group) were fed with diets containing MEQ (0, 25, 55, and 110 mg/kg) for one and a half years. The result showed adverse effects on body weights, feed consumption, hematology, serum chemistry, organ weights, relative organ weights, and incidence of tumors during most of the study period. Treatment-related changes in hematology, serum chemistry, relative weights and histopathological examinations revealed that the hematological system, liver, kidneys, and adrenal glands, as well as the developmental and reproductive system, were the main targets after MEQ administration. Additionally, MEQ significantly increased the frequency of micronucleated normochromatic erythrocytes in bone marrow cells of mice. Furthermore, MEQ increased the incidence of tumors, including mammary fibroadenoma, breast cancer, corticosuprarenaloma, haemangiomas, hepatocarcinoma, and pulmonary adenoma. Interestingly, the higher incidence of tumors was noted in M25 mg/kg group, the lowest dietary concentration tested, which was equivalent to approximately 2.25 and 1.72 mg/kg b.w./day in females and males, respectively. It was assumed that the lower toxicity might be a reason for its higher tumor incidence in M25 mg/kg group. This finding suggests a potential relationships among the dose, general toxicity and carcinogenicity in vivo , and further study is required to reveal this relationship. In conclusion, the present study demonstrates that MEQ is a genotoxic carcinogen in KM mice.

Combining QSAR Modeling and Text-Mining Techniques to Link Chemical Structures and Carcinogenic Modes of Action.

PubMed

Papamokos, George; Silins, Ilona

2016-01-01

There is an increasing need for new reliable non-animal based methods to predict and test toxicity of chemicals. Quantitative structure-activity relationship (QSAR), a computer-based method linking chemical structures with biological activities, is used in predictive toxicology. In this study, we tested the approach to combine QSAR data with literature profiles of carcinogenic modes of action automatically generated by a text-mining tool. The aim was to generate data patterns to identify associations between chemical structures and biological mechanisms related to carcinogenesis. Using these two methods, individually and combined, we evaluated 96 rat carcinogens of the hematopoietic system, liver, lung, and skin. We found that skin and lung rat carcinogens were mainly mutagenic, while the group of carcinogens affecting the hematopoietic system and the liver also included a large proportion of non-mutagens. The automatic literature analysis showed that mutagenicity was a frequently reported endpoint in the literature of these carcinogens, however, less common endpoints such as immunosuppression and hormonal receptor-mediated effects were also found in connection with some of the carcinogens, results of potential importance for certain target organs. The combined approach, using QSAR and text-mining techniques, could be useful for identifying more detailed information on biological mechanisms and the relation with chemical structures. The method can be particularly useful in increasing the understanding of structure and activity relationships for non-mutagens.

Combining QSAR Modeling and Text-Mining Techniques to Link Chemical Structures and Carcinogenic Modes of Action

PubMed Central

Papamokos, George; Silins, Ilona

2016-01-01

There is an increasing need for new reliable non-animal based methods to predict and test toxicity of chemicals. Quantitative structure-activity relationship (QSAR), a computer-based method linking chemical structures with biological activities, is used in predictive toxicology. In this study, we tested the approach to combine QSAR data with literature profiles of carcinogenic modes of action automatically generated by a text-mining tool. The aim was to generate data patterns to identify associations between chemical structures and biological mechanisms related to carcinogenesis. Using these two methods, individually and combined, we evaluated 96 rat carcinogens of the hematopoietic system, liver, lung, and skin. We found that skin and lung rat carcinogens were mainly mutagenic, while the group of carcinogens affecting the hematopoietic system and the liver also included a large proportion of non-mutagens. The automatic literature analysis showed that mutagenicity was a frequently reported endpoint in the literature of these carcinogens, however, less common endpoints such as immunosuppression and hormonal receptor-mediated effects were also found in connection with some of the carcinogens, results of potential importance for certain target organs. The combined approach, using QSAR and text-mining techniques, could be useful for identifying more detailed information on biological mechanisms and the relation with chemical structures. The method can be particularly useful in increasing the understanding of structure and activity relationships for non-mutagens. PMID:27625608

The association of the original OSHA chemical hazard communication standard with reductions in acute work injuries/illnesses in private industry and the industrial releases of chemical carcinogens.

PubMed

Oleinick, Arthur

2014-02-01

OSHA predicted the original chemical Hazard Communication Standard (HCS) would cumulatively reduce the lost workday acute injury/illness rate for exposure events by 20% over 20 years and reduce exposure to chemical carcinogens. JoinPoint trend software identified changes in the rate of change of BLS rates for days away from work for acute injuries/illnesses during 1992-2009 for manufacturing and nonmanufacturing industries for both chemical, noxious or allergenic injury exposure events and All other exposure events. The annual percent change in the rates was used to adjust observed numbers of cases to estimate their association with the standard. A case-control study of EPA's Toxic Release Inventory 1988-2009 data compared carcinogen and non-carcinogens' releases. The study estimates that the HCS was associated with a reduction in the number of acute injuries/illnesses due to chemical injury exposure events over the background rate in the range 107,569-459,395 (Hudson method/modified BIC model) depending on whether the HCS is treated as a marginal or sole factor in the decrease. Carcinogen releases have declined at a substantially faster rate than control non-carcinogens. The previous HCS standard was associated with significant reductions in chemical event acute injuries/illnesses and chemical carcinogen exposures. © 2013 Wiley Periodicals, Inc.

Toxic metals in cigarettes and human health risk assessment associated with inhalation exposure.

PubMed

Benson, Nsikak U; Anake, Winifred U; Adedapo, Adebusayo E; Fred-Ahmadu, Omowunmi H; Ayejuyo, Olusegun O

2017-11-08

This study evaluated the concentrations of cadmium (Cd), copper (Cu), iron (Fe), manganese (Mn), lead (Pb), and zinc (Zn) in 10 branded cigarettes commonly consumed in Nigeria. Chemical sequential extraction method and pseudo-total metal digestion procedure were used for extraction of metals from filler tobacco and filter samples. Samples were analyzed using flame atomic absorption spectrometry (FAAS). The filler tobacco of cigarettes had Cd, Cu, Fe, Mn, Pb, and Zn concentrations in the ranges of 5.90-7.94, 18.26-34.94, 192.61-3494.05, 44.67-297.69, 17.21-74.78, and 47.02-167.31 μg/cigarette, respectively. The minimum and maximum concentrations in the filter samples were 8.67-12.34 μg/g of Cd, 1.77-36.48 μg/g of Cu, 1.83-15.27 μg/g of Fe, 3.82-7.44 μg/g of Mn, 4.09-13.78 μg/g of Pb, and 30.07-46.70 μg/g of Zn. The results of this study showed that the concentrations of heavy metals in the filler tobacco samples were consistently higher than those obtained for the cigarette filters except for Cd. Toxic metals were largely found in the most labile chemical fractions. Moderate to very high risks are found associated with potential exposure to Cd and Pb. The carcinogenic risks posed by Cd and Pb ranged between 1.87E-02 and 2.52E-02, 1.05E-03 and 4.76E-03, respectively, while the non-carcinogenic risk estimates for Cd and Pb were greater than 1.0 (HI > 1). Toxic metals in cigarette may have significant carcinogenic and non-carcinogenic health effects associated with inhalation exposure. Continuous monitoring and regulations of the ingredients of imported and locally produced tobacco products are advocated.

Analysis of quantitative data obtained from toxicity studies showing non-normal distribution.

PubMed

Kobayashi, Katsumi

2005-05-01

The data obtained from toxicity studies are examined for homogeneity of variance, but, usually, they are not examined for normal distribution. In this study I examined the measured items of a carcinogenicity/chronic toxicity study with rats for both homogeneity of variance and normal distribution. It was observed that a lot of hematology and biochemistry items showed non-normal distribution. For testing normal distribution of the data obtained from toxicity studies, the data of the concurrent control group may be examined, and for the data that show a non-normal distribution, non-parametric tests with robustness may be applied.

Proteomic analyses of the environmental toxicity of carcinogenic chemicals

EPA Science Inventory

Protein expression and posttranslational modifications consistently change in response to the exposure to environmental chemicals. Recent technological advances in proteomics provide new tools for more efficient characterization of protein expression and posttranslational modific...

Triadimefon

EPA Science Inventory

Triadimefon (CAS 43121-43-3) is a broad spectrum systemic fungicide. The nervous system is the most sensitive target and serves as the basis for most regulatory assessments. Triadimefon is also a carcinogen and reproductive toxicant at high doses in rodent models.

Malathion.

ERIC Educational Resources Information Center

Brenner, Loretta

1992-01-01

Discusses research findings about malathion, a widely used insecticide, concerning potential for human exposure; how malathion works and is used; toxicity; carcinogenicity; mutagenicity; associated birth defects; reproductive effects; effects on vision, diet, behavior, and immune systems; contaminants and analogues, synergists, residues, inert…

Oral Chromium Exposure and Toxicity

PubMed Central

Sun, Hong; Brocato, Jason

2015-01-01

Hexavalent chromium [Cr(VI)] is a known carcinogen when inhaled. However, inhalational exposure to Cr(VI) affects only a small portion of the population, mainly by occupational exposures. In contrast, oral exposure to Cr(VI) is widespread and affects many people throughout the globe. In 2008, the National Toxicology Program (NTP) released a 2-year study demonstrating that ingested Cr(VI) was carcinogenic in rats and mice. The effects of Cr(VI) oral exposure is mitigated by reduction in the gut, however a portion evades the reductive detoxification and reaches target tissues. Once Cr(VI) enters the cell, it ultimately gets reduced to Cr(III), which mediates its toxicity via induction of oxidative stress during the reduction while Cr intermediates react with protein and DNA. Cr(III) can form adducts with DNA that may lead to mutations. This review will discuss the potential adverse effects of oral exposure to Cr(VI) by presenting up-to-date human and animal studies, examining the underlying mechanisms that mediate Cr(VI) toxicity, as well as highlighting opportunities for future research. PMID:26231506

Fluorescence-based recombination assay for sensitive and specific detection of genotoxic carcinogens in human cells.

PubMed

Ireno, Ivanildce C; Baumann, Cindy; Stöber, Regina; Hengstler, Jan G; Wiesmüller, Lisa

2014-05-01

In vitro genotoxicity tests are known to suffer from several shortcomings, mammalian cell-based assays, in particular, from low specificities. Following a novel concept of genotoxicity detection, we developed a fluorescence-based method in living human cells. The assay quantifies DNA recombination events triggered by DNA double-strand breaks and damage-induced replication fork stalling predicted to detect a broad spectrum of genotoxic modes of action. To maximize sensitivities, we engineered a DNA substrate encompassing a chemoresponsive element from the human genome. Using this substrate, we screened various human tumor and non-transformed cell types differing in the DNA damage response, which revealed that detection of genotoxic carcinogens was independent of the p53 status but abrogated by apoptosis. Cell types enabling robust and sensitive genotoxicity detection were selected for the generation of reporter clones with chromosomally integrated DNA recombination substrate. Reporter cell lines were scrutinized with 21 compounds, stratified into five sets according to the established categories for identification of carcinogenic compounds: genotoxic carcinogens ("true positives"), non-genotoxic carcinogens, compounds without genotoxic or carcinogenic effect ("true negatives") and non-carcinogenic compounds, which have been reported to induce chromosomal aberrations or mutations in mammalian cell-based assays ("false positives"). Our results document detection of genotoxic carcinogens in independent cell clones and at levels of cellular toxicities <60 % with a sensitivity of >85 %, specificity of ≥90 % and detection of false-positive compounds <17 %. Importantly, through testing cyclophosphamide in combination with primary hepatocyte cultures, we additionally provide proof-of-concept for the identification of carcinogens requiring metabolic activation using this novel assay system.

Health Effects of UV Radiation

MedlinePlus

... Agency Search Search Main menu Environmental Topics Air Bed Bugs Chemicals and Toxics Environmental Information by Location Greener Living Health Land, Waste, and ... radiation from the sun and from tanning beds is classified as a human carcinogen by the ...

Prioritization of Louisiana Parishes based on Industrial Releases of Known or Suspected Carcinogens.

PubMed

Katner, Adrienne

2015-01-01

This investigation evaluated the geographic distribution of carcinogen releases by Louisiana industries to prioritize areas for regulatory oversight, research and monitoring, and to promote clinician awareness and vigilance. Data on estimated industry releases for the period between 1996 and 2011 were obtained from the US Environmental Protection Agency's Toxics Release Inventory. Chemicals associated with cancers of the prostate, lung, bladder, kidney, breast and non-Hodgkin lymphoma were identified. The Risk Screening Environmental Indicators model was used to derive measures or model scores based on chemical toxicity, fate and transport, and population characteristics. Parishes, chemicals, industries and media generating the highest model scores were identified. Parishes with the highest model scores were East Baton Rouge, Calcasieu, Caddo and St. John the Baptist. Clinicians should carefully monitor cancer cases in these areas, and if patients reside near or work in industry, an occupational and environmental history should be considered.

Two azole fungicides (carcinogenic triadimefon and non-carcinogenic myclobutanil) exhibit different hepatic cytochrome P450 activities in medaka fish.

PubMed

Lin, Chun-Hung; Chou, Pei-Hsin; Chen, Pei-Jen

2014-07-30

Conazoles are a class of imidazole- or triazole-containing drugs commonly used as fungicides in agriculture and medicine. The broad application of azole drugs has led to the contamination of surface aquifers receiving the effluent of municipal or hospital wastewater or agricultural runoff. Several triazoles are rodent carcinogens; azole pollution is a concern to environmental safety and human health. However, the carcinogenic mechanisms associated with cytochrome P450 enzymes (CYPs) of conazoles remain unclear. We exposed adult medaka fish (Oryzias latipes) to continuous aqueous solutions of carcinogenic triadimefon and non-carcinogenic myclobutanil for 7 to 20 days at sub-lethal or environmentally relevant concentrations and assessed hepatic CYP activity and gene expression associated with CYP-mediated toxicity. Both triadimefon and myclobutanil induced hepatic CYP3A activity, but only triadimefon enhanced CYP1A activity. The gene expression of cyp3a38, cyp3a40, pregnane x receptor (pxr), cyp26b, retinoid acid receptor γ1 (rarγ1) and p53 was higher with triadimefon than myclobutanil. As well, yeast-based reporter gene assay revealed that 4 tested conazoles were weak agonists of aryl hydrocarbon receptor (AhR). We reveal differential CYP gene expression with carcinogenic and non-carcinogenic conazoles in a lower vertebrate, medaka fish. Liver CYP-enzyme induction may be a key event in conazole-induced tumorigenesis. This information is essential to evaluate the potential threat of conazoles to human health and fish populations in the aquatic environment. Copyright © 2014 Elsevier B.V. All rights reserved.

Sensor & Model Enabled Water Quality & Security Assessment System for Situational Awareness of Water Distribution Networks

DTIC Science & Technology

2010-06-01

Scenario – 12 gallons of readily available toxic substance – pump ($150 rental) – wrench to open a fire hydrant ($10)  One (1) terrorist, or...6 Gallons Water General Comments Aflatoxin 7.6 Potent Carcinogen Aldicarb 1.1 Cycloheximide 2.1 LSD 0.2 Highly Toxic , Psychoactive Mercuric Chloride...Chlorfenvinphos, Formetanate Hydrochloride, Acrolein, Chloropicrin, Sodium chloroacetate, Thyoglycolate medium, Crotoxyphos, Glyphosate , Jimsonweed, Methanol

Application of the threshold of toxicological concern concept to pharmaceutical manufacturing operations.

PubMed

Dolan, David G; Naumann, Bruce D; Sargent, Edward V; Maier, Andrew; Dourson, Michael

2005-10-01

A scientific rationale is provided for estimating acceptable daily intake values (ADIs) for compounds with limited or no toxicity information to support pharmaceutical manufacturing operations. These ADIs are based on application of the "thresholds of toxicological concern" (TTC) principle, in which levels of human exposure are estimated that pose no appreciable risk to human health. The same concept has been used by the US Food and Drug Administration (FDA) to establish "thresholds of regulation" for indirect food additives and adopted by the Joint FAO/WHO Expert Committee on Food Additives for flavoring substances. In practice, these values are used as a statement of safety and indicate when no actions need to be taken in a given exposure situation. Pharmaceutical manufacturing relies on ADIs for cleaning validation of process equipment and atypical extraneous matter investigations. To provide practical guidance for handling situations where relatively unstudied compounds with limited or no toxicity data are encountered, recommendations are provided on ADI values that correspond to three categories of compounds: (1) compounds that are likely to be carcinogenic, (2) compounds that are likely to be potent or highly toxic, and (3) compounds that are not likely to be potent, highly toxic or carcinogenic. Corresponding ADIs for these categories of materials are 1, 10, and 100 microg/day, respectively.

Polyamines are traps for reactive intermediates in furan metabolism

PubMed Central

Peterson, Lisa A.; Phillips, Martin B.; Lu, Ding; Sullivan, Mathilde M.

2011-01-01

Furan is toxic and carcinogenic in rodents. Because of the large potential for human exposure, furan is classified as a possible human carcinogen. The detailed mechanism by which furan causes toxicity and cancer is not yet known. Since furan toxicity requires cytochrome P450-catalyzed oxidation of furan, we have characterized the urinary and hepatocyte metabolites of furan to gain insight into the chemical nature of the reactive intermediate. Previous studies in hepatocytes indicated that furan is oxidized to the reactive α,β-unsaturated dialdehyde, cis-2-butene-1,4-dial (BDA), which reacts with glutathione (GSH) to form 2-(S-glutathionyl)-succinaldehyde (GSH-BDA). This intermediate forms pyrrole cross-links with cellular amines such as lysine and glutamine. In this report, we demonstrate that GSH-BDA also forms cross-links with ornithine, putrescine and spermidine when furan is incubated with rat hepatocytes. The relative levels of these metabolites are not completely explained by hepatocellular levels of the amines or by their reactivity with GSH-BDA. Mercapturic acid derivatives of the spermidine cross-links were detected in the urine of furan-treated rats, which indicates that this metabolic pathway occurs in vivo. Their detection in furan-treated hepatocytes and in urine from furan-treated rats indicates that polyamines may play an important role in the toxicity of furan PMID:21842885

IRIS TOXICOLOGICAL REVIEW AND SUMMARY DOCUMENTS FOR 1,1,1-TRICHLOROETHANE (PEER REVIEW PLAN)

EPA Science Inventory

EPA's assessment of the carcinogenic potential of 1,1,1-trichloroethane was entered into the IRIS database in 1988, and the assessment of noncancer effects following oral exposure was withdrawn from IRIS in 1991. The IRIS program prepared an update of the IRIS assessment for 1,1,...

Human health risk assessment of polycyclic aromatic hydrocarbons (PAHs) in smoked fish species from markets in Southern Nigeria.

PubMed

Tongo, Isioma; Ogbeide, Ozekeke; Ezemonye, Lawrence

2017-01-01

Polycyclic Aromatic Hydrocarbons (PAHs) levels in four commonly consumed smoked fish species from markets in Southern Nigeria were assessed to evaluate possible human health risks associated with consumption. Varying levels of PAH congeners were observed in the fish tissues with the highest total concentration of PAHs in Scomber scombrus . High concentrations of benzo(a)pyrene was observed in Clarias gariepinus and Ethmalosa fimbriata with values above the guideline value of 0.05 mg/kg. The Dietary Daily Intake (DDI) value for total PAHs (∑PAHs) was highest for S. scombrus while the DDI value for the total carcinogenic PAHs (∑CPAHs) was highest for E. fimbriata . Carcinogenic human health risk assessment using carcinogenic toxic equivalents (TEQ), indicated that consumption of E. fimbriata has a higher potential to cause carcinogenic risks. TEQ values for all the fish species were however, below the estimated screening value (SV) of 3.556 mg/kg, while the estimated cumulative excess cancer risk (ECR) for E. fimbriata and C. gariepinus and PAH4 index for all the assessed fish species exceeded threshold values indicating potential carcinogenic risk from consumption.

Genotoxic chemical carcinogens target inducible genes in vivo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hamilton, J.W.; McCaffrey, J.; Caron, R.M.

1994-12-31

Our laboratory is interested in whether carcinogen-induced DNA damage is distributed nonrandomly in the genome - that is, {open_quotes}targeted{close_quotes} to specific genes or gene regions in vivo. As an indirect measure of whether targeting occurs at the gene level, we have examined whether carcinogens differentially alter the expression of individual genes. We have compared the effects of model genotoxic carcinogens that principally induce either strand breaks, simple alkylations, bulky lesions, or DNA cross-links on the expression of several constitutive and inducible genes in a simple in vivo system, the chick embryo. Each agent was examined for its effects on genemore » expression over a 24 hour period corresponding to the period of maximal DNA damage and repair induced by each compound. The doses used in these studies represented the maximum doses that caused no overt toxicity over a 96 hour period but that induced significant levels of DNA damage. Our results demonstrate that inducible genes are targeted by chemical carcinogens. We hypothesize that such effects may be a result of DNA damage specifically altering DNA-protein interactions within the promoters of inducible genes.« less

Assessment of the toxic potential of polycyclic aromatic hydrocarbons (PAHs) affecting Gulf menhaden (Brevoortia patronus) harvested from waters impacted by the BP Deepwater Horizon Spill.

PubMed

Olson, Gregory M; Meyer, Buffy M; Portier, Ralph J

2016-02-01

Approximately 4.9 million barrels of crude oil and gas were released into the Gulf of Mexico (GoM) from April to July 2010 during the Deepwater Horizon (DWH) spill. This resulted in the possible contamination of marine organisms with polycyclic aromatic hydrocarbons (PAHs), USEPA identified constituents of concern. To determine the impact of the DWH oil spill, Gulf menhaden (Brevoortia patronus), a commercially harvested and significant trophic grazing species, was sampled from two Louisiana coastal regions between the years 2011-2013. Tissue extraction and GC/MS analysis demonstrated measurable concentrations of PAH within menhaden. Analysis yielded total PAHs, carcinogenic equivalents (BaP-TEQ), and mutagenic equivalents (BaP-MEQ) which provided an initial toxic potential assessment of this GoM Fishery. Gulf menhaden contained less total PAH concentrations in 2012 and significantly less in 2013 as compared to 2011 (p < 0.05) ranging from 7 ug/g tissue dry weight to 3 ng/g tissue dry weight. Carcinogenic and mutagenic PAHs were also significantly reduced (p < 0.05) over the three year period. The reduction of total PAH concentrations and the reduction of BaP-TEQs and MEQs between 2011 and 2013 indicates a diminished input of new source PAHs along with a reduction of carcinogenic and mutagenic PAHs in menhaden populations. The use of Gulf menhaden was successful in determining the acute toxic potential of PAHs contaminating the GoM in the years directly following the DWH spill event. Copyright © 2015 Elsevier Ltd. All rights reserved.

Respiratory carcinogenicity assessment of soluble nickel compounds.

PubMed Central

Oller, Adriana R

2002-01-01

The many chemical forms of nickel differ in physicochemical properties and biological effects. Health assessments for each main category of nickel species are needed. The carcinogenicity assessment of water-soluble nickel compounds has proven particularly difficult. Epidemiologic evidence indicates an association between inhalation exposures to nickel refinery dust containing soluble nickel compounds and increased risk of respiratory cancers. However, the nature of this association is unclear because of limitations of the exposure data, inconsistent results across cohorts, and the presence of mixed exposures to water-insoluble nickel compounds and other confounders that are known or suspected carcinogens. Moreover, well-conducted animal inhalation studies, where exposures were solely to soluble nickel, failed to demonstrate a carcinogenic potential. Similar negative results were seen in animal oral studies. A model exists that relates respiratory carcinogenic potential to the bioavailability of nickel ion at nuclear sites within respiratory target cells. This model helps reconcile human, animal, and mechanistic data for soluble nickel compounds. For inhalation exposures, the predicted lack of bioavailability of nickel ion at target sites suggests that water-soluble nickel compounds, by themselves, will not be complete human carcinogens. However, if inhaled at concentrations high enough to induce chronic lung inflammation, these compounds may enhance carcinogenic risks associated with inhalation exposure to other substances. Overall, the weight of evidence indicates that inhalation exposure to soluble nickel alone will not cause cancer; moreover, if exposures are kept below levels that cause chronic respiratory toxicity, any possible tumor-enhancing effects (particularly in smokers) would be avoided. PMID:12426143

An Analysis of the Role of Tobacco-Specific Nitrosamines in the Carcinogenicity of Tobacco Smoke

PubMed Central

Brown, Buddy G.; Borschke, August J.; Doolittle, David J.

2003-01-01

Cigarette smoke is a complex mixture consisting of more than 4500 chemicals, including several tobacco-specific nitrosamines (TSNA). TSNA typically form in tobacco during the post-harvest period, with some fraction being transferred into mainstream smoke when a cigarette is burned during use. The most studied of the TSNA is 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). NNK has been shown to be carcinogenic in laboratory animals. Studies examining the carcinogenicity of NNK frequently are conducted by injecting rodents with a single dose of 2.5 to 10 μmol of pure NNK; the amount of NNK contained in all of the mainstream smoke from about 3700 to 14,800 typical U.S. cigarettes. Extrapolated to a 70-kg smoker, the carcinogenic dose of pure NNK administered to rodents would be equivalent to the amount of NNK in all of the mainstream smoke of 22 to 87 million typical U.S. cigarettes. Furthermore, extrapolating results from rodent studies based on a single injection of pure NNK to establish a causative role for NNK in the carcinogenicity of chronic tobacco smoke exposure in humans is not consistent with basic pharmacological and toxicological principles. For example, such an approach fails to consider the effect of other smoke constituents upon the toxicity of NNK. In vitro studies demonstrate that nicotine, cotinine, and aqueous cigarette “tar” extract (ACTE) all inhibit the mutagenic activity of NNK. In vivo studies reveal that the formation of pulmonary DNA adducts in mice injected with NNK is inhibited by the administration of cotinine and mainstream cigarette smoke. Cigarette smoke has been shown to modulate the metabolism of NNK, providing a mechanism for the inhibitory effects of cigarette smoke and cigarette smoke constituents on NNK-induced tumorigenesis. NNK-related pulmonary DNA adducts have not been detected in rodents exposed to cigarette smoke, nor has the toxicity of tobacco smoke or tobacco smoke condensate containing marked reductions in TSNA concentrations been shown to be reduced in any biological assay. In summary, there is no experimental evidence to suggest that reduction of TSNA will reduce the mutagenic, cytotoxic, or carcinogenic potential of tobacco smoke. PMID:19330121

A call to expand regulation to all carcinogenic fibrous minerals

NASA Astrophysics Data System (ADS)

Baumann, F.; Steele, I.; Ambrosi, J.; Carbone, M.

2013-05-01

The regulatory term "asbestos" groups only the six fibrous minerals that were commercially used among approximately 400. The carcinogenicity of these six regulated minerals has been largely demonstrated and is related to fiber structure, fiber length/diameter ratio, and bio-persistence. From a public perception, the generic term "asbestos" refers to the fibrous minerals that cause asbestosis, mesothelioma and other cancers. However, other non-regulated fibrous minerals are potentially as dangerous as the regulatory asbestos because they share similar physical and chemical properties, epidemiological studies have demonstrated their relationship with asbestos-related diseases, and both in vitro and in vivo experiments have established the toxicity of these minerals. For example, the non-regulated asbestiform winchite and richterite minerals that contaminated the vermiculite mined from Libby, Montana, (USA) were associated with mesothelioma, lung cancer and asbestosis observed among the area's residents and miners. Many other examples of non-regulated carcinogenic fibrous minerals include, but are not limited to, antigorite, arfvedsonite, balangeroite, carlosturanite, erionite, fluoro-edenite, hornblende, mordenite, palygorskite, and sepiolite. To propose a regulatory definition that would provide protection from all carcinogenic fibers, we have conducted an interdisciplinary literature review to compare the characteristics of "asbestos" and of non-regulated mineral fibers that relate to carcinogenicity. We specifically studied two non-regulated fibrous minerals that are associated with asbestos-related diseases: the serpentine antigorite and the zeolite erionite. Both examples underscore the problem of regulation based on commercial, rather than scientific principles: 1) the occurrence of fibrous antigorite in materials used to pave roads has been correlated with high mesothelioma rates in New Caledonia. Antigorite was also the cause of asbestosis in Poland, and in vitro and in vivo studies have shown its toxic and carcinogenic properties; 2) the carcinogenic properties of erionite have been demonstrated, and erionite has been associated with a mesothelioma epidemic in Anatolia, Turkey. Erionite is also widespread in areas of north central USA, where it is contained in gravel paving stone, and is cause for concern due to increased commercial traffic. Numerous studies have shown that non-regulated fibrous materials pose similar health hazards to regulated "asbestos". An increase in human activities in areas where these fibrous minerals are present, such as in surficial rock and soil, will result in the generation of airborne dust, exposing people to carcinogenic fibers. The current limited regulation leads people to believe that only the six mineral fibers referred to as "asbestos" are dangerous. We propose that fibrous minerals should be regulated as a single group, as they have similar deleterious effects on the human body. Regulations would be simplified and more effective if they embrace all carcinogenic fibrous minerals.

HEALTH AND ENVIRONMENTAL EFFECTS DOCUMENT ...

EPA Pesticide Factsheets

Health and Environmental Effects Documents (HEEDS) are prepared for the Office of Solid Waste and Emergency Response (OSWER). This document series is intended to support listings under the Resource Conservation and Recovery Act (RCRA) as well as to provide health-related limits and goals for emergency and remedial actions under the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA). Both published literature and information obtained from Agency Program Office files are evaluated as they pertain to potential human health, aquatic life and environmental effects of hazardous waste constituents. Several quantitative estimates are presented provided sufficient data are available. For systemic toxicants, these include Reference Doses (RfDs) for chronic and subchronic exposures for both the inhalation and oral exposures. In the case of suspected carcinogens, RfDs may not be estimated. Instead, a carcinogenic potency factor, or q1*, is provided. These potency estimates are derived for both oral and inhalation exposures where possible. In addition, unit risk estimates for air and drinking water are presented based on inhalation and oral data, respectively. Reportable quantities (RQs) based on both chronic toxicity and carcinogenicity are derived. The RQ is used to determine the quantity of a hazardous substance for which notification is required in the event of a release as specified under CERCLA.

Carcinogenic compounds in alcoholic beverages: an update.

PubMed

Pflaum, Tabea; Hausler, Thomas; Baumung, Claudia; Ackermann, Svenja; Kuballa, Thomas; Rehm, Jürgen; Lachenmeier, Dirk W

2016-10-01

The consumption of alcoholic beverages has been classified as carcinogenic to humans by the International Agency for Research on Cancer (IARC) since 1988. More recently, in 2010, ethanol as the major constituent of alcoholic beverages and its metabolite acetaldehyde were also classified as carcinogenic to humans. Alcoholic beverages as multi-component mixtures may additionally contain further known or suspected human carcinogens as constituent or contaminant. This review will discuss the occurrence and toxicology of eighteen carcinogenic compounds (acetaldehyde, acrylamide, aflatoxins, arsenic, benzene, cadmium, ethanol, ethyl carbamate, formaldehyde, furan, glyphosate, lead, 3-MCPD, 4-methylimidazole, N-nitrosodimethylamine, pulegone, ochratoxin A, safrole) occurring in alcoholic beverages as identified based on monograph reviews by the IARC. For most of the compounds of alcoholic beverages, quantitative risk assessment provided evidence for only a very low risk (such as margins of exposure above 10,000). The highest risk was found for ethanol, which may reach exposures in ranges known to increase the cancer risk even at moderate drinking (margin of exposure around 1). Other constituents that could pose a risk to the drinker were inorganic lead, arsenic, acetaldehyde, cadmium and ethyl carbamate, for most of which mitigation by good manufacturing practices is possible. Nevertheless, due to the major effect of ethanol, the cancer burden due to alcohol consumption can only be reduced by reducing alcohol consumption in general or by lowering the alcoholic strength of beverages.

Mg co-ordination with potential carcinogenic molecule acrylamide: Spectroscopic, computational and cytotoxicity studies

NASA Astrophysics Data System (ADS)

Singh, Ranjana; Mishra, Vijay K.; Singh, Hemant K.; Sharma, Gunjan; Koch, Biplob; Singh, Bachcha; Singh, Ranjan K.

2018-03-01

Acrylamide (acr) is a potential toxic molecule produced in thermally processed food stuff. Acr-Mg complex has been synthesized chemically and characterized by spectroscopic techniques. The binding sites of acr with Mg were identified by experimental and computational methods. Both experimental and theoretical results suggest that Mg coordinated with the oxygen atom of Cdbnd O group of acr. In-vitro cytotoxicity studies revealed significant decrease in the toxic level of acr-Mg complex as compared to pure acr. The decrease in toxicity on complexation with Mg may be a useful step for future research to reduce the toxicity of acr.

Evaluation of human health risks posed by carcinogenic and non-carcinogenic multiple contaminants associated with consumption of fish from Taihu Lake, China.

PubMed

Yu, Yingxin; Wang, Xinxin; Yang, Dan; Lei, Bingli; Zhang, Xiaolan; Zhang, Xinyu

2014-07-01

The present study estimated the human daily intake and uptake of organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), polycyclic aromatic hydrocarbons (PAHs), and toxic trace elements [mercury (Hg), chromium (Cr), cadmium (Cd), and arsenic (As)] due to consumption of fish from Taihu Lake, China, and the associated potential health risks posed by these contaminants. The health risks posed by the contaminants were assessed using a risk quotient of the fish consumption rate to the maximum allowable fish consumption rate considering the contaminants for carcinogenic and non-carcinogenic effect endpoints. The results showed that fish consumption would not pose non-cancer risks. However, some species would cause a cancer risk. Relative risks of the contaminants were calculated to investigate the contaminant which posed the highest risk to humans. As a result, in view of the contaminants for carcinogenic effects, As was the contaminant which posed the highest risk to humans. However, when non-carcinogenic effects of the contaminants were considered, Hg posed the highest risk. The risk caused by PBDEs was negligible. The results demonstrated that traditional contaminants, such as As, Hg, DDTs (dichlorodiphenyltrichloroethane and its metabolites), and PCBs, require more attention in Taihu Lake than the other target contaminants. Copyright © 2014 Elsevier Ltd. All rights reserved.

76 FR 63623 - Board of Scientific Counselors, National Center for Environmental Health/Agency for Toxic...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-13

... Nutritional Biomarker Report: transfat analysis; update on ATSDR Science Symposium; update on Camp LeJeune; update on Environmental Health Tracking; presentation on hydraulic fracking; global health updates...

Metals, toxicity and oxidative stress.

PubMed

Valko, M; Morris, H; Cronin, M T D

2005-01-01

Metal-induced toxicity and carcinogenicity, with an emphasis on the generation and role of reactive oxygen and nitrogen species, is reviewed. Metal-mediated formation of free radicals causes various modifications to DNA bases, enhanced lipid peroxidation, and altered calcium and sulfhydryl homeostasis. Lipid peroxides, formed by the attack of radicals on polyunsaturated fatty acid residues of phospholipids, can further react with redox metals finally producing mutagenic and carcinogenic malondialdehyde, 4-hydroxynonenal and other exocyclic DNA adducts (etheno and/or propano adducts). Whilst iron (Fe), copper (Cu), chromium (Cr), vanadium (V) and cobalt (Co) undergo redox-cycling reactions, for a second group of metals, mercury (Hg), cadmium (Cd) and nickel (Ni), the primary route for their toxicity is depletion of glutathione and bonding to sulfhydryl groups of proteins. Arsenic (As) is thought to bind directly to critical thiols, however, other mechanisms, involving formation of hydrogen peroxide under physiological conditions, have been proposed. The unifying factor in determining toxicity and carcinogenicity for all these metals is the generation of reactive oxygen and nitrogen species. Common mechanisms involving the Fenton reaction, generation of the superoxide radical and the hydroxyl radical appear to be involved for iron, copper, chromium, vanadium and cobalt primarily associated with mitochondria, microsomes and peroxisomes. However, a recent discovery that the upper limit of "free pools" of copper is far less than a single atom per cell casts serious doubt on the in vivo role of copper in Fenton-like generation of free radicals. Nitric oxide (NO) seems to be involved in arsenite-induced DNA damage and pyrimidine excision inhibition. Various studies have confirmed that metals activate signalling pathways and the carcinogenic effect of metals has been related to activation of mainly redox-sensitive transcription factors, involving NF-kappaB, AP-1 and p53. Antioxidants (both enzymatic and non-enzymatic) provide protection against deleterious metal-mediated free radical attacks. Vitamin E and melatonin can prevent the majority of metal-mediated (iron, copper, cadmium) damage both in vitro systems and in metal-loaded animals. Toxicity studies involving chromium have shown that the protective effect of vitamin E against lipid peroxidation may be associated rather with the level of non-enzymatic antioxidants than the activity of enzymatic antioxidants. However, a very recent epidemiological study has shown that a daily intake of vitamin E of more than 400 IU increases the risk of death and should be avoided. While previous studies have proposed a deleterious pro-oxidant effect of vitamin C (ascorbate) in the presence of iron (or copper), recent results have shown that even in the presence of redox-active iron (or copper) and hydrogen peroxide, ascorbate acts as an antioxidant that prevents lipid peroxidation and does not promote protein oxidation in humans in vitro. Experimental results have also shown a link between vanadium and oxidative stress in the etiology of diabetes. The impact of zinc (Zn) on the immune system, the ability of zinc to act as an antioxidant in order to reduce oxidative stress and the neuroprotective and neurodegenerative role of zinc (and copper) in the etiology of Alzheimer's disease is also discussed. This review summarizes recent findings in the metal-induced formation of free radicals and the role of oxidative stress in the carcinogenicity and toxicity of metals.

Mechanisms of Chemical Modulation and Toxicity of the Immune System

DTIC Science & Technology

1989-12-15

antigens and suppressor/cytotoxic cells bearing Lyt-2 surface antigens. Autoimmune or immunodeficient diseases have been characte.ized by alterations...Written Publication (cumulative list) A. Suppression of mitogen-induced blastogenesis of feline lymphocytes by in Yi incubation with carcinogenic

TREATMENT OF PAHS AND PCBS USING SULFATE RADICAL-BASED OXIDATION PROCESSES

EPA Science Inventory

Polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) in aquatic systems pose serious threat to public health due to their toxicity and potential carcinogenicity [1]. Sulfate radical-based oxidation processes can be effectively used for degradation of these...

NIEHS' David Rall

ERIC Educational Resources Information Center

Environmental Science and Technology, 1974

1974-01-01

According to Rall, director of NIEHS, the agency is supporting environmental research in the areas of occupational health, epidemiological, carcinogenic and biochemical toxicology, air pollution, food additives and nutrition. Rall's concern is that environmentalists have become sidetracked by the problems of esthetics and wildlife toxicity and…

Tracking the pathway of arsenic metabolism

EPA Science Inventory

Although the toxic and carcinogenic properties of arsenic have been recognized for centuries, only in the past few decades has research focused on understanding the metabolic fate of arsenic in humans and relating metabolism to adverse health effects. In humans, conversion of in...

SEMINAR PUBLICATION: ORGANIC AIR EMISSIONS FROM WASTE MANAGEMENT FACILITIES

EPA Science Inventory

The organic chemicals contained in wastes processed during waste management operations can volatilize into the atmosphere and cause toxic or carcinogenic effects or contribute to ozone formation. Because air emissions from waste management operations pose a threat to human health...

PHARMACEUTICALS AND PERSONAL CARE PRODUCTS IN THE ENVIRONMENT: AGENTS OF SUBTLE CHANGE?

EPA Science Inventory

During the last three decades, the impact of chemical pollution has focused almost exclusively on the conventional "priority" pollutants, especially those acutely toxic/carcinogenic pesticides and industrial intermediates displaying persistence in the environment. This spectrum o...

FORMATION AND ENANTIOSELECTIVE BIODEGRADATION OF THE ENANTIOMERS OF BROMOCHLOROACETIC ACID

EPA Science Inventory

Bromochloroacetic acid (BCAA) is formed by chlorination of drinking waters containing naturally occurring bromide. This haloacetic acid is a concern to public health because of suspected carcinogenicity and toxicity, and is a potential target of disinfectant byproduct regulations...

Do 16 Polycyclic Aromatic Hydrocarbons Represent PAH Air Toxicity?

PubMed Central

Samburova, Vera; Zielinska, Barbara; Khlystov, Andrey

2017-01-01

Estimation of carcinogenic potency based on analysis of 16 polycyclic aromatic hydrocarbons (PAHs) ranked by U.S. Environmental Protection Agency (EPA) is the most popular approach within scientific and environmental air quality management communities. The majority of PAH monitoring projects have been focused on particle-bound PAHs, ignoring the contribution of gas-phase PAHs to the toxicity of PAH mixtures in air samples. In this study, we analyzed the results of 13 projects in which 88 PAHs in both gas and particle phases were collected from different sources (biomass burning, mining operation, and vehicle emissions), as well as in urban air. The aim was to investigate whether 16 particle-bound U.S. EPA priority PAHs adequately represented health risks of inhalation exposure to atmospheric PAH mixtures. PAH concentrations were converted to benzo(a)pyrene-equivalent (BaPeq) toxicity using the toxic equivalency factor (TEF) approach. TEFs of PAH compounds for which such data is not available were estimated using TEFs of close isomers. Total BaPeq toxicities (∑88BaPeq) of gas- and particle-phase PAHs were compared with BaPeq toxicities calculated for the 16 particle-phase EPA PAH (∑16EPABaPeq). The results showed that 16 EPA particle-bound PAHs underrepresented the carcinogenic potency on average by 85.6% relative to the total (gas and particle) BaPeq toxicity of 88 PAHs. Gas-phase PAHs, like methylnaphthalenes, may contribute up to 30% of ∑88BaPeq. Accounting for other individual non-EPA PAHs (i.e., benzo(e)pyrene) and gas-phase PAHs (i.e., naphthalene, 1- and 2-methylnaphthalene) will make the risk assessment of PAH-containing air samples significantly more accurate. PMID:29051449

Comparative Analysis of the Relationship between Trichloroethylene Metabolism and Tissue-Specific Toxicity among Inbred Mouse Strains: Kidney Effects

PubMed Central

Yoo, Hong Sik; Bradford, Blair U.; Kosyk, Oksana; Uehara, Takeki; Shymonyak, Svitlana; Collins, Leonard B.; Bodnar, Wanda M.; Ball, Louise M.; Gold, Avram; Rusyn, Ivan

2014-01-01

Trichloroethylene (TCE) is a well-known environmental and occupational toxicant that is classified as carcinogenic to humans based on the epidemiological evidence of an association with higher risk of renal cell carcinoma. A number of scientific issues critical for assessing human health risks from TCE remain unresolved, such as the amount of kidney-toxic glutathione conjugation metabolites formed, inter-species and -individual differences, and the mode of action for kidney carcinogenicity. We hypothesized that TCE metabolite levels in the kidney are associated with kidney-specific toxicity. Oral dosing with TCE was conducted in sub-acute (600 mg/kg/d; 5 days; 7 inbred mouse strains) and sub-chronic (100 or 400 mg/kg/d; 1, 2, or 4 weeks; 2 inbred mouse strains) designs. We evaluated the quantitative relationship between strain-, dose-, and time-dependent formation of TCE metabolites from cytochrome P450-mediated oxidation [trichloroacetic acid (TCA), dichloroacetic acid (DCA), and trichloroethanol] and glutathione conjugation [S-(1,2-dichlorovinyl)-L-cysteine and S-(1,2-dichlorovinyl)glutathione], and various kidney toxicity phenotypes. In sub-acute study, we observed inter-strain differences in TCE metabolite levels in the kidney. In addition, we found that in several strains kidney-specific effects of TCE included induction of peroxisome proliferator-marker genes Cyp4a10 and Acox1, increased cell proliferation, and expression of KIM-1, a marker of tubular damage and regeneration. In sub-chronic study, peroxisome proliferator-marker gene induction and kidney toxicity diminished while cell proliferative response was elevated in a dose-dependent manner in NZW/LacJ, but not C57BL/6J mice. Overall, we show that TCE metabolite levels in the kidney are associated with kidney-specific toxicity and that these effects are strain-dependent. PMID:25424545

Do 16 Polycyclic Aromatic Hydrocarbons Represent PAH Air Toxicity?

PubMed

Samburova, Vera; Zielinska, Barbara; Khlystov, Andrey

2017-08-15

Estimation of carcinogenic potency based on analysis of 16 polycyclic aromatic hydrocarbons (PAHs) ranked by U.S. Environmental Protection Agency (EPA) is the most popular approach within scientific and environmental air quality management communities. The majority of PAH monitoring projects have been focused on particle-bound PAHs, ignoring the contribution of gas-phase PAHs to the toxicity of PAH mixtures in air samples. In this study, we analyzed the results of 13 projects in which 88 PAHs in both gas and particle phases were collected from different sources (biomass burning, mining operation, and vehicle emissions), as well as in urban air. The aim was to investigate whether 16 particle-bound U.S. EPA priority PAHs adequately represented health risks of inhalation exposure to atmospheric PAH mixtures. PAH concentrations were converted to benzo(a)pyrene-equivalent (BaPeq) toxicity using the toxic equivalency factor (TEF) approach. TEFs of PAH compounds for which such data is not available were estimated using TEFs of close isomers. Total BaPeq toxicities (∑ 88 BaPeq) of gas- and particle-phase PAHs were compared with BaPeq toxicities calculated for the 16 particle-phase EPA PAH (∑ 16EPA BaPeq). The results showed that 16 EPA particle-bound PAHs underrepresented the carcinogenic potency on average by 85.6% relative to the total (gas and particle) BaPeq toxicity of 88 PAHs. Gas-phase PAHs, like methylnaphthalenes, may contribute up to 30% of ∑ 88 BaPeq. Accounting for other individual non-EPA PAHs (i.e., benzo(e)pyrene) and gas-phase PAHs (i.e., naphthalene, 1- and 2-methylnaphthalene) will make the risk assessment of PAH-containing air samples significantly more accurate.

Interactive effects of inflammatory cytokine and abundant low-molecular-weight PAHs on inhibition of gap junctional intercellular communication, disruption of cell proliferation control, and the AhR-dependent transcription.

PubMed

Kabátková, Markéta; Svobodová, Jana; Pěnčíková, Kateřina; Mohatad, Dilshad Shaik; Šmerdová, Lenka; Kozubík, Alois; Machala, Miroslav; Vondráček, Jan

2015-01-05

Polycyclic aromatic hydrocarbons (PAHs) with lower molecular weight exhibit lesser genotoxicity and carcinogenicity than highly carcinogenic PAHs with a higher number of benzene rings. Nevertheless, they elicit specific effects linked with tumor promotion, such as acute inhibition of gap junctional intercellular communication (GJIC). Although inflammatory reaction may alter bioactivation and toxicity of carcinogenic PAHs, little is known about the impact of pro-inflammatory cytokines on toxic effects of the low-molecular-weight PAHs. Here, we investigated the impact of a pro-inflammatory cytokine, tumor necrosis factor-α (TNF-α), on the effects associated with tumor promotion and with induction of the aryl hydrocarbon receptor (AhR)-dependent gene expression in rat liver epithelial cells. We found that a prolonged incubation with TNF-α induced a down-regulation of GJIC, associated with reduced expression of connexin 43 (Cx43), a major connexin isoform found in liver epithelial cells. The Cx43 down-regulation was partly mediated by the activity of the mitogen-activated protein (MAP) p38 kinase. Independently of GJIC modulation, or p38 activation, TNF-α potentiated the AhR-dependent proliferative effect of a model low-molecular-weight PAH, fluoranthene, on contact-inhibited cells. In contrast, this pro-inflammatory cytokine repressed the fluoranthene-induced expression of a majority of model AhR gene targets, such as Cyp1a1, Ahrr or Tiparp. The results of the present study indicate that inflammatory reaction may differentially modulate various toxic effects of low-molecular-weight PAHs; the exposure to pro-inflammatory cytokines may both strengthen (inhibition of GJIC, disruption of contact inhibition) and repress (expression of a majority of AhR-dependent genes) their impact on toxic endpoints associated with carcinogenesis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Determination of the Chronic Mammalian Toxicological Effects of TNT (twenty-Four Month Chronic Toxicity/Carcinogenicity Study of Trinitrotoluene (TNT) in the B6C3F1 Hybrid Mouse). Volume 1

DTIC Science & Technology

1984-12-01

chemistry parameters (see section l1.D.) Results of pretreatment health screen were within limits for the mice of this strain and age. Microbiological ...negative as measured by Microbiological Associates, Bethesda MD. Animals received 5002 rodent chow from arrival urtil their termina~lon, except during a...CARCINOGENICITY STUDY OF FRINITROTOLUENE IN THE B6C3FI MOUSE. ’EST DIET CONCENTRATION OF TNT TESI DOSE % % A x 100 - K!E!Th (mg,/kg/day) SEX INTENDED ANALYSED REL

Long-term chemical carcinogenesis experiments for identifying potential human cancer hazards: collective database of the National Cancer Institute and National Toxicology Program (1976-1991).

PubMed Central

Huff, J; Haseman, J

1991-01-01

The carcinogenicity database used for this paper originated in the late 1960s by the National Cancer Institute (NCI) and since 1978 has been continued and made more comprehensive by the National Toxicology Program (NTP). The extensive files contain, among other sets of information, detailed pathology data on more than 400 long-term (most often 24-month) chemical carcinogenesis studies, comprising nearly 1600 individual experiments having at least 10 million tissue sections that have been evaluated for toxicity and carcinogenicity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1820269

Evidence for toxicity differences between inorganic arsenite and thioarsenicals in human bladder cancer cells.

PubMed

Naranmandura, Hua; Ogra, Yasumitsu; Iwata, Katsuya; Lee, Jane; Suzuki, Kazuo T; Weinfeld, Michael; Le, X Chris

2009-07-15

Arsenic toxicity is dependent on its chemical species. In humans, the bladder is one of the primary target organs for arsenic-induced carcinogenicity. However, little is known about the mechanisms underlying arsenic-induced carcinogenicity, and what arsenic species are responsible for this carcinogenicity. The present study aimed at comparing the toxic effect of DMMTA(V) with that of inorganic arsenite (iAs(III)) on cell viability, uptake efficiency and production of reactive oxygen species (ROS) toward human bladder cancer EJ-1 cells. The results were compared with those of a previous study using human epidermoid carcinoma A431 cells. Although iAs(III) was known to be toxic to most cells, here we show that iAs(III) (LC(50)=112 microM) was much less cytotoxic than DMMTA(V) (LC(50)=16.7 microM) in human bladder EJ-1 cells. Interestingly, pentavalent sulfur-containing DMMTA(V) generated a high level of intracellular ROS in EJ-1 cells. However, this was not observed in the cells exposed to trivalent inorganic iAs(III) at their respective LC(50) dose. Furthermore, the presence of N-acetyl-cysteine completely inhibited the cytotoxicity of DMMTA(V) but not iAs(III), suggesting that production of ROS was the main cause of cell death from exposure to DMMTA(V), but not iAs(III). Because the cellular uptake of iAs(III) is mediated by aquaporin proteins, and because the resistance of cells to arsenite can be influenced by lower arsenic uptake due to lower expression of aquaporin proteins (AQP 3, 7 and 9), the expression of several members of the aquaporin family was also examined. In human bladder EJ-1 cells, mRNA/proteins of AQP3, 7 and 9 were not detected by reverse transcription polymerase chain reaction (RT-PCR)/western blotting. In A431 cells, only mRNA and protein of AQP3 were detected. The large difference in toxicity between the two cell lines could be related to their differences in uptake of arsenic species.

Minerals, Tobacco and Smoking-Related Disease

NASA Astrophysics Data System (ADS)

Stephens, W. E.

2003-12-01

As much as 8% (by dry weight) of commercial tobacco is mineral, and the view that minerals are inert, playing no more than a passive role in smoking-related disease, is challenged. An inventory of minerals in tobacco is presented and an interpretation of their sources given. Using elemental abundances the relative contributions of natural and anthropogenic sources to the commercial product is quantitatively modelled relative to average crustal abundances. A framework is presented for investigating the potential ways in which minerals with, or acquire, toxic properties behave in the smoking environment. In order to represent a potential hazard any mineral (or mineral reaction product) with suspected toxic properties must partition into smoke and be respirable. For inhalation a significant proportion of the particles must be smaller than 10 microns. Three categories of potential hazard are recognised: 1. Minerals with intrinsic toxic properties. Quartz can amount to 1% or more in some cigarettes and is defined as a human carcinogen by the IARC. It is not likely to represent a hazard as its grain size is probably too coarse to be respirable. However talc, also a Type 1 carcinogen when it is contaminated with asbestos, is a common constituent of cigarette paper and may be of respirable size. Some other minerals also fall into this category. 2. Minerals that generate toxic products on combustion. Examples are the biominerals calcium oxalate monohydrate (whewellite) and dihydrate (weddellite), which amount to about 5 wt% of popular UK brands. These minerals decompose at tobacco combustion temperatures yielding large quantities of carbon monoxide. A substantial fraction of the CO budget of UK cigarettes may derive from this source. 3. Minerals that acquire toxic properties on combustion. Little is known about free radical generation on mineral surfaces during tobacco combustion, but the devolatilisation of calcic phases (carbonates and oxalates) creates oxide particles with surfaces highly adsorbent to polycyclic aromatic hydrocarbons (PAH). Calcic mineral particles are two orders of magnitude more abundant in smokers' lungs compared with non-smoking controls in residents of Vancouver. Such particles may thus be potential agents for the delivery of PAH carcinogens, including benzo(a)pyrene, to the lungs. None of the potential hazards listed above has yet been properly evaluated.

Detection of genotoxic and non-genotoxic carcinogens in Xpc(-/-)p53(+/-) mice.

PubMed

Melis, Joost P M; Speksnijder, Ewoud N; Kuiper, Raoul V; Salvatori, Daniela C F; Schaap, Mirjam M; Maas, Saskia; Robinson, Joke; Verhoef, Aart; van Benthem, Jan; Luijten, Mirjam; van Steeg, Harry

2013-01-15

An accurate assessment of the carcinogenic potential of chemicals and pharmaceutical drugs is essential to protect humans and the environment. Therefore, substances are extensively tested before they are marketed to the public. Currently, the rodent two-year bioassay is still routinely used to assess the carcinogenic potential of substances. However, over time it has become clear that this assay yields false positive results and also has several economic and ethical drawbacks including the use of large numbers of animals, the long duration, and the high cost. The need for a suitable alternative assay is therefore high. Previously, we have proposed the Xpa*p53 mouse model as a very suitable alternative to the two-year bioassay. We now show that the Xpc*p53 mouse model preserves all the beneficial traits of the Xpa*p53 model for sub-chronic carcinogen identification and can identify both genotoxic and non-genotoxic carcinogens. Moreover, Xpc*p53 mice appear to be more responsive than Xpa*p53 mice towards several genotoxic and non-genotoxic carcinogens. Furthermore, Xpc*p53 mice are far less sensitive than Xpa*p53 mice for the toxic activity of DNA damaging agents and as such clearly respond in a similar way as wild type mice do. These advantageous traits of the Xpc*p53 model make it a better alternative for in vivo carcinogen testing than Xpa*p53. This pilot study suggests that Xpc*p53 mice are suited for routine sub-chronic testing of both genotoxic and non-genotoxic carcinogens and as such represent a suitable alternative to possibly replace the murine life time cancer bioassay. Copyright © 2012 Elsevier Inc. All rights reserved.

The toxic chemistry of methyl bromide.

PubMed

Bulathsinghala, A T; Shaw, I C

2014-01-01

Methyl bromide (MeBr) is a chemically reactive compound that has found use as a fire retardant and fumigant used for wood, soil, fruits and grains. Its use is banned in many countries because of its ozone-depleting properties. Despite this ban, the use of MeBr persists in some parts of the world (e.g. New Zealand) due to its important role in maintaining strict biosecurity of exported and imported products. Its high chemical reactivity leads to a broad toxicological profile ranging from acute respiratory toxicity following inhalation exposure, through carcinogenicity to neurotoxicty. In this article, we discuss the chemistry of MeBr in the context of its mechanisms of toxicity. The chemical reactivity of MeBr clearly underlies its toxicity. Bromine (Br) is electronegative and a good leaving group; the δ+ carbon thus facilitates electrophilic methylation of biological molecules including glutathione (GSH) via its δ- sulphur atom, leading to downstream effects due to GSH depletion. DNA alkylation, either directly by MeBr or indirectly due to reduction in GSH-mediated detoxification of reactive alkylating chemical species, might explain the carcinogenicity of MeBr. The neurotoxicity of MeBr is much more difficult to understand, but we speculate that methyl phosphates formed in cells might contribute to its neurone-specific toxicity via cholinesterase inhibition. Finally, evidence reviewed shows that it is unlikely for Br⁻ liberated by the metabolism of MeBr to have any toxicological effect because the Br⁻ dose is very low.

Supplement to the Carcinogenic Potency Database (CPDB): results of animal bioassays published in the general literature in 1993 to 1994 and by the National Toxicology Program in 1995 to 1996.

PubMed Central

Gold, L S; Manley, N B; Slone, T H; Rohrbach, L

1999-01-01

The Carcinogenic Potency Database (CPDB) is a systematic and unifying analysis of results of chronic, long-term cancer tests. This paper presents a supplemental plot of the CPDB, including 513 experiments on 157 test compounds published in the general literature in 1993 and 1994 and in Technical Reports of the National Toxicology Program in 1995 and 1996. The plot standardizes the experimental results (whether positive or negative for carcinogenicity), including qualitative data on strain, sex, route of compound administration, target organ, histopathology, and author's opinion and reference to the published paper, as well as quantitative data on carcinogenic potency, statistical significance, tumor incidence, dose-response curve shape, length of experiment, duration of dosing, and dose rate. A numerical description of carcinogenic potency, the TD(subscript)50(/subscript), is estimated for each set of tumor incidence data reported. When added to the data published earlier, the CPDB now includes results of 5,620 experiments on 1,372 chemicals that have been reported in 1,250 published papers and 414 National Cancer Institute/National Toxicology Program Technical Reports. The plot presented here includes detailed analyses of 25 chemicals tested in monkeys for up to 32 years by the National Cancer Institute. Half the rodent carcinogens that were tested in monkeys were not carcinogenic, despite usually strong evidence of carcinogenicity in rodents and/or humans. Our analysis of possible explanatory factors indicates that this result is due in part to the fact that the monkey studies lacked power to detect an effect compared to standard rodent bioassays. Factors that contributed to the lack of power are the small number of animals on test; a stop-exposure protocol for model rodent carcinogens; in a few cases, toxic doses that resulted in stoppage of dosing or termination of the experiment; and in a few cases, low doses administered to monkeys or early termination of the experiment even though the doses were not toxic. Among chemicals carcinogenic in both monkeys and rodents, there is some support for target site concordance, but it is primarily restricted to liver tumors. Potency values are highly correlated between rodents and monkeys. The plot in this paper can be used in conjunction with the earlier results published in the CRC Handbook of Carcinogenic Potency and Genotoxicity Databases [Gold LS, Zeiger E, eds. Boca Raton FL:CRC Press, 1997] and with our web site (http://potency.berkeley.edu), which includes a guide to the plot of the database, a complete description of the numerical index of carcinogenic potency (TD50), and a discussion of the sources of data, the rationale for the inclusion of particular experiments and particular target sites, and the conventions adopted in summarizing the literature. Two summary tables permit easy access to the literature of animal cancer tests by target organ and by chemical. For readers using the CPDB extensively, a combined plot on diskette or other format is available from the first author. It includes all results published earlier and in this paper, ordered alphabetically by chemical. A SAS database is also available. PMID:10421768

Dehydropyrrolizidine Alkaloid Toxicity, Cytotoxicity, and Carcinogenicity

PubMed Central

Stegelmeier, Bryan L.; Colegate, Steven M.; Brown, Ammon W.

2016-01-01

Dehydropyrrolizidine alkaloid (DHPA)-producing plants have a worldwide distribution amongst flowering plants and commonly cause poisoning of livestock, wildlife, and humans. Previous work has produced considerable understanding of DHPA metabolism, toxicity, species susceptibility, conditions, and routes of exposure, and pathogenesis of acute poisoning. Intoxication is generally caused by contaminated grains, feed, flour, and breads that result in acute, high-dose, short-duration poisoning. Acute poisoning produces hepatic necrosis that is usually confirmed histologically, epidemiologically, and chemically. Less is known about chronic poisoning that may result when plant populations are sporadic, used as tisanes or herbal preparations, or when DHPAs contaminate milk, honey, pollen, or other animal-derived products. Such subclinical exposures may contribute to the development of chronic disease in humans or may be cumulative and probably slowly progress until liver failure. Recent work using rodent models suggest increased neoplastic incidence even with very low DHPA doses of short durations. These concerns have moved some governments to prohibit or limit human exposure to DHPAs. The purpose of this review is to summarize some recent DHPA research, including in vitro and in vivo DHPA toxicity and carcinogenicity reports, and the implications of these findings with respect to diagnosis and prognosis for human and animal health. PMID:27916846

Human health risk assessment of chloroxylenol in liquid hand soap and dishwashing soap used by consumers and health-care professionals.

PubMed

Yost, Lisa J; Rodricks, Joseph D; Turnbull, Duncan; DeLeo, Paul C; Nash, J Frank; Quiñones-Rivera, Antonio; Carlson, Pete A

2016-10-01

A quantitative human risk assessment of chloroxylenol was conducted for liquid hand and dishwashing soap products used by consumers and health-care workers. The toxicological data for chloroxylenol indicate lack of genotoxicity, no evidence of carcinogenicity, and minimal systemic toxicity. No observed adverse effect levels (NOAEL) were established from chronic toxicity studies, specifically a carcinogenicity study that found no cancer excess (18 mg/kg-day) and studies of developmental and reproductive toxicity (100 mg/kg-day). Exposure to chloroxylenol for adults and children was estimated for two types of rinse-off cleaning products, one liquid hand soap, and two dishwashing products. The identified NOAELs were used together with exposure estimates to derive margin of exposure (MOE) estimates for chloroxylenol (i.e., estimates of exposure over NOAELs). These estimates were designed with conservative assumptions and likely overestimate exposure and risk (i.e., highest frequency, 100% dermal penetration). The resulting MOEs ranged from 178 to over 100, 000, 000 indicating negligibly small potential for harm related to consumer or health-care worker exposure to chloroxylenol in liquid soaps used in dish washing and hand washing. Copyright © 2016 Elsevier Inc. All rights reserved.

75 FR 51968 - Outer Continental Shelf Air Regulations Consistency Update for Massachusetts

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-24

... comments to: Ida McDonnell, Air Permits, Toxics and Indoor Air Unit, Office of Ecosystem Protection, U.S... INFORMATION CONTACT: Ida E. McDonnell, Air Permits, Toxics and Indoor Air Unit, U.S. Environmental Protection... Continental Shelf Air Regulations Consistency Update for Massachusetts AGENCY: Environmental Protection Agency...

76 FR 77703 - Hexythiazox; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-14

... the relationship of the results of the studies to human risk. EPA has also considered available... effects including potential carcinogenicity of hexythiazox. Specific information on the studies received...-level (NOAEL) and the lowest-observed-adverse-effect- level (LOAEL) from the toxicity studies can be...

78 FR 64228 - National Institutes of Health

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-28

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Environmental Health Sciences; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... Health Sciences Special Emphasis Panel Assessment of Toxic and Carcinogenic Effects from Exposure to...

Health Effects Assessment for Acenaphthene

EPA Science Inventory

Because of the lack of data for the carcinogenicity and threshold toxicity of acenaphthene risk assessment values cannot be derived. The ambient water quality criterion of 0.2 mg/l is based on organoleptic data, which has no known relationship to potential human health effects. A...

Current status of genomics research on mycotoxigenic fungi

USDA-ARS?s Scientific Manuscript database

Mold-produced secondary metabolites that are toxic and carcinogenic are termed mycotoxins. They are biosynthesized in a number of fungi, mainly from species in the Aspergillus, Fusarium and Penicillium genera. Mycotoxins contaminate agricultural commodities such as grains, fruits and nuts. Due to th...

Formation of Nitrosamines in Food and in the Digestive System

ERIC Educational Resources Information Center

Wishnok, John S.

1977-01-01

A discussion is presented of the toxicity, chemistry, and environmental presence of nitrosamines. Carcinogenicity and effects on various organs of test animals are reviewed. Also some information on the presence of use of nitrosamines in human food is given. (MR)

In vitro cytotoxicity of various dehydropyrrolizidine ester alkaloids

USDA-ARS?s Scientific Manuscript database

Dehydropyrrolizidine alkaloids (DHPAs) are plant-derived hepato-, pneumo- and geno-toxins that are carcinogenic in several species. Because of the difficulty in isolating sufficient DHPA for toxicological studies, there are few direct comparisons of toxicity. The objectives of this study was to de...

ARSENIC IN DRINKING WATER: EPIDEMIOOOGIC STUDIES OF LOW EXPOSURE IN THE UNITED STATES

EPA Science Inventory

Because there is no animal model fully adequate to study the mechanisms of arsenic toxicity and carcinogenicity; human epidemiological studies incorporating sensitive biomarkers for assessing exposure, cancer, noncancer effects and susceptibility of arsenic are needed to evalua...

BIOMARKERS OF EXPOSURE: A CASE STUDY WITH INORGANIC ARSENIC

EPA Science Inventory

Inorganic arsenic (iAs) is a human toxicant and carcinogen that is found in the environment as a natural contaminant and from anthropogenic sources. Most mammalian species metabolize iAs by reduction to trivalent species followed by oxidative methylation to pentavalent species. ...

Incidences and range of spontaneous findings in the lymphoid and haemopoietic system of control Charles River CD-1 mice (Crl: CD-1(ICR) BR) used in chronic toxicity studies.

PubMed

Bradley, Alys; Mukaratirwa, Sydney; Petersen-Jones, Morven

2012-01-01

The authors performed a retrospective study to determine the incidences and range of spontaneous pathology findings in the lymphoid and haemopoietic systems of control Charles River CD-1 mice (Crl: CD-1(ICR) BR). Data was collected from 2,560 mice from control dose groups (104-week and 80-week carcinogenicity studies; 13-week studies), from regulatory studies evaluated at the authors' laboratory between 2005 and 2010. Lesions of the lymphoid and hematopoietic systems were uncommon in 13-week studies but were of high incidence in the carcinogenicity studies (80- or 104-week duration). The most common finding overall was lymphoid hyperplasia within the spleen, thymus, and lymph nodes. The finding of benign lymphoid hyperplasia of the thymus is unusual in other mouse strains. The most common cause of death in the carcinogenicity studies was lymphoma. It is hoped that the results presented here will provide a useful database of incidental pathology findings in CD-1 mice on carcinogenicity studies.

METABOLISM, GENOTOXICITY, AND CARCINOGENICITY OF COMFREY

PubMed Central

Mei, Nan; Guo, Lei; Fu, Peter P.; Fuscoe, James C.; Luan, Yang; Chen, Tao

2018-01-01

Comfrey has been consumed by humans as a vegetable and a tea and used as an herbal medicine for more than 2000 years. Comfrey, however, produces hepatotoxicity in livestock and humans and carcinogenicity in experimental animals. Comfrey contains as many as 14 pyrrolizidine alkaloids (PA), including 7-acetylintermedine, 7-acetyllycopsamine, echimidine, intermedine, lasiocarpine, lycopsamine, myoscorpine, symlandine, symphytine, and symviridine. The mechanisms underlying comfrey-induced genotoxicity and carcinogenicity are still not fully understood. The available evidence suggests that the active metabolites of PA in comfrey interact with DNA in liver endothelial cells and hepatocytes, resulting in DNA damage, mutation induction, and cancer development. Genotoxicities attributed to comfrey and riddelliine (a representative genotoxic PA and a proven rodent mutagen and carcinogen) are discussed in this review. Both of these compounds induced similar profiles of 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived DNA adducts and similar mutation spectra. Further, the two agents share common mechanisms of drug metabolism and carcinogenesis. Overall, comfrey is mutagenic in liver, and PA contained in comfrey appear to be responsible for comfrey-induced toxicity and tumor induction. PMID:21170807

Chromium carcinogenicity: California strategies.

PubMed

Alexeeff, G V; Satin, K; Painter, P; Zeise, L; Popejoy, C; Murchison, G

1989-10-01

Hexavalent chromium was identified by California as a toxic air contaminant (TAC) in January 1986. The California Department of Health Services (CDHS) concurred with the findings of the International Agency for Research on Cancer that there is sufficient evidence to demonstrate the carcinogenicity of chromium in both animals and humans. CDHS did not find any compelling evidence demonstrating the existence of a threshold with respect to chromium carcinogenesis. Experimental data was judged inadequate to assess potential human reproductive risks from ambient exposures. Other health effects were not expected to occur at ambient levels. The theoretically increased lifetime carcinogenic risk from a continuous lifetime exposure to hexavalent chromium fell within the range 12-146 cancer cases per nanogram hexavalent chromium per cubic meter of air per million people exposed, depending on the potency estimate used. The primary sources found to contribute significantly to the risk of exposure were chrome platers, chromic acid anodizing facilities and cooling towers utilizing hexavalent chromium as a corrosion inhibitor. Evaluation of genotoxicity data, animal studies and epidemiological studies indicates that further consideration should be given to the potential carcinogenicity of hexavalent chromium via the oral route.

Polycyclic aromatic hydrocarbons in biomass-burning emissions and their contribution to light absorption and aerosol toxicity.

PubMed

Samburova, Vera; Connolly, Jessica; Gyawali, Madhu; Yatavelli, Reddy L N; Watts, Adam C; Chakrabarty, Rajan K; Zielinska, Barbara; Moosmüller, Hans; Khlystov, Andrey

2016-10-15

In recent years, brown carbon (BrC) has been shown to be an important contributor to light absorption by biomass-burning atmospheric aerosols in the blue and near-ultraviolet (UV) part of the solar spectrum. Emission factors and optical properties of 113 polycyclic aromatic hydrocarbons (PAHs) were determined for combustion of five globally important fuels: Alaskan, Siberian, and Florida swamp peat, cheatgrass (Bromus tectorum), and ponderosa pine (Pinus ponderosa) needles. The emission factors of total analyzed PAHs were between 1.9±0.43.0±0.6 and 9.6±1.2-42.2±5.4mgPAHkg(-1)fuel for particle- and gas phase, respectively. Spectrophotometric analysis of the identified PAHs showed that perinaphthenone, methylpyrenes, and pyrene contributed the most to the total PAH light absorption with 17.2%, 3.3 to 10.5%, and 7.6% of the total particle-phase PAH absorptivity averaged over analyzed emissions from the fuels. In the gas phase, the top three PAH contributors to BrC were acenaphthylene (32.6%), anthracene (8.2%), and 2,4,5-trimethylnaphthalene (8.0%). Overall, the identified PAHs were responsible for 0.087-0.16% (0.13% on average) and 0.033-0.15% (0.11% on average) of the total light absorption by dichloromethane-acetone extracts of particle and gas emissions, respectively. Toxic equivalency factor (TEF) analysis of 16 PAHs prioritized by the United States Environmental Protection Agency (EPA) showed that benzo(a)pyrene contributed the most to the PAH carcinogenic potency of particle phase emissions (61.8-67.4% to the total carcinogenic potency of Σ16EPA PAHs), while naphthalene played the major role in carcinogenicity of the gas phase PAHs in the biomass-burning emission analyzed here (35.4-46.0% to the total carcinogenic potency of Σ16EPA PAHs). The 16 EPA-prioritized PAHs contributed only 22.1±6.2% to total particle and 23.4±11% to total gas phase PAH mass, thus toxic properties of biomass-burning PAH emissions are most likely underestimated. Copyright © 2016 Elsevier B.V. All rights reserved.

Enrichment, spatial distribution of potential ecological and human health risk assessment via toxic metals in soil and surface water ingestion in the vicinity of Sewakht mines, district Chitral, Northern Pakistan.

PubMed

Rehman, Inayat Ur; Ishaq, Muhammad; Ali, Liaqat; Khan, Sardar; Ahmad, Imtiaz; Din, Imran Ud; Ullah, Hameed

2018-06-15

This study focuses on enrichment, spatial distribution, potential ecological risk index (PERI) and human health risk of various toxic metals taken via soil and surface water in the vicinity of Sewakht mines, Pakistan. The samples of soils (n = 54) of different fields and surface water (n = 38) were analyzed for toxic metals including cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), manganese (Mn), lead (Pb), nickel (Ni), zinc (Zn) and molybdenum (Mo). Soil pollution level was evaluated using pollution indices including geo-accumulation index (Igeo), contamination factor (CF), degree of contamination (CD), enrichment factor (EF) and PERI. CF showed moderate contamination of soil with Cd, Co, Fe and Mo, while Igeo values indicated moderate accumulation of Cu. For Cd, EF> 1.5 was found in agricultural soils of the study area. PERI findings presented a very high ecological risk (PERI > 380) at two sites (4%), considerable ecological risk at four sites (7.4%). Non-carcinogenic risk from exposure to Fe in soil was higher than limit (HI > 1) for both children and adults. Moreover, carcinogenic risk postured by soil contaminants i.e. Cd, Cr, Co and Ni in children was higher than their limits (except Pb), while in adults only Co posed higher risk of cancer than the limit (10 -4 ) through soil exposure. Non-carcinogenic risks in children due to Cd, Co, Mo via surface water intake were higher than their safe limits (HQ > 1), while in adults the risk order was Cr > Cd > Cu > Pb > Co > Mo. Moreover, carcinogenic risk exposure due to Co > Cd > Cr > Ni from surface water (except Pb) was higher than the tolerable limit (1 × 10 -4 ) both for children and adults. However, Pb concentrations in both soil and surface water exposure were not likely to cause cancer risk in the local population. Copyright © 2018 Elsevier Inc. All rights reserved.

Pyrrolizidine alkaloid-containing toxic plants (Senecio, Crotalaria, Cynoglossum, Amsinckia, Heliotropium, and Echium spp.).

PubMed

Stegelmeier, Bryan L

2011-07-01

Pyrrolizidine alkaloid (PA)-containing plants are found throughout the world and are probably the most common plant cause of poisoning of livestock, wildlife, and humans. PAs are potent liver toxins that under some conditions can be carcinogenic. This article briefly introduces high-risk North American PA-containing plants, summarizing their toxicity and subsequent pathology. Current diagnostic techniques, treatments, and strategies to avoid losses to PA poisoning are also reviewed. Published by Elsevier Inc.

Carcinogenicity and Immunotoxicity of Embedded Depleted Uranium and Heavy-Metal Tungsten Alloy in Rodents

DTIC Science & Technology

2006-10-01

local metal- induced toxicity daily for two weeks following surgery and weekly thereafter for the duration of the study. Task 1 - Determine whether...A quick and simple method for the quantitation of lactate dehydrogenase release in measurements of cellular cytotoxicity and tumor necrosis factor...4 months, no signs of local or systemic toxic- ity were observed (Peuster et al. 2003). Studies on health effects of Ni and Co are more numerous

Characterization of the chemicals used in hydraulic fracturing fluids for wells located in the Marcellus Shale Play.

PubMed

Chen, Huan; Carter, Kimberly E

2017-09-15

Hydraulic fracturing, coupled with the advances in horizontal drilling, has been used for recovering oil and natural gas from shale formations and has aided in increasing the production of these energy resources. The large volumes of hydraulic fracturing fluids used in this technology contain chemical additives, which may be toxic organics or produce toxic degradation byproducts. This paper investigated the chemicals introduced into the hydraulic fracturing fluids for completed wells located in Pennsylvania and West Virginia from data provided by the well operators. The results showed a total of 5071 wells, with average water volumes of 5,383,743 ± 2,789,077 gal (mean ± standard deviation). A total of 517 chemicals was introduced into the formulated hydraulic fracturing fluids. Of the 517 chemicals listed by the operators, 96 were inorganic compounds, 358 chemicals were organic species, and the remaining 63 cannot be identified. Many toxic organics were used in the hydraulic fracturing fluids. Some of them are carcinogenic, including formaldehyde, naphthalene, and acrylamide. The degradation of alkylphenol ethoxylates would produce more toxic, persistent, and estrogenic intermediates. Acrylamide monomer as a primary degradation intermediate of polyacrylamides is carcinogenic. Most of the chemicals appearing in the hydraulic fracturing fluids can be removed when adopting the appropriate treatments. Copyright © 2017 Elsevier Ltd. All rights reserved.

Risks associated with consumption of herbal teas.

PubMed

Manteiga, R; Park, D L; Ali, S S

1997-01-01

Plants have been used for medicinal purposes for centuries. Health-oriented individuals are turning to herbal teas as alternatives to caffeinated beverages such as coffee, tea, and cocoa and for low-caloric supplements. The popularity of herbal tea consumption has increased significantly during the past two decades in the U.S. Hundreds of different teas made up of varied mixtures of roots, leaves, seeds, barks, or other parts of shrubs, vines, or trees are sold in health food stores. Although chemists have been characterizing toxic plant constituents for over 100 years, toxicological studies of herbal teas have been limited and, therefore, the safety of many of these products is unknown. Plants synthesize secondary metabolites that are not essential in the production of energy and whose role may be in the defense mechanisms as plant toxins to their interactions with other plants, herbivores, and parasites. Pyrrolizidine alkaloids (PAs) were among the first naturally occurring carcinogens identified in plant products, and their presence in herbal teas is a matter of public health significance. Some herbal tea mixtures and single-ingredient herbal teas have been analyzed for toxic/mutagenic potential by bioassay and chromatographic techniques. Numerous human and animal intoxications have been associated with naturally occurring components, including pyrrolizidine alkaloids, tannins, and safrole. Thus, the prevention of human exposure to carcinogens or mutagens present in herbal tea mixture extracts is crucial. Preparation of infusion drinks prepared from plants appears to concentrate biologically active compounds and is a major source of PA poisoning. The quantity and consumption over a long period of time is of major concern. It is recommended that widespread consumption of herbal infusions should be minimized until data on the levels and varieties of carcinogens, mutagens, and toxicants are made available.

Toxicity and carcinogenicity studies of boric acid in male and female B6C3F1 mice.

PubMed Central

Dieter, M P

1994-01-01

Toxicity and potential carcinogenicity studies of boric acid were investigated in mice to verify in a second rodent species that this was a noncarcinogenic chemical. Earlier chronic studies in rats indicated boric acid was not a carcinogen. The chemical is nominated for testing because over 200 tons are produced annually, there are multiple uses for the product, and there is potential for widespread human exposure, both orally and dermally. Both sexes of B6C3F1 mice were offered diets mixed with boric acid for 14 days, 13 weeks, or 2 years. Dietary doses used in the acute, 14-day study were 0, 0.62, 1.25, 2.5, 5, and 10%; those in the subchronic, 13-week study were 0, 0.12, 0.25, 0.50, 1, and 2%; and doses in the 2-year, chronic study were 0, 0.25, and 0.50% in the diet. Mortality, clinical signs of toxicity, estimates of food consumption, body weight gain, and histopathologic examination of selected tissues constituted the variables measured. In the 14-day study mortality was proportional to dose and time of exposure in both sexes, occurring in dose groups as low as 2.5% and as early as 7 days of exposure. Body weights were depressed more than 10% below controls in the higher dose groups of both sexes. Mortality in the 13-week study was confined to the two highest dose groups in male mice and to the 2%-dose group in females. Body weight depression from 8 to 23% below those of controls occurred in the 0.50% and higher dose groups of both sexes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7889889

[REDUCTION OF THE CONTENT OF AFLATOXIN-FORMING FUNGI IN CONTAMINATED GRAINS BY METHODS OF HYDROTHERMAL TREATMENT].

PubMed

Shentsova, E S; Lytkina, L I; Shevtsov, A A

2015-01-01

Microscopic fungi affecting grain and products of its processing, under certain conditions, are capable of producing over 100 mycotoxins, some of which are carcinogenic. Mycotoxins are falled to the most dangerous contaminants of food and compound animal feedstuff, they possess toxicity, mutagenic and carcinogenic properties. The most toxic and dangerous carcinogens are aflatoxins which affect on virtually all cells of the body of the human and agricultural animals, provoking the occurrence of diseases--aflatoxicoses. Aflatoxins give rise to encephalopathy and fatty degeneration of internal organs. The World Health Organization mentions aflatoxins as a cause of the origin of cancer. Currently in Russia there is a real danger of the negative impact of mycotoxins on farm animals in feeding grain affected by aflatoxins. The gain in the number of aflatoxicoses is a serious hygienic problem. This is related with the wide spread of producers of aflatoxins in nature and also with the intensive trade of grain and products of its processing between countries, a lack of control over their content. Detoxification of the affected products is an actual task, because its use causes irreparable harm to human health andfarm animals. Currently there are known several ways of inactivation of aflatoxins in the grain, based on the use of hydrothermal treatment. IR heat treatment, ultraviolet irradiation and extrusion were established to be the most rational approaches, providing the reduction offungi in the grain of aflatoxin-forming fungi by 80 ... 100%, aflatoxin B1--by the 76... 100% and a decrease in the degree of toxicity by 2.3 times. There are presented experimental data of various ways of disinfecting grain and appropriateness of their application in practice.

Interaction between carcinogenic and anti-carcinogenic trace elements in the scalp hair samples of different types of Pakistani female cancer patients.

PubMed

Wadhwa, Sham Kumar; Kazi, Tasneem Gul; Afridi, Hassan Imran; Talpur, Farah Naz; Naeemullah

2015-01-15

It was investigated that carcinogenic processes are linked with the imbalances of essential trace and toxic elements in body fluid and tissues of human. In this study, the relationship between carcinogenic elements, arsenic (As), cadmium (Cd), and nickel (Ni), and anti-carcinogenic elements, selenium (Se) and zinc (Zn), in the scalp hair of different female cancer patients (breast, cervix, mouth and ovarian) was studied. The scalp hair samples were collected from cancer patients and referent female subjects of the same age group and socioeconomic status. The scalp hair samples were oxidized by 65% nitric acid and 30% hydrogen peroxide by microwave oven and analyzed by atomic absorption spectrometry. The validity and accuracy of the methodology were checked using certified reference material of human hair (BCR 397). The mean concentrations of As, Cd, and Ni were found to be significantly higher in the scalp hair samples of cancerous patients as compared to referents, while reverse results were obtained in the case of Zn and Se (p<0.01). The study revealed that low level of trace elements (Se, Zn) and high level of heavy elements (As, Cd, and Ni) were associated with increased risk of cancer. Copyright © 2014 Elsevier B.V. All rights reserved.

Inhibition of DNA synthesis by chemical carcinogens in cultures of initiated and normal proliferating rat hepatocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Novicki, D.L.; Rosenberg, M.R.; Michalopoulos, G.

1985-01-01

Rat hepatocytes in primary culture can be stimulated to replicate under the influence of rat serum and sparse plating conditions. Higher replication rates are induced by serum from two-thirds partially hepatectomized rats. The effects of carcinogens and noncarcinogens on the ability of hepatocytes to synthesize DNA were examined by measuring the incorporation of (3H)thymidine by liquid scintillation counting and autoradiography. Hepatocyte DNA synthesis was not decreased by ethanol or dimethyl sulfoxide at concentrations less than 0.5%. No effect was observed when 0.1 mM ketamine, Nembutal, hypoxanthine, sucrose, ascorbic acid, or benzo(e)pyrene was added to cultures of replicating hepatocytes. Estrogen, testosterone,more » tryptophan, and vitamin E inhibited DNA synthesis by approximately 50% at 0.1 mM, a concentration at which toxicity was noticeable. Several carcinogens requiring metabolic activation as well as the direct-acting carcinogen N-methyl-N'-nitro-N-nitrosoguanidine interfered with DNA synthesis. Aflatoxin B1 inhibited DNA synthesis by 50% (ID50) at concentrations between 1 X 10(-8) and 1 X 10(-7) M. The ID50 for 2-acetylaminofluorene was between 1 X 10(-7) and 1 X 10(-6) M. Benzo(a)pyrene and 3'-methyl-4-dimethylaminoazobenzene inhibited DNA synthesis 50% between 1 X 10(-5) and 1 X 10(-4) M. Diethylnitrosamine and dimethylnitrosamine (ID50 between 1 X 10(-4) and 5 X 10(-4) M) and 1- and 2-naphthylamine (ID50 between 1 X 10(-5) and 5 X 10(-4) M) caused inhibition of DNA synthesis at concentrations which overlapped with concentrations that caused measurable toxicity.« less

Source contributions to total concentrations and carcinogenic potencies of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) in ambient air: a case study in Suzhou City, China.

PubMed

Xuan, Zhiqiang; Bi, Chenglu; Li, Jiafu; Nie, Jihua; Chen, Zhihai

2017-10-01

The potential source categories and source contributions of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) in ambient air from Suzhou City, China, were performed by principal component analysis-multiple linear regression (PCA-MLR) and positive matrix factorization (PMF). The carcinogenic potencies of PCDD/Fs were quantitatively apportioned based on the positive matrix factorization-toxic equivalent concentration (PMF-TEQ) method. The results of the present study were summarized as follows. (1) The total concentrations and toxic equivalent concentrations of PCDD/Fs (∑PCDD/Fs and TEQ) in ambient air from Suzhou City were 1.34-42.80 pg N m -3 and 0.081-1.22 pg I-TEQ N m -3 , respectively. (2) PCA-MLR suggested that industrial combustion (IC), electric arc furnaces (EAFs) and secondary aluminum smelters (ALSs), unleaded gas-fueled vehicle sources (UGFVs), ALSs, and hazardous solid waste incinerators (HSWIs) could be the primary PCDD/F contributors, accounting for 13.2, 16.7, 35.5, 19.4, and 15.2% of ∑PCDD/Fs, respectively. (3) PMF and PMF-TEQ indicated that EAFs (carbon steel), UGFVs, IC, ALSs, municipal solid waste incinerators (MSWIs) and hospital waste incinerators (HWIs), and HSWIs contributed 10.9, 10.9, 42.8, 11.3, 10.7, and 13.4% to ∑PCDD/Fs, but contributed 8.3, 12.3, 50.3, 12.7, 6.0, and 10.4% to carcinogenic potencies of PCDD/Fs. This study was the first attempt to quantitatively apportion the source-specific carcinogenic potencies of PCDD/Fs in ambient air.

[COMPARATIVE ASSESSMENT OF THE MULTIMEDIA CANCER HEALTH RISKS CAUSED BY CONTAMINATION OF THE KRASNOIARSK KRAĬ REGIONS' ENVIRONMENT].

PubMed

Novikov, S M; Shashina, T A; Dodina, N S; Kislitsin, V A; Vorobieva, L M; Goriaev, D V; Tikhonova, I V; Kurkatov, S V

2015-01-01

Krasnoyarsk Krai is a region with developed mining and processing industries, notoriously known industries, as sources of carcinogenic emission. For 55 administrative units of the Krai 303 large enterprises' industrial emissions were preliminary prioritized and their location was designated. Only 52% out of the carcinogens emitted into the ambient air by industries were controlled, in other environments the figures ranged from 20% (soil, food) to 48% (drinking water), 10 carcinogens were not controlled in the environment at all. Based on the results of ranking carcinogenic emission and analysis of the carcinogens monitoring in the environment in 2007-2011 31 substances were selected. A comparative analysis of multiple environmental carcinogenic risks showed that 78% of the areas, based on the receipt ofcarcinogensfrom two media, and 80% ofthe areas taking into account the receipt ofcarcinogens from three media attributed to the alarming level of risk for population, that requires continuous monitoring and routine health interventions for its mitigation. The maximal multiple environmental risk values that took into account inputs from all sources were close to the upper boundary alarming level of risk, in Divnogorsk (7,80E-04), Norilsk (7,97 E-04), Krasnoyarsk (8,84E-04) and Achinsk (9,4 E-04). The greatest inputs to total individual cancer risk from polluted ambient air were made by benzene, chromium VI, formaldehyde and nickel, from drinking water--by arsenic, aldrin and heptachlor from soil--by arsenic and lead. The ambient air input into total multiple environmental carcinogenic risk ranged from 31.5 to 99.5%, drinking water input--from 0.5 to 68.5%, soil--up to 0.1%. Areas with maximum levels of total carcinogenic risk are characterized by the highest levels of average long-term indices of cancer development. The study discussed in this article has screening nature. Further in-depth researches for carcinogenic and toxic multimedia risks are required.

A TOXICITY ASSESSMENT APPROACH FOR EVALUATION OF IN-SITU BIOREMEDIATION OF PAH CONTAMINATED SEDIMENTS

EPA Science Inventory

Polycyclic aromatic hydrocarbons (PAHs) represent a group of organic contaminants known for their prevalence and persistence in petroleum-impacted environment such as groundwater, soils and sediments. Many high molecular weight PAHs are suspected carcinogens and the existence of...

CAPSULE REPORT: SOURCES AND AIR EMISSION CONTROL TECHNOLOGIES AT WASTE MANAGEMENT FACILITIES

EPA Science Inventory

The chemicals processed during waste management operations can volatilize into the atmosphere and cause carcinogenic or other toxic effects or contribute to ozone formation. Regulations have been developed to control air emissions from these operations. The EPA has promulgated st...

Field ecology, fungal sex and food contamination involving Aspergillus species

USDA-ARS?s Scientific Manuscript database

Several species within the genus Aspergillus are capable of producing a myriad of toxic secondary metabolites, with aflatoxin being of most concern. These fungi happen to colonize important agricultural commodities, thereby having the potential to contaminate our food with carcinogenic aflatoxins. P...

ARSENITE BINDING TO SYNTHETIC PEPTIDES: THE EFFECT OF INCREASING LENGTH BETWEEN TWO CYSTEINES

EPA Science Inventory

Binding of trivalent arsenicals to peptides and proteins can alter peptide/protein structure and enzyme function and thereby contribute to arsenic toxicity and carcinogenicity. We utilized radioactive 73As- labeled arsenite and vacuum filtration methodology to determine the bindi...

NORMAL GENE EXPRESSION IN MALE F344 RAT NASAL TRANSITIONAL/RESPIRATORY EPITHELIUM

EPA Science Inventory

Abstract

The nasal epithelium is an important target site for chemically-induced toxicity and carcinogenicity in rodents. Gene expression profiles were determined in order to provide normal baseline data for nasal transitional/respiratory epithelium from healthy rats. Ce...

NORMAL NASAL GENE EXPRESSION LEVELS USING CDNA ARRAY TECHNOLOGY

EPA Science Inventory

Normal Nasal Gene Expression Levels Using cDNA Array Technology.

The nasal epithelium is a target site for chemically-induced toxicity and carcinogenicity. To detect and analyze genetic events which contribute to nasal tumor development, we first defined the gene expressi...

Neoplastic and nonneoplastic liver lesions induced by dimethylinitrosamine in Japanese Medaka fish

EPA Science Inventory

Small fish models are becoming commonplace in the laboratory, and have been used for decades in chemical toxicity and carcinogenicity testing. However, extrapolation of findings from aquatic models to humans is still a concern in risk assessment. Demonstration of common morpholog...

Classification of corn kernels contaminated with aflatoxins using fluorescence and reflectance hyperspectral image analysis

USDA-ARS?s Scientific Manuscript database

Aflatoxins are secondary metabolites produced by certain fungal species of the Aspergillus genus. Aflatoxin contamination remains a problem in agricultural products due to its toxic and carcinogenic properties. Conventional chemical methods for aflatoxin detection are time-consuming and destructive....

URINARY BIOMARKERS OF DI-ISONONYL PHTHALATE IN RATS

EPA Science Inventory

Commercial di-isononyl phthalate (DiNP) is a mixture of various branched-chain dialkyl phthalates mainly containing ninecarbon alkyl isomers. At high doses in rodents, DiNP is a carcinogen, and a developmental toxicant. After exposure, the diester isomers are de-esterified to for...

Aspergillus flavus secondary metabolites: more than just aflatoxins

USDA-ARS?s Scientific Manuscript database

Aspergillus flavus is best known for producing the family of potent carcinogenic secondary metabolites known as aflatoxins. However, this opportunistic plant and animal pathogen also produces numerous other secondary metabolites, many of which have also been shown to be toxic. While about forty of t...

Occurrence and distribution of polycyclic aromatic hydrocarbons in surface sediments of San Diego Bay marinas.

PubMed

Neira, Carlos; Cossaboon, Jennifer; Mendoza, Guillermo; Hoh, Eunha; Levin, Lisa A

2017-01-15

Polycyclic aromatic hydrocarbons (PAHs) have garnered much attention due to their bioaccumulation, carcinogenic properties, and persistence in the environment. Investigation of the spatial distribution, composition, and sources of PAHs in sediments of three recreational marinas in San Diego Bay, California revealed significant differences among marinas, with concentrations in one site exceeding 16,000ngg -1 . 'Hotspots' of PAH concentration suggest an association with stormwater outfalls draining into the basins. High-molecular weight PAHs (4-6 rings) were dominant (>86%); the average percentage of potentially carcinogenic PAHs was high in all sites (61.4-70%) but ecotoxicological risks varied among marinas. Highly toxic benzo(a)pyrene (BaP) was the main contributor (>90%) to the total toxic equivalent quantity (TEQ) in marinas. PAHs in San Diego Bay marina sediments appear to be derived largely from pyrogenic sources, potentially from combustion products that reach the basins by aerial deposition and stormwater drainage from nearby streets and parking lots. Copyright © 2016 Elsevier Ltd. All rights reserved.

Biochemical and molecular aspects of mammalian susceptibility to aflatoxin B{sub 1} carcinogenicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Massey, T.E.; Stewart, R.K.; Daniels, J.M.

Aflatoxin B{sub 1} (AFB{sub 1}) is a fungal toxin that has been implicated as a causative agent in human hepatic and extrahepatic carcinogenesis. In this review, the mechanisms involved in AFB{sub 1} toxicity are delineated, in order to describe the features that make a specific cell, tissue, or species susceptible to the mycotoxin. Important considerations include: (i) different mechanisms for bioactivation of AFB{sub 1} to its ultimate carcinogenic epoxide metabolite; (ii) the balance between bioactivation to and detoxification of the epoxide; (iii) the interaction of AFB{sub 1} epoxide with DNA and the mutational events leading to neoplastic transformation; (iv) themore » role of cytotoxicity in AFB{sub 1} carcinogenesis; (v) the significance of nonepoxide metabolites in toxicity; and (vi) the contribution of mycotoxin-unrelated disease processes. Although considerable controversy remains about the importance of specific events, a great deal has been learned about biochemical and molecular actions of AFB{sub 1}. 157 refs., 4 figs., 1 tab.« less

An overview of the toxicology and toxicokinetics of fusarenon-X, a type B trichothecene mycotoxin.

PubMed

Aupanun, Sawinee; Poapolathep, Saranya; Giorgi, Mario; Imsilp, Kanjana; Poapolathep, Amnart

2017-01-20

Fusarenon-X (FX) is a type B trichothecene mycotoxin that is frequently observed along with deoxynivalenol (DON) and nivalenol (NIV) in agricultural commodities. This review aims to give an overview of the literature concerning the toxicology and toxicokinetics of FX. FX is primarily found in cereals grown in temperate regions, but it can also be found worldwide because of the global transport of products. The major toxicity of FX occurs through inhibition of protein synthesis, followed by the disruption of DNA synthesis. Moreover, FX has also been shown to induce apoptosis in in vitro and in vivo studies. The targets of FX are organs containing actively proliferating cells, such as the thymus, spleen, skin, small intestine, testes and bone marrow. FX causes immunosuppression, intestinal malabsorption, developmental toxicity and genotoxicity. In addition, sufficient evidence of carcinogenicity in experimental animals is currently lacking, and the International Agency for Research on Cancer (IARC) classifies it as a group 3 carcinogen.

Capturing Labile Sulfenamide and Sulfinamide Serum Albumin Adducts of Carcinogenic Arylamines by Chemical Oxidation

PubMed Central

Peng, Lijuan; Turesky, Robert J.

2013-01-01

Aromatic amines and heterocyclic aromatic amines (HAAs) are a class of structurally related carcinogens that are formed during the combustion of tobacco or during the high temperature cooking of meats. These procarcinogens undergo metabolic activation by N-oxidation of the exocyclic amine group to produce N-hydroxylated metabolites, which are critical intermediates implicated in toxicity and DNA damage. The arylhydroxylamines and their oxidized arylnitroso derivatives can also react with cysteine (Cys) residues of glutathione or proteins to form, respectively, sulfenamide and sulfinamide adducts. However, sulfur-nitrogen linked adducted proteins are often difficult to detect because they are unstable and undergo hydrolysis during proteolytic digestion. Synthetic N-oxidized intermediates of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a carcinogenic HAA produced in cooked meats, and 4-aminobiphenyl, a carcinogenic aromatic amine present in tobacco smoke were reacted with human serum albumin (SA) and formed labile sulfenamide or sulfinamide adducts at the Cys34 residue. Oxidation of the carcinogen-modified SA with m-chloroperoxybenzoic acid (m-CPBA) produced the arylsulfonamide adducts, which were stable to heat and the chemical reduction conditions employed to denature SA. The sulfonamide adducts of PhIP and 4-ABP were identified, by liquid chromatography/mass spectrometry, in proteolytic digests of denatured SA. Thus, selective oxidation of arylamine-modified SA produces stable arylsulfonamide-SA adducts, which may serve as biomarkers of these tobacco and dietary carcinogens. PMID:23240913

Context Matters: Contribution of Specific DNA Adducts to the Genotoxic Properties of the Tobacco-Specific Nitrosamine NNK.

PubMed

Peterson, Lisa A

2017-01-17

The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent pulmonary carcinogen in laboratory animals. It is classified as a Group 1 human carcinogen by the International Agency for Cancer Research. NNK is bioactivated upon cytochrome P450 catalyzed hydroxylation of the carbon atoms adjacent to the nitrosamino group to both methylating and pyridyloxobutylating agents. Both pathways generate a spectrum of DNA damage that contributes to the overall mutagenic and toxic properties of this compound. NNK is also reduced to form 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), which is also carcinogenic. Like NNK, NNAL requires metabolic activation to DNA alkylating agents. Methyl hydroxylation of NNAL generates pyridylhydroxybutyl DNA adducts, and methylene hydroxylation leads to DNA methyl adducts. The consequence of this complex metabolism is that NNK generates a vast spectrum of DNA damage, any form of which can contribute to the overall carcinogenic properties of this potent pulmonary carcinogen. This Perspective reviews the chemistry and genotoxic properties of the collection of DNA adducts formed from NNK. In addition, it provides evidence that multiple adducts contribute to the overall carcinogenic properties of this chemical. The adduct that contributes to the genotoxic effects of NNK depends on the context, such as the relative amounts of each DNA alkylating pathway occurring in the model system, the levels and genetic variants of key repair enzymes, and the gene targeted for mutation.

The need for independent research on the health effects of glyphosate-based herbicides.

PubMed

Landrigan, Philip J; Belpoggi, Fiorella

2018-05-29

Glyphosate, formulated as Roundup, is the world's most widely used herbicide. Glyphosate is used extensively on genetically modified (GM) food crops designed to tolerate the herbicide, and global use is increasing rapidly. Two recent reviews of glyphosate's health hazards report conflicting results. An independent review by the International Agency for Research on Cancer (IARC) found that glyphosate is a "probable human carcinogen". A review by the European Food Safety Agency (EFSA) found no evidence of carcinogenic hazard. These differing findings have produced regulatory uncertainty. Reflecting this regulatory uncertainty, the European Commission on November 27 2017, extended authorization for glyphosate for another 5 years, while the European Parliament opposed this decision and issued a call that pesticide approvals be based on peer-reviewed studies by independent scientists rather than on the current system that relies on proprietary industry studies. The Ramazzini Institute has initiated a pilot study of glyphosate's health hazards that will be followed by an integrated experimental research project. This evaluation will be independent of industry support and entirely sponsored by worldwide crowdfunding. The aim of the Ramazzini Institute project is to explore comprehensively the effects of exposures to glyphosate-based herbicides at current real-world levels on several toxicological endpoints, including carcinogenicity, long-term toxicity, neurotoxicity, endocrine disrupting effects, prenatal developmental toxicity, the microbiome and multi-generational effects.

Demonstration of carboxylesterase in cytology samples of human nasal respiratory epithelium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rodgers, D.A.; Nikula, K.J.; Avila, K.

1995-12-01

The epithelial lining of the nasal airways is a target for responses induced by a variety of toxicant exposures. The high metabolic capacity of this tissue has been suggested to play a role in both protection of the airways through detoxication of certain toxicants, as well as in activation of other compounds to more toxic metabolites. Specifically, nasal carboxylesterase (CE) has been shown to mediate the toxicity of inhaled esters and acrylates by converting them to more toxic acid and alcohol metabolites which can be cytotoxic and/or carcinogenic to the nasal mucosa. Due to difficulties in extrapolating rodent models tomore » human, new paradigms using human cells and tissues are essential to understanding and evaluating the metabolic processes in human nasal epithelium.« less

[Pathogenicity of artificial mineral fibers: are they as dangerous as asbestos?].

PubMed

Renzi, P M; Mantha, J; Matar, N; Renzi, G D

1990-01-01

Man-Made Mineral Fibres (MMMF) are starting to replace asbestos in the insulation industry. The popularity of these fibres has increased since the demonstration, in man, of the fibrogenicity and carcinogenicity of asbestos. A fear of human toxicity of MMMF has followed the demonstration of toxicity in animals after injection or instillation. This review of the litterature discusses the toxicity and side effects of MMMF. These fibres seem to have less toxicity than asbestos for the following reasons: 1. A lower concentration of fibres found in the air of the MMMF industry. 2. The cleavage of fibres in a perpendicular and non-parallel way. 3. The dissolution of fibres in the lung. Very fine fibreglass and mineral wool seem to be more toxic than continuous filaments and ordinary fibreglass.

A Literature Review - Problem Definition Studies on Selected Toxic Chemicals. Volume 2. Occupational Health and Safety Aspects of Phosphorus Smoke Compounds

DTIC Science & Technology

1978-04-01

1945. 24. Schautz, R.: [Occurrence of necrosis of both feet following local phosphorus burns.] Arztl Wchnschr 8:362-365, 1953 (German). 25...been found to be highly toxic to bcth experimental animals and humans. Occupational exposure to white phosphorus vapors has produced necrosis of the... necrosis of the jaw ("phossy jaw") among workers. There have been no reported cases of carcinogenicity in humans after white phos-. phorus intoxication

Using weeds to fight wastes

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1992-10-01

Researchers at Los Alamos National Laboratory and New Mexico State University have discovered that jimson weed and wild tomato plants can remove the toxic wastes in wastewater associated with the production of trinitrotoluene (TNT). According to Wolfgang F. Mueller of New Mexico State, tissue-cultured cells of jimson weed rapidly absorb and break down toxic and carcinogenic elements in {open_quotes}pink water,{close_quotes} a by-product of the manufacture of TNT. Mueller and his colleagues have found similar results with the wild tomato plant.

Chemically induced skin carcinogenesis: Updates in experimental models (Review)

PubMed Central

NEAGU, MONICA; CARUNTU, CONSTANTIN; CONSTANTIN, CAROLINA; BODA, DANIEL; ZURAC, SABINA; SPANDIDOS, DEMETRIOS A.; TSATSAKIS, ARISTIDIS M.

2016-01-01

Skin cancer is one of the most common malignancies affecting humans worldwide, and its incidence is rapidly increasing. The study of skin carcinogenesis is of major interest for both scientific research and clinical practice and the use of in vivo systems may facilitate the investigation of early alterations in the skin and of the mechanisms involved, and may also lead to the development of novel therapeutic strategies for skin cancer. This review outlines several aspects regarding the skin toxicity testing domain in mouse models of chemically induced skin carcinogenesis. There are important strain differences in view of the histological type, development and clinical evolution of the skin tumor, differences reported decades ago and confirmed by our hands-on experience. Using mouse models in preclinical testing is important due to the fact that, at the molecular level, common mechanisms with human cutaneous tumorigenesis are depicted. These animal models resemble human skin cancer development, in that genetic changes caused by carcinogens and pro-inflammatory cytokines, and simultaneous inflammation sustained by pro-inflammatory cytokines and chemokines favor tumor progression. Drugs and environmental conditions can be tested using these animal models. keeping in mind the differences between human and rodent skin physiology. PMID:26986013

Acute, subchronic, and developmental toxicological properties of lubricating oil base stocks.

PubMed

Dalbey, Walden E; McKee, Richard H; Goyak, Katy Olsavsky; Biles, Robert W; Murray, Jay; White, Russell

2014-01-01

Lubricating oil base stocks (LOBs) are substances used in the manufacture of finished lubricants and greases. They are produced from residue remaining after atmospheric distillation of crude oil that is subsequently fractionated by vacuum distillation and additional refining steps. Initial LOB streams that have been produced by vacuum distillation but not further refined may contain polycyclic aromatic compounds (PACs) and may present carcinogenic hazards. In modern refineries, LOBs are further refined by multistep processes including solvent extraction and/or hydrogen treatment to reduce the levels of PACs and other undesirable constituents. Thus, mildly (insufficiently) refined LOBs are potentially more hazardous than more severely (sufficiently) refined LOBs. This article discusses the evaluation of LOBs using statistical models based on content of PACs; these models indicate that insufficiently refined LOBs (potentially carcinogenic LOBs) can also produce systemic and developmental effects with repeated dermal exposure. Experimental data were also obtained in ten 13-week dermal studies in rats, eight 4-week dermal studies in rabbits, and seven dermal developmental toxicity studies with sufficiently refined LOBs (noncarcinogenic and commonly marketed) in which no observed adverse effect levels for systemic toxicity and developmental toxicity were 1000 to 2000 mg/kg/d with dermal exposures, typically the highest dose tested. Results in both oral and inhalation developmental toxicity studies were similar. This absence of toxicologically relevant findings was consistent with lower PAC content of sufficiently refined LOBs. Based on data on reproductive organs with repeated dosing and parameters in developmental toxicity studies, sufficiently refined LOBs are likely to have little, if any, effect on reproductive parameters.

A CONCISE REVIEW OF THE TOXICITY AND CARCINOGENICITY OF DIMETHYLARSINIC ACID

EPA Science Inventory

Dimethylarsinic acid (DMA) has been used as an herbicide (cacodylic acid) and is the major metabolite formed after exposure to tri- (arsenite) or pentavalent (arsenate) inorganic arsenic (iAs) via ingestion or inhalation in both humans and rodents. Once viewed simply as a detoxi...

Atypical Aspergillus parasiticus isolates from pistachio with aflR gene nucleotide insertion identical to Aspergillus sojae

USDA-ARS?s Scientific Manuscript database

Aflatoxins are the most toxic and carcinogenic secondary metabolites produced primarily by the filamentous fungi Aspergillus flavus and Aspergillus parasiticus. The toxins cause devastating economic losses because of strict regulations on distribution of contaminated products. Aspergillus sojae are...

Development of a Multiroute Human PBPK Model for Bromodichloromethane (BDCM)

EPA Science Inventory

BDCM is an animal carcinogen and developmental toxicant. Due to its presence as a disinfection byproduct in finished drinking water, BDCM may pose a risk for exposure via ingestion, inhalation or dermal exposure. Utilizing a unique data set in which human subjects were exposed ...

DEVELOPMENT OF AN IN SITU TOXICITY ASSAY SYSTEM USING RECOMBINANT BACULOVIRUSES. (R825433)

EPA Science Inventory

A new method for experimentally analyzing the role of enzymes involved in metabolizing mutagenic, carcinogenic, or cytotoxic chemicals is described. Spodoptera fugiperda (SF-21) cells infected with recombinant baculoviruses are used for high level expression of one or m...

Identification and functional analysis of the aspergillic acid gene cluster in Aspergillus flavus

USDA-ARS?s Scientific Manuscript database

Aspergillus flavus can colonize important food staples and produces aflatoxins, toxic and carcinogenic secondary metabolites. In silico analysis of the A. flavus genome revealed 56 gene clusters encoding for secondary metabolites. How these many of these metabolites affect fungal development, surviv...

The importance of being thiomethylated: formation, fate, and effects of methylated thioarsenicals

EPA Science Inventory

AbstractAlthough inorganic arsenic has long been recognized as a potent toxicant and carcinogen in humans, recent evidence shows that at least some of its effects are mediated by methylated metabolites. Elucidating the conversion of inorganic arsenic to mono-, di-, and tri-methyl...

OVERVIEW OF THE MUTAGENICITY OF URBAN AIR

EPA Science Inventory

For the past 25 years, there has been great interest in the mutagenicity and carcinogenicity of ambient air and in the sources of those genotoxicants. Prior to the 1980's, the evaluation of airborne toxicants was done on a pollutant-by-pollutant basis. However, the assessment of ...

Genomic effects of androstenedione and sex-specific liver cancer susceptibility in mice

EPA Science Inventory

Current strategies for predicting carcinogenic mode of action for nongenotoxic chemicals are based on identification of early key events in toxicity pathways. The goal of this study was to evaluate short-term key event indicators resulting from exposure to androstenedione (A4), a...

Detection of contaminated hazelnuts and ground red chili pepper flakes by multispectral imaging

USDA-ARS?s Scientific Manuscript database

Mycotoxins are the toxic metabolites of certain filamentous fungi and have been demonstrated to cause various health problems in humans, including immunosuppression and cancer. Among them, the aflatoxins have received greater attention because they are potent carcinogens and are responsible for many...

Detecting peanuts inoculated with toxigenic and atoxienic Aspergillus flavus strains with fluorescence hyperspectral imagery

USDA-ARS?s Scientific Manuscript database

Aflatoxin contamination in peanut products has been an important and long-standing problem around the world. Produced mainly by Aspergillus flavus and Aspergillus parasiticus, aflatoxins are the most toxic and carcinogenic compounds among toxins. This study investigated the application of fluorescen...

PEPTIDE BINDING AS A MODE OF ACTION FOR THE CARCINOGENICITY AND TOXICITY OF ARSENIC

EPA Science Inventory

Arsenic exposure leads to tumors in human skin, lung, urinary bladder, kidney and liver. Three likely initial stages of arsenical-macromolecular interaction are (1) binding of trivalent arsenicals to the sulfhydryl groups of peptides and proteins, (2) arsenical-induced generation...

Molecular Characterization of Atoxigenic Strains for Biological Control of Aflatoxins in Nigeria

USDA-ARS?s Scientific Manuscript database

Aflatoxins are highly toxic, carcinogens produced by several species in Aspergillus section Flavi. Strains of A. flavus that do not produce aflatoxins, called atoxigenic strains, have been used commercially in North America as tools for limiting aflatoxin contamination. A similar aflatoxin manage...

Detection of genotoxic and non-genotoxic carcinogens in Xpc{sup −/−}p53{sup +/−} mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Melis, Joost P.M.; Leiden University Medical Center, Department of Toxicogenetics, Leiden; Speksnijder, Ewoud N.

2013-01-15

An accurate assessment of the carcinogenic potential of chemicals and pharmaceutical drugs is essential to protect humans and the environment. Therefore, substances are extensively tested before they are marketed to the public. Currently, the rodent two-year bioassay is still routinely used to assess the carcinogenic potential of substances. However, over time it has become clear that this assay yields false positive results and also has several economic and ethical drawbacks including the use of large numbers of animals, the long duration, and the high cost. The need for a suitable alternative assay is therefore high. Previously, we have proposed themore » Xpa*p53 mouse model as a very suitable alternative to the two-year bioassay. We now show that the Xpc*p53 mouse model preserves all the beneficial traits of the Xpa*p53 model for sub-chronic carcinogen identification and can identify both genotoxic and non-genotoxic carcinogens. Moreover, Xpc*p53 mice appear to be more responsive than Xpa*p53 mice towards several genotoxic and non-genotoxic carcinogens. Furthermore, Xpc*p53 mice are far less sensitive than Xpa*p53 mice for the toxic activity of DNA damaging agents and as such clearly respond in a similar way as wild type mice do. These advantageous traits of the Xpc*p53 model make it a better alternative for in vivo carcinogen testing than Xpa*p53. This pilot study suggests that Xpc*p53 mice are suited for routine sub-chronic testing of both genotoxic and non-genotoxic carcinogens and as such represent a suitable alternative to possibly replace the murine life time cancer bioassay. Highlights: ► The Xpc*p53 mouse model is able to identify genotoxic and non-genotoxic carcinogens. ► Time, animals and cost can be significantly reduced compared to the 2-year bioassay. ► Xpc*p53 mice are more advantageous for carcinogen identification than Xpa*p53 mice. ► Xpc*p53 mice exhibit a wild type response upon exposure to genotoxicants.« less

Toxic effects of brominated flame retardants in man and in wildlife.

PubMed

Darnerud, Per Ola

2003-09-01

Brominated flame retardants (BFRs) are ubiquitous industrial chemicals, and many of them are produced in large volumes. Due to this fact, several BFRs are found in quantifiable levels in wildlife, as well as in humans. However, we are still lacking information on the effects of BFR in wildlife and, especially, in man. This review summarises the biological effects of polybrominated diphenyl ethers (PBDEs), tetrabromobisphenol A (TBBPA) and derivates, hexabromocyclododecane (HBCD) and polybrominated biphenyls (PBBs), however excluding other aspects such as environmental levels. These BFR groups were selected because of a large volume production (PBDEs, TBBPA and derivates), and availability of some toxicity data in spite of much lower production volumes (HBCD and PBBs). In addition, the increase in levels of PBDEs in human (breast milk) and wildlife samples during later time made it especially interesting to include this BFR group. PBDES: The commercial PBDE products predominantly consist of so-called penta-, octa- and decabromodiphenyl ether products. Each product consists of a rather narrow range of congeners and is named after the dominating congener as regards the bromination pattern. Generally, the PentaBDEs seem to cause adverse effects at the comparably lowest dose, whereas much higher doses were needed for effects of the DecaBDEs. The critical effects of PentaBDEs are those on neurobehavioural development (from 0.6 mg/kg body weight) and, at somewhat higher dose, thyroid hormone levels in rats and mice, of OctaBDEs on fetal toxicity/teratogenicity in rats and rabbits (from 2 mg/kg body weight), and of DecaBDEs on thyroid, liver and kidney morphology in adult animals (from 80 mg/kg body weight). Carcinogenicity studies, only performed for DecaBDEs, show some effects at very high levels, and IARC (1990) evaluates DecaBDEs not classifiable as to its carcinogenicity to humans. TBBPA: The toxicity of TBBPA in the experimental in vivo studies is suggested to be low. In most reported studies, only doses in g/kg body weight were effective, but at least one study suggested renal effects at around 250 mg/kg body weight. Although difficult to include and interpret in a quantitative risk assessment, the in vitro effects on immunological and thyroid hormones, as well as binding to erythrocytes should be noted. Before a solid standpoint could be reached on TBBPA toxicity additional studies must be performed. This statement is even more valid regarding the TBBPA derivates, where there is an almost complete lack of toxicity data. HBCD: Also in the case of HBCD, relevant toxicity studies are lacking. Based on the present animal studies, a critical effect is seen in the liver and on thyroid hormones (LOAEL 100 mg/kg body weight/day). However, in a recent short paper behavioural effects in mice pups were observed already at 0.9 mg/kg body weight, and behavioural effects may be a sensitive endpoint for HBCD, as well as for other BFRs. PBBS: Due to the Michigan accident in 1973-1974, many toxicity studies on PBBs are available. The critical experimental effects are those on reproduction and carcinogenicity, and a NOAEL of 0.15 mg/kg body weight/day could be suggested based on the cancer effects. In man no unequivocal effects have been observed, although in some studies neurological and musculoskeletal symptoms were suggested. Based on the carcinogenic effects in animals, a human TDI of 0.15 microg/kg body weight has been presented. To conclude, the toxicity data are almost entirely based on experimental models. There are differences among the BFR groups, as well as within these groups, both regarding type of toxic effect and at what dose it appears. As BFRs will continue to appear both in industrial applications and, even if the production has ceased, in our environment, there is a continued need for effects studies on BFRs.

Toxic and genotoxic effects of hexavalent chromium in environment and its bioremediation strategies.

PubMed

Mishra, Sandhya; Bharagava, Ram Naresh

2016-01-01

Chromium is one of the major inorganic environmental pollutants, which is added in the environment through various natural and anthropogenic activities and exists mainly in two forms: Cr(III) and Cr(VI). Cr(VI) is considered to be more toxic than Cr(III) due to its high solubility and mobility. It is a well-reported occupational carcinogen associated with lung, nasal, and sinus cancers. Thus, this review article provides the detailed information on the occurrence, sources of chromium contamination in the environment and their toxicological effects in human, animal, plants as well as in microorganisms, and bioremediation strategies to minimize the toxic effects.

Conference summary & recent advances: The 8th Conference on Metal Toxicity and Carcinogenesis

PubMed Central

Zhou, Xixi; Burchiel, Scott W.; Hudson, Laurie G.; Liu, Ke Jian

2015-01-01

Diseases caused by occupational and environmental exposure to metals are a public health concern. The underlying molecular mechanisms of metal toxicity and carcinogenicity remain largely unknown. Over 130 scientists attended the 8th Conference on Metal Toxicity and Carcinogenesis, presenting their various research concerns and recent findings to stimulate interactions and collaborations among scientists in the field. Several major areas were emphasized, including human & population studies, molecular & cellular mechanisms, biological targets, epigenetic effects, metabolism, and metal mixtures. Here we summarize presentations at the conference sessions and highlight the attendees’ latest work published in this special issue of Biological Trace Element Research. PMID:25975949

Risk-based indicators of Canadians' exposures to environmental carcinogens.

PubMed

Setton, Eleanor; Hystad, Perry; Poplawski, Karla; Cheasley, Roslyn; Cervantes-Larios, Alejandro; Keller, C Peter; Demers, Paul A

2013-02-12

Tools for estimating population exposures to environmental carcinogens are required to support evidence-based policies to reduce chronic exposures and associated cancers. Our objective was to develop indicators of population exposure to selected environmental carcinogens that can be easily updated over time, and allow comparisons and prioritization between different carcinogens and exposure pathways. We employed a risk assessment-based approach to produce screening-level estimates of lifetime excess cancer risk for selected substances listed as known carcinogens by the International Agency for Research on Cancer. Estimates of lifetime average daily intake were calculated using population characteristics combined with concentrations (circa 2006) in outdoor air, indoor air, dust, drinking water, and food and beverages from existing monitoring databases or comprehensive literature reviews. Intake estimates were then multiplied by cancer potency factors from Health Canada, the United States Environmental Protection Agency, and the California Office of Environmental Health Hazard Assessment to estimate lifetime excess cancer risks associated with each substance and exposure pathway. Lifetime excess cancer risks in excess of 1 per million people are identified as potential priorities for further attention. Based on data representing average conditions circa 2006, a total of 18 carcinogen-exposure pathways had potential lifetime excess cancer risks greater than 1 per million, based on varying data quality. Carcinogens with moderate to high data quality and lifetime excess cancer risk greater than 1 per million included benzene, 1,3-butadiene and radon in outdoor air; benzene and radon in indoor air; and arsenic and hexavalent chromium in drinking water. Important data gaps were identified for asbestos, hexavalent chromium and diesel exhaust in outdoor and indoor air, while little data were available to assess risk for substances in dust, food and beverages. The ability to track changes in potential population exposures to environmental carcinogens over time, as well as to compare between different substances and exposure pathways, is necessary to support comprehensive, evidence-based prevention policy. We used estimates of lifetime excess cancer risk as indicators that, although based on a number of simplifying assumptions, help to identify important data gaps and prioritize more detailed data collection and exposure assessment needs.

Livestock Poisoning with Pyrrolizidine Alkaloid Containing Plants (Senecio, Crotalaria, Cynoglossum, Amsinckia, Heliotropium and Echium spp.)

USDA-ARS?s Scientific Manuscript database

Pyrrolizidine alkaloids (PAs) are potent liver toxins that have been identified in over 6,000 plants throughout the world. Alkaloids are nitrogen-based compounds with potent biological activity. About half of the identified PAs are toxic and several cause cancer (carcinogenic). PA-containing plants...

EFFECTS OF HEAT SHOCK PROTEIN 70 (HSP70) ON ARSENITE INDUCED GENOTOXICITY

EPA Science Inventory

Arsenic (As), a human carcinogen, is known to be genotoxic although its mechanism(s) of action for tumorigenesis is not well understood. Among the toxicity-related properties of this chemical are its clastogenic and aneugenic activities, as well as its capacity for inducing stres...

BIOCATALYTIC POLYMERIZATION OF NATURALLY OCCURRING GREEN TEA FLAVONOIDS FOR CANCER THERAPY

EPA Science Inventory

The upsurge in the discovery, development and use of new materials and drugs has resulted in large-scale production of potentially toxic, carcinogenic intermediates and by-products leading to an outburst in the number of cancer cases. In the U.S. alone one in four dea...

ASSESSING ARSENIC EXPOSURE AND SKIN HYPERKERATOSIS IN INNER MONGOLIA, CHINA

EPA Science Inventory

Arsenic is a known human carcinogen. The inorganic forms, especially arsenite (As+3), are believed to be the most toxic species. Methylation is often considered to be the
detoxification pathway for the metabolism of inorganic arsenic. The ground water in Ba
Men, Inner Mo...

GENE PROFILING IN WILD TYPE AND PPARÁ NULL MICE EXPOSED TO PFOA

EPA Science Inventory

Perflurooctanoic acid (PFOA) is a perfluoroalkyl acid used in a variety of commercial applications. Concerns have been raised because PFOA is ubiquitous in the environment and can be detected in human tissues. PFOA is a rodent carcinogen and a developmental toxicant in mice. W...

CHROMATOGRAPHIC SEPARATION AND IDENTIFICATION OF PRODUCTS FROM THE REACTION OF DIMETHYLARSINIC ACID WITH HYDROGEN SULFIDE

EPA Science Inventory

The reaction of dimethylarsinic acid (DMAV) with hydrogen sulfide (H2S) is of biological significance and may be implicated in the overall toxicity and carcinogenicity of arsenic. The course of the reaction in aqueous phase was monitored and an initial product, dimethylthioarsin...

STUDIES OF NORMAL GENE EXPRESSION IN THE RAT NASAL EPITHELIUM USNG CDNA ARRAY TECHNOLOGY

EPA Science Inventory

Studies of Normal Gene Expression in the Rat Nasal Epithelium Using cDNA Array

The nasal epithelium is an important target site for chemically-induced toxicity and carcinogenicity .Gene expression data are being used increasingly for studies of such conditions. In or...

Introduction of Atrazine-Degrading Pseudomonas SP. Strain ADP to Enhance Phytoremediation of Atrazine

USDA-ARS?s Scientific Manuscript database

Atrazine (ATR) has been widely applied in the US Midwestern states. Public health and ecological concerns have been raised about contamination of surface and ground water by ATR and its chlorinated metabolites, due to their toxicity and potential carcinogenic or endocrinology effects. Phytoremediati...

Development of Carcinogenesis Bioassay Models: Response of Small Fish Species to Various Classes of Carcinogens

DTIC Science & Technology

1989-12-14

induces injection-site sarcomas (mainly fibrosarcomas and rhabdomyosarcomas) as well as reproductive toxicity and neoplasms in males (Haddow et al...G., and Ward, J.M., 1981. Characteristics of proliferative lesions in the nasal cavities of mice following chronic inhalation of EDB. Cancer Lett., 12

40 CFR 799.9430 - TSCA combined chronic toxicity/carcinogenicity.

Code of Federal Regulations, 2010 CFR

2010-07-01

... effects and determine dose-response relationships. The design and conduct should allow for the detection... dynamic inhalation equipment designed to sustain a minimum air flow of 10 air changes per hour, an... measurements during the exposures should be sufficient. If pretest measurements are not within 10% of each...

40 CFR 799.9430 - TSCA combined chronic toxicity/carcinogenicity.

Code of Federal Regulations, 2011 CFR

2011-07-01

... effects and determine dose-response relationships. The design and conduct should allow for the detection... dynamic inhalation equipment designed to sustain a minimum air flow of 10 air changes per hour, an... measurements during the exposures should be sufficient. If pretest measurements are not within 10% of each...

40 CFR 799.9430 - TSCA combined chronic toxicity/carcinogenicity.

Code of Federal Regulations, 2013 CFR

2013-07-01

... effects and determine dose-response relationships. The design and conduct should allow for the detection... dynamic inhalation equipment designed to sustain a minimum air flow of 10 air changes per hour, an... measurements during the exposures should be sufficient. If pretest measurements are not within 10% of each...

40 CFR 799.9430 - TSCA combined chronic toxicity/carcinogenicity.

Code of Federal Regulations, 2012 CFR

2012-07-01

... effects and determine dose-response relationships. The design and conduct should allow for the detection... dynamic inhalation equipment designed to sustain a minimum air flow of 10 air changes per hour, an... measurements during the exposures should be sufficient. If pretest measurements are not within 10% of each...

40 CFR 799.9430 - TSCA combined chronic toxicity/carcinogenicity.

Code of Federal Regulations, 2014 CFR

2014-07-01

... effects and determine dose-response relationships. The design and conduct should allow for the detection... dynamic inhalation equipment designed to sustain a minimum air flow of 10 air changes per hour, an... measurements during the exposures should be sufficient. If pretest measurements are not within 10% of each...

AN ENZYME-LINKED IMMUNOSORBENT ASSAY (ELISA) FOR DETERMINING DIOXINS IN SEDIMENT AND SOIL SAMPLES

EPA Science Inventory

The dioxins comprise a family of compounds chemically referred to as polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). The most toxic of these compounds is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a known human carcinogen. Dioxins are formed ...

MULTIMEDIA CHEMICAL ANALYSIS PLAN FOR CHILDREN'S AGGREGATE EXPOSURE FIELD STUDIES IN NORTH CAROLINA AND OHIO

EPA Science Inventory

The samples collected in the CTEPP North Carolina and Ohio field campaigns were analyzed for a suite of organic chemicals in various compound classes, chosen because of their possible carcinogenicity, acute or chronic toxicity, or potential for endocrine system disruption. The...

Characterization of stuA mutants in the mycotoxigenic maize pathogen Fusarium verticillioides

USDA-ARS?s Scientific Manuscript database

Fusarium verticillioides is a major pathogen of maize, causing root, stalk and ear rots and seedling blight. It also produces fumonisin mycotoxins. Ingestion of fumonisin-contaminated corn causes acute toxicity in livestock and is a potential carcinogen to humans. StuA, an APSES protein class transc...

MODES OF ACTION FOR THE CARCINOGENICITY AND TOXICITY OF ARSENIC - MOVING TOWARDS A MORE QUANTITATIVE RISK ASSESSMENT

EPA Science Inventory

Arsenic exposures can lead to human tumors in skin, lung, urinary bladder, kidney and liver. Three likely initial stages of arsenical¬macromolecular interaction are (1) binding of trivalent arsenicals to sulfhydryl groups of peptides and proteins, (2) arsenical-induced generation...

USE OF THE JAPANESE MEDAKA (ORYZIAS LATIPES) AND GUPPY (POECILIA RETICULATA) IN CARCINOGENESIS TESTING UNDER NATIONAL TOXICOLOGY PROGRAM PROTOCOLS

EPA Science Inventory

that are economical, sensitive, and scientifically acceptable. Among small fish models, the Japanese medaka (Oryzias latipes) is preeminent for investigating effects of carcinogenic and/or toxic waterborne hazards to humans. The guppy (Poecilia reticulata), although less widely u...

Evaluation of the expression genes associated with resistance to Aspergillus flavus colonization and aflatoxin production in different maize lines.

USDA-ARS?s Scientific Manuscript database

Aflatoxins are carcinogenic toxic compounds produced by Aspergillus flavus during infection of crops including maize (Zea mays L.). Contamination of maize with aflatoxin is exacerbated by late season drought stress. Previous studies have implicated numerous resistance-associated proteins (RAPs) that...

75 FR 72727 - Addition of National Toxicology Program Carcinogens; Community Right-to-Know Toxic Chemical...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-26

... is (202) 566-1752. FOR FURTHER INFORMATION CONTACT: Daniel R. Bushman, Environmental Analysis Division, Office of Information Analysis and Access (2842T), Environmental Protection Agency, 1200... Environmental Information, Office of Information Analysis and Access. August 12, 2010. 4. NTP, 2005. National...

EPA STUDIES OF ARSENIC SPECIATION IN SEAFOOD MATRICES WITH AN EMPHASIS ON EXTRACTABILITY AND ARSENOSUGAR INTEGRITY

EPA Science Inventory

The anthropogenic and geological occurrence of arsenic (As) results in human exposure to a potentially carcinogenic element. The two predominant pathways to As exposure are drinking water (DW) and dietary ingestion (DI). DW exposures are almost exclusively toxic inorganic As. ...

29 CFR 1926.1103 - 13 carcinogens (4-Nitrobiphenyl, etc.).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 1926.1103 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR CONSTRUCTION Toxic and Hazardous Substances... work under this section are identical to those set forth at § 1910.1003 of this chapter. [61 FR 31433...

Hydroxylic solvent-induced ring opening of the dehydropyrrolizidine alkaloids riddelliine and seneciphylline: implications for toxicity and analytical studies

USDA-ARS?s Scientific Manuscript database

etabolites that can also cause various cancers in animal models. Riddelliine and seneciphylline are closely-related, macrocyclic diester dehydropyrrolizidine alkaloids produced by various species in the Asteraceae. Despite the evidence of carcinogenicity in animal models, and the increasing concerns...

Minireview on the toxicity of dietary acrylamide.

PubMed

Parzefall, Wolfram

2008-04-01

Acrylamide is a commodity chemical with many industrial and laboratory uses. It is also formed from carbohydrate and amino acid containing food by heating (primarily in fried potato products, bread, coffee). Neurotoxicity was detected as the primary toxic effect after occupational exposure. In rats and mice AA is toxic for reproduction and development and to male germ cells, is genotoxic through a reactive metabolite, glycidamide, and carcinogenic to several organs. Epidemiological studies did not point to an association between either occupational or dietary exposure and an excess of cancer incidence. Health risks of the general population are based on an average exposure to 1 microg/kg bw/day increasing for high consumers to 4 microg/kg bw/day. For average consumers a margin of exposure of 200 for neurotoxicity can be regarded as sufficiently protective. However, a margin of 300 for carcinogenic risks appears not sufficient when applying a precautionary principle. This is also illustrated when the benchmark dose lower confidence limit for cancer is divided by an uncertainty factor of 300, which arrives at a tolerable daily intake of 1 microg/kg bw/day, and thus is in the range of average consumption. Further measures to minimize acrylamide formation in food should therefore be explored to reduce human exposure.

Enzymes oxidizing the azo dye 1-phenylazo-2-naphthol (Sudan I) and their contribution to its genotoxicity and carcinogenicity.

PubMed

Stiborova, Marie; Schmeiser, Heinz H; Frei, Eva; Hodek, Petr; Martinek, Vaclav

2014-01-01

Sudan I [1-(phenylazo)-2-naphthol, C.I. Solvent Yellow 14] is an industrial dye, which was found as a contaminant in numerous foods in several European countries. Because Sudan I has been assigned by the IARC as a Category 3 carcinogen, the European Union decreed that it cannot be utilized as food colorant in any European country. Sudan I induces the malignancies in liver and urinary bladder of rats and mice. This carcinogen has also been found to be a potent mutagen, contact allergen and sensitizer, and exhibits clastogenic properties. The oxidation of Sudan I increases its toxic effects and leads to covalent adducts in DNA. Identification of enzymatic systems that contribute to Sudan I oxidative metabolism to reactive intermediates generating such covalent DNA adducts on the one hand, and to the detoxification of this carcinogen on the other, is necessary to evaluate susceptibility to this toxicant. This review summarizes the identification of such enzymes and the molecular mechanisms of oxidation reactions elucidated to date. Human and animal cytochrome P450 (CYP) and peroxidases are capable of oxidizing Sudan I. Of the CYP enzymes, CYP1A1 is most important both in Sudan I detoxification and its bio-activation. Ring-hydroxylated metabolites and a dimer of this carcinogen were found as detoxification products of Sudan I generated with CYPs and peroxidases, respectively. Oxidative bio-activation of this azo dye catalyzed by CYPs and peroxidases leads to generation of proximate genotoxic metabolites (the CYP-catalyzed formation of the benzenediazonium cation and the peroxidase-mediated generation of one-electron oxidation products), which covalently modify DNA both in vitro and in vivo. The predominant DNA adduct generated with the benzenediazonium cation was characterized to be 8-(phenylazo)guanine. The Sudan I radical species mediated by peroxidases reacts with the -NH2 group in (deoxy)guanosine, generating the 4-[(deoxy)guanosin-N(2)-yl]Sudan I product. Sudan I was also found to be a strong inducer of CYP1A1 and its enzyme activity mediated by the aryl hydrocarbon receptor, thereby increasing its own genotoxic potential and the cancer risk for humans.

Carcinogenicity of methyl-tertiary butyl ether in gasoline.

PubMed

Mehlman, Myron A

2002-12-01

Methyl tertiary butyl ether (MTBE) was added to gasoline on a nationwide scale in 1992 without prior testing of adverse, toxic, or carcinogenic effects. Since that time, numerous reports have appeared describing adverse health effects of individuals exposed to MTBE, both from inhalation of fumes in the workplace and while pumping gasoline. Leakage of MTBE, a highly water-soluble compound, from underground storage tanks has led to contamination of the water supply in many areas of the United States. Legislation has been passed by many states to prohibit the addition of MTBE to gasoline. The addition of MTBE to gasoline has not accomplished its stated goal of decreasing air pollution, and it has posed serious health risks to a large portion of the population, particularly the elderly and those with respiratory problems, asthma, and skin sensitivity. Reports of animal studies of carcinogenicity of MTBE began to appear in the 1990s, prior to the widespread introduction of MTBE into gasoline. These reports were largely ignored. In ensuing years, further studies have shown that MTBE causes various types of malignant tumors in mice and rats. The National Toxicology Program (NTP) Board of Scientific Counselors' Report on Carcinogens Subcommittee met in December 1998 to consider listing MTBE as "reasonably anticipated to be a human carcinogen." In spite of recommendations from Dr. Bailer, the primary reviewer, and other scientists on the committee, the motion to list MTBE in the report was defeated by a six to five vote, with one abstention. On the basis of animal studies, it is widely accepted that if a chemical is carcinogenic in appropriate laboratory animal test systems, it must be treated as though it were carcinogenic in humans. In the face of compelling evidence, NTP Committee members who voted not to list MTBE as "reasonably anticipated to be a human carcinogen" did a disservice to the general public; this action may cause needless exposure of many to health risks and possibly cancers.

Hazardous Compounds in Tobacco Smoke

PubMed Central

Talhout, Reinskje; Schulz, Thomas; Florek, Ewa; van Benthem, Jan; Wester, Piet; Opperhuizen, Antoon

2011-01-01

Tobacco smoke is a toxic and carcinogenic mixture of more than 5,000 chemicals. The present article provides a list of 98 hazardous smoke components, based on an extensive literature search for known smoke components and their human health inhalation risks. An electronic database of smoke components containing more than 2,200 entries was generated. Emission levels in mainstream smoke have been found for 542 of the components and a human inhalation risk value for 98 components. As components with potential carcinogenic, cardiovascular and respiratory effects have been included, the three major smoke-related causes of death are all covered by the list. Given that the currently used Hoffmann list of hazardous smoke components is based on data from the 1990s and only includes carcinogens, it is recommended that the current list of 98 hazardous components is used for regulatory purposes instead. To enable risk assessment of components not covered by this list, thresholds of toxicological concern (TTC) have been established from the inhalation risk values found: 0.0018 μg day−1 for all risks, and 1.2 μg day−1 for all risks excluding carcinogenicity, the latter being similar to previously reported inhalation TTCs. PMID:21556207

Elucidating the mechanisms of nickel compound uptake: A review of particulate and nano-nickel endocytosis and toxicity

PubMed Central

Muñoz, Alexandra; Costa, Max

2012-01-01

Nickel (Ni) is a worldwide pollutant and contaminant that humans are exposed to through various avenues resulting in multiple toxic responses - most alarming is its clear carcinogenic nature. A variety of particulate Ni compounds persist in the environment and can be distinguished by characteristics such as solubility, structure, and surface charge. These characteristics influence cellular uptake and toxicity. Some particulate forms of Ni are carcinogenic and are directly and rapidly endocytized by cells. A series of studies conducted in the 1980’s observed this process, and we have reanalyzed the results of these studies to help elucidate the molecular mechanism of particulate Ni uptake. Originally the process of uptake observed was described as phagocytosis, however in the context of recent research we hypothesize that the process is macropinocytosis and/or clathrin mediated endocytosis. Primary considerations in determining the route of uptake here include calcium dependence, particle size, and inhibition through temperature and pharmacological approaches. Particle characteristics that influenced uptake include size, charge, surface characteristics, and structure. This discussion is relevant in the context of nanoparticle studies and the emerging interest in nano-nickel (nano-Ni), where toxicity assessments require a clear understanding of the parameters of particulate uptake and where establishment of such parameters is often obscured through inconsistencies across experimental systems. In this regard, this review aims to carefully document one system (particulate nickel compound uptake) and characterize its properties. PMID:22206756

Toxicity of the Organophosphate Chemical Warfare Agents GA, GB, and VX: Implications for Public Protection.

PubMed Central

Munro, N

1994-01-01

The nerve agents, GA, GB, and VX are organophosphorus esters that form a major portion of the total agent volume contained in the U.S. stockpile of unitary chemical munitions. Congress has mandated the destruction of these agents, which is currently slated for completion in 2004. The acute, chronic, and delayed toxicity of these agents is reviewed in this analysis. The largely negative results from studies of genotoxicity, carcinogenicity, developmental, and reproductive toxicity are also presented. Nerve agents show few or delayed effects. At supralethal doses, GB can cause delayed neuropathy in antidote-protected chickens, but there is no evidence that it causes this syndrome in humans at any dose. Agent VX shows no potential for inducing delayed neuropathy in any species. In view of their lack of genotoxcity, the nerve agents are not likely to be carcinogens. The overreaching concern with regard to nerve agent exposure is the extraordinarily high acute toxicity of these substances. Furthermore, acute effects of moderate exposure such as nausea, diarrhea, inability to perform simple mental tasks, and respiratory effects may render the public unable to respond adequately to emergency instructions in the unlikely event of agent releaase, making early warning and exposure avoidance important. Likewise, exposure or self-contamination of first responders and medical personnel must be avoided. Control limits for exposure via surface contact of drinking water are needed, as are detection methods for low levels in water or foodstuffs. Images Figure 2. PMID:9719666

Elucidating the mechanisms of nickel compound uptake: A review of particulate and nano-nickel endocytosis and toxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muñoz, Alexandra; Costa, Max, E-mail: Max.Costa@nyumc.org

Nickel (Ni) is a worldwide pollutant and contaminant that humans are exposed to through various avenues resulting in multiple toxic responses — most alarming is its clear carcinogenic nature. A variety of particulate Ni compounds persist in the environment and can be distinguished by characteristics such as solubility, structure, and surface charge. These characteristics influence cellular uptake and toxicity. Some particulate forms of Ni are carcinogenic and are directly and rapidly endocytized by cells. A series of studies conducted in the 1980s observed this process, and we have reanalyzed the results of these studies to help elucidate the molecular mechanismmore » of particulate Ni uptake. Originally the process of uptake observed was described as phagocytosis, however in the context of recent research we hypothesize that the process is macropinocytosis and/or clathrin mediated endocytosis. Primary considerations in determining the route of uptake here include calcium dependence, particle size, and inhibition through temperature and pharmacological approaches. Particle characteristics that influenced uptake include size, charge, surface characteristics, and structure. This discussion is relevant in the context of nanoparticle studies and the emerging interest in nano-nickel (nano-Ni), where toxicity assessments require a clear understanding of the parameters of particulate uptake and where establishment of such parameters is often obscured through inconsistencies across experimental systems. In this regard, this review aims to carefully document one system (particulate nickel compound uptake) and characterize its properties.« less

A review of the additive health risk of cannabis and tobacco co-use.

PubMed

Meier, Ellen; Hatsukami, Dorothy K

2016-09-01

Cannabis and tobacco are the most widely used substances, and are often used together. The present review examines the toxicant exposure associated with co-use (e.g., carbon monoxide, carcinogens), co-use via electronic nicotine delivery systems (ENDS), and problematic methodological issues present across co-use studies. An extensive literature search through PubMed was conducted and studies utilizing human subjects and in vitro methods were included. Keywords included tobacco, cigarette, e-cigarette, ENDS, smoking, or nicotine AND marijuana OR cannabis OR THC. Co-use may pose additive risk for toxicant exposure as certain co-users (e.g., blunt users) tend to have higher breath carbon monoxide levels and cannabis smoke can have higher levels of some carcinogens than tobacco smoke. Cannabis use via ENDS is low and occurs primarily among established tobacco or cannabis users, but its incidence may be increasing and expanding to tobacco/cannabis naïve individuals. There are several methodological issues across co-use research including varying definitions of co-use, sample sizes, lack of control for important covariates (e.g., time since last cigarette), and inconsistent measurement of outcome variables. There are some known additive risks for toxicant exposure as a result of co-use. Research utilizing consistent methodologies is needed to further establish the additive risk of co-use. Future research should also be aware of novel technologies (e.g., ENDS) as they likely alter some toxicant exposure when used alone and with cannabis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Toxic exposure in America: estimating fetal and infant health outcomes from 14 years of TRI reporting.

PubMed

Agarwal, Nikhil; Banternghansa, Chanont; Bui, Linda T M

2010-07-01

We examine the effect of exposure to a set of toxic pollutants that are tracked by the Toxic Release Inventory (TRI) from manufacturing facilities on county-level infant and fetal mortality rates in the United States between 1989 and 2002. Unlike previous studies, we control for toxic pollution from both mobile sources and non-TRI reporting facilities. We find significant adverse effects of toxic air pollution concentrations on infant mortality rates. Within toxic air pollutants we find that releases of carcinogens are particularly problematic for infant health outcomes. We estimate that the average county-level decreases in various categories of TRI concentrations saved in excess of 13,800 infant lives from 1989 to 2002. Using the low end of the range for the value of a statistical life that is typically used by the EPA of $1.8M, the savings in lives would be valued at approximately $25B.

Proper interpretation of chronic toxicity studies and their statistics: A critique of "Which level of evidence does the US National Toxicology Program provide? Statistical considerations using the Technical Report 578 on Ginkgo biloba as an example".

PubMed

Kissling, Grace E; Haseman, Joseph K; Zeiger, Errol

2015-09-02

A recent article by Gaus (2014) demonstrates a serious misunderstanding of the NTP's statistical analysis and interpretation of rodent carcinogenicity data as reported in Technical Report 578 (Ginkgo biloba) (NTP, 2013), as well as a failure to acknowledge the abundant literature on false positive rates in rodent carcinogenicity studies. The NTP reported Ginkgo biloba extract to be carcinogenic in mice and rats. Gaus claims that, in this study, 4800 statistical comparisons were possible, and that 209 of them were statistically significant (p<0.05) compared with 240 (4800×0.05) expected by chance alone; thus, the carcinogenicity of Ginkgo biloba extract cannot be definitively established. However, his assumptions and calculations are flawed since he incorrectly assumes that the NTP uses no correction for multiple comparisons, and that significance tests for discrete data operate at exactly the nominal level. He also misrepresents the NTP's decision making process, overstates the number of statistical comparisons made, and ignores the fact that the mouse liver tumor effects were so striking (e.g., p<0.0000000000001) that it is virtually impossible that they could be false positive outcomes. Gaus' conclusion that such obvious responses merely "generate a hypothesis" rather than demonstrate a real carcinogenic effect has no scientific credibility. Moreover, his claims regarding the high frequency of false positive outcomes in carcinogenicity studies are misleading because of his methodological misconceptions and errors. Published by Elsevier Ireland Ltd.

Proper interpretation of chronic toxicity studies and their statistics: A critique of “Which level of evidence does the US National Toxicology Program provide? Statistical considerations using the Technical Report 578 on Ginkgo biloba as an example”

PubMed Central

Kissling, Grace E.; Haseman, Joseph K.; Zeiger, Errol

2014-01-01

A recent article by Gaus (2014) demonstrates a serious misunderstanding of the NTP’s statistical analysis and interpretation of rodent carcinogenicity data as reported in Technical Report 578 (Ginkgo biloba) (NTP 2013), as well as a failure to acknowledge the abundant literature on false positive rates in rodent carcinogenicity studies. The NTP reported Ginkgo biloba extract to be carcinogenic in mice and rats. Gaus claims that, in this study, 4800 statistical comparisons were possible, and that 209 of them were statistically significant (p<0.05) compared with 240 (4800 × 0.05) expected by chance alone; thus, the carcinogenicity of Ginkgo biloba extract cannot be definitively established. However, his assumptions and calculations are flawed since he incorrectly assumes that the NTP uses no correction for multiple comparisons, and that significance tests for discrete data operate at exactly the nominal level. He also misrepresents the NTP’s decision making process, overstates the number of statistical comparisons made, and ignores that fact that that the mouse liver tumor effects were so striking (e.g., p<0.0000000000001) that it is virtually impossible that they could be false positive outcomes. Gaus’ conclusion that such obvious responses merely “generate a hypothesis” rather than demonstrate a real carcinogenic effect has no scientific credibility. Moreover, his claims regarding the high frequency of false positive outcomes in carcinogenicity studies are misleading because of his methodological misconceptions and errors. PMID:25261588

[Research progress of health effect of polybrominated diphenyl ethers].

PubMed

Zhai, J X; Tong, S L

2016-06-01

Polybrominated diphenyl ethers (PBDEs) was one of the most common brominated flame retardants, it has been widely used in products such as furnitures, polymer and plastical material, textiles, electronic products and building materials. PBDEs have potential effect such as neurodevelopmental toxicity, reproductive toxicity, thyroid toxicity, immunological toxicity, embryo toxicity, liver toxicity, teratogenicity and potential carcinogenicity. This paper was aimed to review the environmental exposure way, current level, neurotoxicity, neurodevelopmental toxicity and reproductive toxicity of PBDEs. In recent years, PBDEs has been detected in environment, wildlife animal and human body around the world, there were the significant differences of exposure levels of PBDEs. The most abundant congener were tetra-BDE or BDE-47, hexa-BDE or BDE-153, and deca-BDE or BDE-209. Prenatal exposure to PBDEs has great impact on the infants' neurodevelopmental function, induces changes in neuropsychological developmental behavior, decreases of congnition, motivation and attention. High levels of PBDEs have positive relationship with Luteinizing hormone levels, testis disfunction and children's cryptorchidism, and have negative relationship with sperm number and testis size.

Databases applicable to quantitative hazard/risk assessment-Towards a predictive systems toxicology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Waters, Michael; Jackson, Marcus

2008-11-15

The Workshop on The Power of Aggregated Toxicity Data addressed the requirement for distributed databases to support quantitative hazard and risk assessment. The authors have conceived and constructed with federal support several databases that have been used in hazard identification and risk assessment. The first of these databases, the EPA Gene-Tox Database was developed for the EPA Office of Toxic Substances by the Oak Ridge National Laboratory, and is currently hosted by the National Library of Medicine. This public resource is based on the collaborative evaluation, by government, academia, and industry, of short-term tests for the detection of mutagens andmore » presumptive carcinogens. The two-phased evaluation process resulted in more than 50 peer-reviewed publications on test system performance and a qualitative database on thousands of chemicals. Subsequently, the graphic and quantitative EPA/IARC Genetic Activity Profile (GAP) Database was developed in collaboration with the International Agency for Research on Cancer (IARC). A chemical database driven by consideration of the lowest effective dose, GAP has served IARC for many years in support of hazard classification of potential human carcinogens. The Toxicological Activity Profile (TAP) prototype database was patterned after GAP and utilized acute, subchronic, and chronic data from the Office of Air Quality Planning and Standards. TAP demonstrated the flexibility of the GAP format for air toxics, water pollutants and other environmental agents. The GAP format was also applied to developmental toxicants and was modified to represent quantitative results from the rodent carcinogen bioassay. More recently, the authors have constructed: 1) the NIEHS Genetic Alterations in Cancer (GAC) Database which quantifies specific mutations found in cancers induced by environmental agents, and 2) the NIEHS Chemical Effects in Biological Systems (CEBS) Knowledgebase that integrates genomic and other biological data including dose-response studies in toxicology and pathology. Each of the public databases has been discussed in prior publications. They will be briefly described in the present report from the perspective of aggregating datasets to augment the data and information contained within them.« less

E-cigarettes in ENT: what do we need to know?

PubMed

Stobbs, N; Lillis, A; Kumar, N

2016-06-01

E-cigarette use in the UK is increasing and we are commonly encountering patients in the ENT clinic who are e-cigarette smokers. Currently, there is no regulatory body or licensing for e-cigarettes. This means that the contents, and therefore potential carcinogenic and toxic risks, can vary greatly from product to product. Patients are starting to ask about the risks of e-cigarettes and their use in smoking cessation. This review aimed to examine the regulations, trends, and carcinogenic and health risks of e-cigarettes, and summarise the evidence for their use in smoking cessation. It also aimed to provide a general awareness regarding the advice and information that can be safely given to patients.

Carcinogenicity and mode of action evaluation for alpha-hexachlorocyclohexane: Implications for human health risk assessment.

PubMed

Bradley, Ann E; Shoenfelt, Joanna L; Durda, Judi L

2016-04-01

Alpha-hexachlorocyclohexane (alpha-HCH) is one of eight structural isomers that have been used worldwide as insecticides. Although no longer produced or used agriculturally in the United States, exposure to HCH isomers is of continuing concern due to legacy usage and persistence in the environment. The U.S. Environmental Protection Agency (EPA) classifies alpha-HCH as a probable human carcinogen and provides a slope factor of 6.3 (mg/kg-day)(-1) for the compound, based on hepatic nodules and hepatocellular carcinomas observed in male mice and derived using a default linear approach for modeling carcinogens. EPA's evaluation, last updated in 1993, does not consider more recently available guidance that allows for the incorporation of mode of action (MOA) for determining a compound's dose-response. Contrary to the linear approach assumed by EPA, the available data indicate that alpha-HCH exhibits carcinogenicity via an MOA that yields a nonlinear, threshold dose-response. In our analysis, we conducted an MOA evaluation and dose-response analysis for alpha-HCH-induced liver carcinogenesis. We concluded that alpha-HCH causes liver tumors in rats and mice through an MOA involving increased promotion of cell growth, or mitogenesis. Based on these findings, we developed a threshold, cancer-based, reference dose (RfD) for alpha-HCH. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Health effects research in direct coal liquefaction. Studies of H-coal distillates: Phase I. PDU samples - the effects of hydrotreatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Epler, J.L.; Fry, R.J.M.; Larimer, F.W.

1981-11-01

A multi-divisional effort aimed at the integrated assessment of the health and environmental effects of various coal conversion and shale oil technologies is being carried out. The feasibility of using health effects bioassays to predict the potential biohazard of various H-Coal derived test materials is examined in a coupled chemical and biological approach. The primary focus of the research is the use of preliminary chemical characterizations and preparation for bioassay, followed by testing in short-term assays in order to rapidly ascertain the potential biohazard. Mammalian toxicological assays parallel the testing. Raw and hydrotreated product liquids from process development units ofmore » H-Coal and the pilot plant solvent refined coal process were examined for acute toxicity monitored as population growth impairment of Tetrahymena exposed to aqueous extracts and for mutagenic activity monitored as revertants of Salmonella exposed to metabolically activated chemical class fractions. Medium to high severity hydrotreatment appears to be an effective means of reducing biological activity, presumably by reducing the aromaticity and heteroatom content. Five basic mammalian, acute toxicity tests have been conducted with selected H-coal samples and shale oil derivatives. The data show that H-Coal samples are moderately toxic whereas the toxicity of shale oil derived products is slight and comparable to samples obtained from naturally occurring petroleums. No overt skin or eye toxicity was found. The present data reveal that coal-derived distillates generated by the H-coal process are highly carcinogenic to mouse skin. An extreme form of neurotoxicity associated with dermal exposure to one of the lighter, minimally carcinogenic, materials was noted. (DMC)« less

Trapping of cis-2-butene-1,4-dial to measure furan metabolism in human liver microsomes by cytochrome P450 enzymes.

PubMed

Gates, Leah A; Lu, Ding; Peterson, Lisa A

2012-03-01

Furan is a liver toxicant and carcinogen in rodents. It is classified as a possible human carcinogen, but the human health effects of furan exposure remain unknown. The oxidation of furan by cytochrome P450 (P450) enzymes is necessary for furan toxicity. The product of this reaction is the reactive α,β-unsaturated dialdehyde, cis-2-butene-1,4-dial (BDA). To determine whether human liver microsomes metabolize furan to BDA, a liquid chromatography/tandem mass spectrometry method was developed to detect and quantify BDA by trapping this reactive metabolite with N-acetyl-l-cysteine (NAC) and N-acetyl-l-lysine (NAL). Reaction of NAC and NAL with BDA generates N-acetyl-S-[1-(5-acetylamino-5-carboxypentyl)-1H-pyrrol-3-yl]-l-cysteine (NAC-BDA-NAL). Formation of NAC-BDA-NAL was quantified in 21 different human liver microsomal preparations. The levels of metabolism were comparable to that observed in F-344 rat and B6C3F1 mouse liver microsomes, two species known to be sensitive to furan-induced toxicity. Studies with recombinant human liver P450s indicated that CYP2E1 is the most active human liver furan oxidase. The activity of CYP2E1 as measured by p-nitrophenol hydroxylase activity was correlated to the extent of NAC-BDA-NAL formation in human liver microsomes. The formation of NAC-BDA-NAL was blocked by CYP2E1 inhibitors but not other P450 inhibitors. These results suggest that humans are capable of oxidizing furan to its toxic metabolite, BDA, at rates comparable to those of species sensitive to furan exposure. Therefore, humans may be susceptible to furan's toxic effects.

Trapping of cis-2-Butene-1,4-dial to Measure Furan Metabolism in Human Liver Microsomes by Cytochrome P450 Enzymes

PubMed Central

Gates, Leah A.; Lu, Ding

2012-01-01

Furan is a liver toxicant and carcinogen in rodents. It is classified as a possible human carcinogen, but the human health effects of furan exposure remain unknown. The oxidation of furan by cytochrome P450 (P450) enzymes is necessary for furan toxicity. The product of this reaction is the reactive α,β-unsaturated dialdehyde, cis-2-butene-1,4-dial (BDA). To determine whether human liver microsomes metabolize furan to BDA, a liquid chromatography/tandem mass spectrometry method was developed to detect and quantify BDA by trapping this reactive metabolite with N-acetyl-l-cysteine (NAC) and N-acetyl-l-lysine (NAL). Reaction of NAC and NAL with BDA generates N-acetyl-S-[1-(5-acetylamino-5-carboxypentyl)-1H-pyrrol-3-yl]-l-cysteine (NAC-BDA-NAL). Formation of NAC-BDA-NAL was quantified in 21 different human liver microsomal preparations. The levels of metabolism were comparable to that observed in F-344 rat and B6C3F1 mouse liver microsomes, two species known to be sensitive to furan-induced toxicity. Studies with recombinant human liver P450s indicated that CYP2E1 is the most active human liver furan oxidase. The activity of CYP2E1 as measured by p-nitrophenol hydroxylase activity was correlated to the extent of NAC-BDA-NAL formation in human liver microsomes. The formation of NAC-BDA-NAL was blocked by CYP2E1 inhibitors but not other P450 inhibitors. These results suggest that humans are capable of oxidizing furan to its toxic metabolite, BDA, at rates comparable to those of species sensitive to furan exposure. Therefore, humans may be susceptible to furan's toxic effects. PMID:22187484

Acute and long-term in vitro effects of zinc oxide nanoparticles.

PubMed

Annangi, Balasubramanyam; Rubio, Laura; Alaraby, Mohamed; Bach, Jordi; Marcos, Ricard; Hernández, Alba

2016-09-01

Since most of the toxic studies of zinc oxide nanoparticles (ZnO NPs) focused on acute and high-dose exposure conditions, the aim of the present study was to fill the existing knowledge gap of long-term effects of ZnO NPs at sub-toxic doses. To overcome this point, we have evaluated the toxic, genotoxic, and carcinogenic effects of ZnO NPs under long-term treatments (12 weeks), using a sub-toxic dose (1 µg/mL) according to acute 48-h exposure. Preliminarily, oxidative stress and genotoxic/oxidative DNA damage were determined under acute exposure and high-dose conditions. To determine the role of oxidative DNA damage, a wild-type mouse embryonic fibroblast (MEF Ogg1 (+/+)) and its isogenic 8-oxo-guanine DNA glycosylase 1 (Ogg1) knockout partner (MEF Ogg1 (-/-)) cell lines were used. Although short-term exposure (24-h) experiments demonstrated that ZnO NPs were able to induce ROS, genotoxicity, and oxidative DNA damage in both cell lines, no effects were obtained under long-term exposure scenario. Thus, 1 µg/mL exposure over 12 weeks was unable to induce genotoxicity as well as cellular transformation in both cell types, as indicated by the lack of observed morphological cell changes, variations in the secretion of matrix metalloproteinases, and anchorage-independent cell growth ability, regarded as cancer-like phenotypic hallmarks. Our results indicate that short-term effects of ZnO NP exposure are not replicated under long-term and sub-toxic dose conditions. All together, the lack of genotoxic/carcinogenic effects after chronic treatments seem to indicate a reduced risk associated with ZnO NP exposure.

Ptaquiloside, the major carcinogen of bracken fern, in the pooled raw milk of healthy sheep and goats: an underestimated, global concern of food safety.

PubMed

Virgilio, Antonella; Sinisi, Annamaria; Russo, Valeria; Gerardo, Salvatore; Santoro, Adriano; Galeone, Aldo; Taglialatela-Scafati, Orazio; Roperto, Franco

2015-05-20

Bracken fern (Pteridium aquilinum) is a worldwide plant containing toxic substances, which represent an important chemical hazard for animals, including humans. Ptaquiloside, 1, a norsesquiterpenoid glucoside, is the major carcinogen of bracken detected in the food chain, particularly in the milk from farm animals. To date, ptaquiloside has been shown in the milk of cows feeding on a diet containing bracken fern. This is the first study that shows the systematic detection of ptaquiloside, 1, and reports its direct quantitation in pooled raw milk of healthy sheep and goats grazing on bracken. Ptaquiloside, 1, was detected by a sensitive method based on the chemical conversion of ptaquiloside, 1, into bromopterosine, 4, following gas chromatography-mass spectrometry (GC-MS) analysis. The presence of ptaquiloside, 1, possibly carcinogenic to humans, in the milk of healthy animals is an unknown potential health risk, thus representing a harmful and potential global concern of food safety.

A Literature Review-Problem Definition Studies on Selected Toxic Chemicals. Volume 1. Occupational Health and Safety Aspects of Diesel Fuel and White Smoke Generated from It

DTIC Science & Technology

1978-04-01

properties heating oil :mammalian toxicity sampling ABSTRACT (Cotthum an to~" aid* if neoe...m mE ide .Ids bp block ,ninborj Literature is reviewed (75...mutations. Diesel fuel may be excreted from the body in the urine , or exhaled from the lungs. Persons who may be exposed to diesel fuel white smoke should be...37 VIII. Carcinogenicity, Mutagenicity, Teratogenicity 42 IX. Industrial Hygiene Practices and Standards 43 X. Sampling and Analytic Techniques 45

Pyrrolizidine alkaloid-containing toxic plants (Scenecio, Crotalaria, Cynoglossum, Amsinckia, Heliotropium, and Echium spp.)

USDA-ARS?s Scientific Manuscript database

Pyrrolizidine alkaloid (PA) containing plants are found throughout the world and are probably the most common plant cause of poisoning of livestock, wildlife and humans. PAs are potent liver toxins that under some conditions can be carcinogenic. The objective of this paper is to briefly introduce hi...

Ptaquiloside reduces NK cell activities by enhancing metallothionein expression, which is prevented by selenium

USDA-ARS?s Scientific Manuscript database

Pteridium aquilinum, one of the most important poisonous plants in the world, is known to be carcinogenic to animals and humans. Moreover, our previous studies showed that the immunosuppressive effects of ptaquiloside, its main toxic agent, were prevented by selenium in mouse natural killer (NK) cel...

p-Nitrophenol and glutathione response in medaka (Oryzias latipes)exposed to MX, a drinking water carcinogen

EPA Science Inventory

When chlorine is introduced into public drinking water for disinfection, it can react with organic compounds in surface waters to form toxic by-products such as 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-furanone (MX). We investigated the effect of exposure to MX on cytochrome ...

The master transcription factor mtfA governs aflatoxin production, morphological development, and pathogenicity in the fungus Aspergillus flavus

USDA-ARS?s Scientific Manuscript database

Aspergillus flavus produces a variety of toxic secondary metabolites, among them the aflatoxins (AFs) are the most well-known. These compounds are highly mutagenic and carcinogenic, particularly AFB1. A. flavus is capable of colonizing economically important crops contaminating them with AFs. Molecu...

P-NITROPHENOL AND GLUTATHIONE RESPONSE IN MEDAKA (ORYZIAS LATIPES) EXPOSED TO MX, A DRINKING WATER CARCINOGEN.

EPA Science Inventory

When chlorine is introduced into public drinking water for disinfection, it can react with organic compounds in surface waters to form toxic by-products such as 3-chloro-4- (dichloromethyl)-5-hydroxy-2[5H]-furanone (MX). We investigated the effect of exposure to MX on cytochr...

EFFECTS OF 1,3-BUTADIENE, ISOPRENE, AND THEIR PHOTOCHEMICAL DEGRADATION PRODUCTS ON HUMAN LUNG CELLS

EPA Science Inventory

Because of potential exposure both in the workplace and from ambient air, the known carcinogen 1,3-butadiene (BD) is considered a priority hazardous air pollutant. BD and its 2-methyl analog, isoprene (ISO), are chemically similar but have very different toxicities, with ISO show...

Metabolic and genomic analysis elucidates strain-level variation in Microbacterium spp. isolated from chromate contaminated sediment

EPA Science Inventory

Hexavalent chromium [Cr(VI)], a soluble carcinogen, has caused widespread contamination of soil and water in many industrial nations. Bacteria have been shown to play an active role in the reduction of Cr(VI) to Cr(III), which is insoluble and less toxic, however, the biological ...

Analysis of the Aspergillus flavus transcriptome reveals a key role of secondary metabolite production in isolate oxidative stress responses

USDA-ARS?s Scientific Manuscript database

The purpose of the production of secondary metabolites in fungi are various and include stress responses, competitive antimicrobial activity, and the elimination of toxic compounds. However, the purpose of the production of aflatoxin, a carcinogenic mycotoxin, by Aspergillus flavus, is unknown. Prev...

The comparative toxicity of a reduced, crude comfrey (Symphytum officinale) alkaloid extract and the pure, comfrey-derived pyrrolizidine alkaloids, lycopsamine and intermedine in chicks (Gallus gallus domesticus)

USDA-ARS?s Scientific Manuscript database

Comfrey (Symphytum officinale), a commonly used herb, contains dehydropyrrolizidine alkaloids (DHPAs) that, as a group of bioactive metabolites, are potentially hepatotoxic, pneumotoxic, genotoxic and carcinogenic. Consequently, regulatory agencies and international health organizations have recomm...

First Report of an Atypical New Aspergillus parasiticus Isolates with Nucleotides Insertion in aflR Gene Identical to Aspergillus sojae

USDA-ARS?s Scientific Manuscript database

Aflatoxins are toxic and carcinogenic secondary metabolites produced primarily by the filamentous fungi Aspergillus favus and Aspergillus parasitic and cause toxin contamination in food chain worldwide. Aspergillus oryzae and Aspergillus sojae are highly valued as koji molds in the traditional prep...

Evaluation of the expression of genes associated with resistance to Aspergillus flavus colonization and aflatoxin production in different maize lines

USDA-ARS?s Scientific Manuscript database

Aflatoxins are carcinogenic toxic compounds produced by Aspergillus flavus during infection of crops including maize (Zea mays L.). Contamination of maize with aflatoxin is exacerbated by late season drought stress. Previous studies have implicated numerous resistance-associated proteins (RAPs) that...

EMERGING TECHNOLOGY REPORT: CROSS-FLOW PERVAPORATION SYSTEM FOR REMOVAL OF VOCS FROM CONTAMINATED WASTEWATER

EPA Science Inventory

The U.S. Federal Register of April 17, 1987, contains a list of priority pollutants found at Superfund sites. bout half of these are volatile organic compounds (VOCs), which are known to be toxic and/or carcinogenic in nature. ervaporation is a membrane technology utilizing a den...

Occurrence and risk assessment of potentially toxic elements and typical organic pollutants in contaminated rural soils.

PubMed

Xu, Yongfeng; Dai, Shixiang; Meng, Ke; Wang, Yuting; Ren, Wenjie; Zhao, Ling; Christie, Peter; Teng, Ying

2018-07-15

The residual levels and risk assessment of several potentially toxic elements (PTEs), phthalate esters (PAEs) and polycyclic aromatic hydrocarbons (PAHs) in rural soils near different types of pollution sources in Tianjin, China, were studied. The soils were found to be polluted to different extents with PTEs, PAEs and PAHs from different pollution sources. The soil concentrations of chromium (Cr), nickel (Ni), di-n-butyl phthalate (DnBP), acenaphthylene (Any) and acenaphthene (Ane) were higher than their corresponding regulatory reference limits. The health risk assessment model used to calculate human exposure indicates that both non-carcinogenic and carcinogenic risks from selected pollutants were generally acceptable or close to acceptable. Different types of pollution sources and soil physicochemical properties substantially affected the soil residual concentrations of and risks from these pollutants. PTEs in soils collected from agricultural lands around industrial and residential areas and organic pollutants (PAEs and PAHs) in soils collected from agricultural areas around livestock breeding were higher than those from other types of pollution sources and merit long-term monitoring. Copyright © 2018 Elsevier B.V. All rights reserved.

The toxic effects of flame retardants: a gene expression study in elucidating their carcinogenicity

NASA Astrophysics Data System (ADS)

Vagula, Mary; Al-Dhumani, Ali; Al-Dhumani, Sajaad; Mastro, Alexandra

2013-05-01

Polybrominated Diphenyl Ethers (PBDEs) are flame retardants widely used in many commercial products, including building materials, electronics, furnishings, motor vehicles, airplanes, plastics, polyurethane foams, and textiles. Although the specific toxic action of these chemicals is not clear, it is reported that they can cause serious damage to the nervous, reproductive, and endocrine systems. These chemicals are branded as "probable carcinogens" by Environmental Protection Agency (EPA). Therefore, this study is taken up to investigate the expression of genes namely, TP-53, RAD1, CRADD, and ATM, which are involved in apoptosis, DNA repair and cell cycle regulation. For this study human umbilical vein endothelial cells (HUVEC) are exposed to 5 μM of BDE-85 (a penta-BDE) and BDE-209 (deca-BDE). The results of this report reveal significant alteration in all the genes under investigation in BDE-85 and BDE-209 exposed cells. The BDE-85 induced responses are significantly more than BDE-209. These results emphasize the congener specific action of PBDEs on the expression of genes relevant to DNA repair and cell division of HUVEC cells.

Consumer hazards of plastics.

PubMed Central

Wiberg, G S

1976-01-01

The modern consumer is exposed to a wide variety of plastic and rubber products in his day to day life: at home, work, school, shopping, recreation and play, and transport. A large variety of toxic sequellae have resulted from untoward exposures by many different routes: oral, dermal, inhalation, and parenteral. Toxic change may result from the plastic itself, migration of unbound components and additives, chemical decomposition or toxic pyrolysis products. The type of damage may involve acute poisoning, chronic organ damage, reproductive disorders, and carcinogenic, mutagenic and teratogenic episodes. Typical examples for all routes are cited along with the activites of Canadian regulatory agencies to reduce both the incidence and severity of plastic-induced disease. PMID:1026409

Immunosuppression by hypoxic cell radiosensitizers: a phenomenon of potential clinical importance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rockwell, S.; Kapp, D.S.

1982-06-01

The nitroimidazoles metronidazole, misonidazol, and desmethyl misonidazole are currently undergoing clinical trials as possible adjuncts to radiotherapy. Ongoing clinical trials are evaluating the effectiveness of these agents and also documenting the pharmacokinetics and toxicities of radiosensitizing doses of these drugs in man. A variety of toxic effects have been noted in man, including anorexia, nausea and vomiting, peripheral neuropathy, central nervous system symptoms, ototoxicity, allergy, and fear. Laboratory studies have also suggested that these agents have potential to be mutagenic, carcinogenic, and teratogenic. In the editorial presented, the author attempts to draw attention to an additional toxic effect of nitroimidazolesmore » - the inhibition of cell-mediated immune responses. (JMT)« less

Division of Biological and Medical Research annual research summary, 1983

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barr, S.H.

1984-08-01

This research summary contains brief descriptions of research in the following areas: (1) mechanisms of hepatocarcinogenesis; (2) role of metals in cocarcinogenesis and the use of liposomes for metal mobilization; (3) control of mutagenesis and cell differentiation in cultured cells by tumor promoters; (4) radiation effects in mammalian cells; (5) radiation carcinogenesis and radioprotectors; (6) life shortening, tumor induction, and tissue dose for fission-neutron and gamma-ray irradiations; (7) mammalian genetics and biostatistics; (8) radiation toxicity studies; (9) hematopoiesis in chronic toxicity; (10) molecular biology studies; (11) chemical toxicology; (12) carcinogen identification and metabolism; (13) metal metabolism and toxicity; and (14)more » neurobehavioral chronobiology. (ACR)« less

Chemical and toxicological characteristics of conventional and low-TSNA moist snuff tobacco products.

PubMed

Song, Min-Ae; Marian, Catalin; Brasky, Theodore M; Reisinger, Sarah; Djordjevic, Mirjana; Shields, Peter G

2016-03-14

Use of smokeless tobacco products (STPs) is associated with oral cavity cancer and other health risks. Comprehensive analysis for chemical composition and toxicity is needed to compare conventional and newer STPs with lower tobacco-specific nitrosamines (TSNAs) yields. Seven conventional and 12 low-TSNA moist snuff products purchased in the U.S., Sweden, and South Africa were analyzed for 18 chemical constituents (International Agency for Research on Cancer classified carcinogens), pH, nicotine, and free nicotine. Chemicals were compared in each product using Wilcoxon rank-sum test and principle component analysis (PCA). Conventional compared to low-TSNA moist snuff products had higher ammonia, benzo[a]pyrene, cadmium, nickel, nicotine, nitrate, and TSNAs and had lower arsenic in dry weight content and per mg nicotine. Lead and chromium were significantly higher in low-TSNA moist snuff products. PCA showed a clear difference for constituents between conventional and low-TSNA moist snuff products. Differences among products were reduced when considered on a per mg nicotine basis. As one way to contextualize differences in constituent levels, probabilistic lifetime cancer risk was estimated for chemicals included in The University of California's carcinogenic potency database (CPDB). Estimated probabilistic cancer risks were 3.77-fold or 3-fold higher in conventional compared to low-TSNA moist snuff products under dry weight or under per mg nicotine content, respectively. In vitro testing for the STPs indicated low level toxicity and no substantial differences. The comprehensive chemical characterization of both conventional and low-TSNA moist snuff products from this study provides a broader assessment of understanding differences in carcinogenic potential of the products. In addition, the high levels and probabilistic cancer risk estimates for certain chemical constituents of smokeless tobacco products will further inform regulatory decision makers and aid them in their efforts to reduce carcinogen exposure in smokeless tobacco products. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

2-Phenethyl Isothiocyanate, Glutathione S-transferase M1 and T1 Polymorphisms, and Detoxification of Volatile Organic Carcinogens and Toxicants in Tobacco Smoke.

PubMed

Yuan, Jian-Min; Murphy, Sharon E; Stepanov, Irina; Wang, Renwei; Carmella, Steven G; Nelson, Heather H; Hatsukami, Dorothy; Hecht, Stephen S

2016-07-01

Cigarette smoke contains relatively large quantities of volatile organic toxicants or carcinogens such as benzene, acrolein, and crotonaldehyde. Among their detoxification products are mercapturic acids formed from glutathione conjugation, catalyzed in part by glutathione S-transferases (GST). A randomized phase II clinical trial with a crossover design was conducted to evaluate the effect of 2-phenethyl isothiocyanate (PEITC), a natural product formed from gluconasturtiin in certain cruciferous vegetables, on the detoxification of benzene, acrolein, and crotonaldehyde in 82 cigarette smokers. Urinary mercapturic acids of benzene, acrolein, and crotonaldehyde at baseline and during treatment were quantified. Overall, oral PEITC supplementation increased the mercapturic acid formed from benzene by 24.6% (P = 0.002) and acrolein by 15.1% (P = 0.005), but had no effect on crotonaldehyde. A remarkably stronger effect was observed among subjects with the null genotype of both GSTM1 and GSTT1: in these individuals, PEITC increased the detoxification metabolite of benzene by 95.4% (P < 0.001), of acrolein by 32.7% (P = 0.034), and of crotonaldehyde by 29.8% (P = 0.006). In contrast, PEITC had no effect on these mercapturic acids in smokers possessing both genes. PEITC had no effect on the urinary oxidative stress biomarker 8-iso-prostaglandin F2α or the inflammation biomarker prostaglandin E2 metabolite. This trial demonstrates an important role of PEITC in detoxification of environmental carcinogens and toxicants which also occur in cigarette smoke. The selective effect of PEITC on detoxification in subjects lacking both GSTM1 and GSTT1 genes supports the epidemiologic findings of stronger protection by dietary isothiocyanates against the development of lung cancer in such individuals. Cancer Prev Res; 9(7); 598-606. ©2016 AACR. ©2016 American Association for Cancer Research.

U.S. EPA'S RESEARCH TO UPDATE GUIDANCE FOR QUANTIFYING LANDFILL GAS EMISSIONS

EPA Science Inventory

Landfill emissions, if left uncontrolled, contribute to air toxics, climate change, tropospheric ozone, and urban smog. EPA's Office of Research and Development is conducting research to help update EPA's landfill gas emission factors. The last update to EPA's landfill gas emiss...

Tobacco Product Waste: An Environmental Approach to Reduce Tobacco Consumption.

PubMed

Novotny, Thomas E; Slaughter, Elli

2014-01-01

Cigarette butts and other tobacco product wastes (TPW) are the most common items picked up in urban and beach cleanups worldwide. TPW contains all the toxins, nicotine, and carcinogens found in tobacco products, along with the plastic nonbiodegradable filter attached to almost all cigarettes sold in the United States and in most countries worldwide. Toxicity studies suggest that compounds leached from cigarette butts in salt and fresh water are toxic to aquatic micro-organisms and test fish. Toxic chemicals have also been identified in roadside TPW. With as much as two-thirds of all smoked cigarettes (numbering in the trillions globally) being discarded into the environment each year, it is critical to consider the potential toxicity and remediation of these waste products. This article reviews reports on the toxicity of TPW and recommends several policy approaches to mitigation of this ubiquitous environmental blight.

NTP technical report on toxicity studies of cadmium oxide (Cas No. 1306-19-0) administered by inhalation to F344/N rats and B6C3f1 mice. Toxicity report series

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1995-03-01

Three thousand tons of cadmium are imported or produced annually in the United States, and approximately 90% of this is cadmium oxide. Cadmium oxide is used in batteries, electroplating baths, pigments, plastics, synthetic products, and a variety of other materials. Cadmium oxide was nominated for study by the National Cancer Institute because of its widespread use and to obtain toxicity and carcinogenicity information. This report describes toxicity studies of cadmium oxide aerosol in F344/N rats and B6C3F1 mice, including sperm motility and vaginal cytology evaluations, and developmental toxicity studies of cadmium oxide aerosol in Sprague-Dawley rats and Swiss (CD-1) mice.more » Genetic toxicology studies were done in Salmonella typhimurium and B6C3F1 mice erythrocytes.« less

Report of the Federal Panel on Formaldehyde.

PubMed Central

1982-01-01

The Federal Panel on Formaldehyde concluded that definitive experiments exist which demonstrate the mutagenicity and carcinogenicity of formaldehyde under laboratory conditions. Formaldehyde induces both gene mutations and chromosomal aberrations in a variety of test systems. Inhalation of formaldehyde causes cancer of the nose in rats. The concentrations of formaldehyde in inhaled air that caused nasal cancer in Fisher 344 rats are within the same order of magnitude as those to which humans may be exposed. The data presently available do not permit a direct assessment of the carcinogenicity of formaldehyde to man. Epidemiologic studies on exposed human populations are in progress and may further clarify the situation. Other experimental and human studies on toxic effects such as teratogenicity and reproductive disorders are as yet inadequate for a health risk assessment. The CIIT 24 month study on animal carcinogenicity has not yet been completely evaluated. Additional data are expected on the effects of prolonged exposure to lower doses of formaldehyde and on the possible carcinogenicity of formaldehyde in the mouse. The panel recommends that, for a comprehensive health risk assessment, further experiments be conducted on the effects of other modes of exposure (ingestion and skin penetration), the effects in humans, and on the pharmacokinetics of formaldehyde in man and animals and the possible role for formaldehyde in reproductive and chronic respiratory disorders. It is the conclusion of the panel that formaldehyde should be presumed to pose a carcinogenic risk to humans. PMID:6977445

Asian Americans and disproportionate exposure to carcinogenic hazardous air pollutants: A national study.

PubMed

Grineski, Sara E; Collins, Timothy W; Morales, Danielle X

2017-07-01

Studies have demonstrated disparate exposures to carcinogenic hazardous air pollutants (HAPs) in neighborhoods with high densities of Black and Hispanic residents in the US. Asians are the fastest growing racial/ethnic group in the US, yet they have been underemphasized in previous studies of environmental health and injustice. This cross-sectional study investigated possible disparities in residential exposure to carcinogenic HAPs among Asian Americans, including Asian American subgroups in the US (including all 50 states and the District of Columbia, n = 71,208 US census tracts) using National Air Toxics Assessment and US Census data. In an unadjusted analysis, Chinese and Korean Americans experience the highest mean cancer risks from HAPs, followed by Blacks. The aggregated Asian category ranks just below Blacks and above Hispanics, in terms of carcinogenic HAP risk. Multivariate models adjusting for socioeconomic status, population density, urban location, and geographic clustering show that an increase in proportion of Asian residents in census tracts is associated with significantly greater cancer risk from HAPs. Neighborhoods with higher proportions (as opposed to lower proportions) of Chinese, Korean, and South Asian residents have significantly greater cancer risk burdens relative to Whites. Tracts with higher concentrations of Asians speaking a non-English language and Asians that are US-born have significantly greater cancer risk burdens. Asian Americans experience substantial residential exposure to carcinogenic HAPs in US census tracts and in the US more generally. Copyright © 2017 Elsevier Ltd. All rights reserved.

New perspectives in toxicological information management, and the role of ISSTOX databases in assessing chemical mutagenicity and carcinogenicity.

PubMed

Benigni, Romualdo; Battistelli, Chiara Laura; Bossa, Cecilia; Tcheremenskaia, Olga; Crettaz, Pierre

2013-07-01

Currently, the public has access to a variety of databases containing mutagenicity and carcinogenicity data. These resources are crucial for the toxicologists and regulators involved in the risk assessment of chemicals, which necessitates access to all the relevant literature, and the capability to search across toxicity databases using both biological and chemical criteria. Towards the larger goal of screening chemicals for a wide range of toxicity end points of potential interest, publicly available resources across a large spectrum of biological and chemical data space must be effectively harnessed with current and evolving information technologies (i.e. systematised, integrated and mined), if long-term screening and prediction objectives are to be achieved. A key to rapid progress in the field of chemical toxicity databases is that of combining information technology with the chemical structure as identifier of the molecules. This permits an enormous range of operations (e.g. retrieving chemicals or chemical classes, describing the content of databases, finding similar chemicals, crossing biological and chemical interrogations, etc.) that other more classical databases cannot allow. This article describes the progress in the technology of toxicity databases, including the concepts of Chemical Relational Database and Toxicological Standardized Controlled Vocabularies (Ontology). Then it describes the ISSTOX cluster of toxicological databases at the Istituto Superiore di Sanitá. It consists of freely available databases characterised by the use of modern information technologies and by curation of the quality of the biological data. Finally, this article provides examples of analyses and results made possible by ISSTOX.

Potentially toxic elements in soil of the Khyber Pakhtunkhwa province and Tribal areas, Pakistan: evaluation for human and ecological risk assessment.

PubMed

Saddique, Umar; Muhammad, Said; Tariq, Mohsin; Zhang, Hua; Arif, Mohammad; Jadoon, Ishtiaq A K; Khattak, Nimat Ullah

2018-03-22

Potentially toxic elements (PTEs) contaminations in the soil ecosystem are considered as extremely hazardous due to toxicity, persistence and bioaccumulative nature. Therefore, this study was aimed to summarize the results of published PTEs in soil of Khyber Pakhtunkhwa and Tribal areas, Pakistan. Results were evaluated for the pollution quantification factors, including contamination factor (CF), pollution load index (PLI), ecological risk index (ERI) and human health risk assessment. The highest CF (797) and PLI (7.35) values were observed for Fe and ERI (857) values for Cd. Soil PTEs concentrations were used to calculate the human exposure for the risk assessment, including chronic or non-carcinogenic risks such as the hazard quotient (HQ) and carcinogenic or cancer risk (CR). The values of HQ were > 1 for the Cd, Co and Cr in Khyber Pakhtunkhwa and Tribal areas. Tribal areas showed higher values of ERI, HQ, and CR as compared to the Khyber Pakhtunkhwa that were attributed to the mining activities, weathering and erosion of mafic and ultramafic bedrocks hosting ophiolites. This study strongly recommends that best control measures need to be taken for soil PTEs with the intent to alleviate any continuing potential threat to the human health, property and environment, which otherwise could enter ecosystem and ultimately the living beings. Further studies are recommended to combat the soil PTEs concentrations and toxicity in the Tribal areas for a best picture of understanding the element effects on human, and environment can be achieved that will lead to a sustainable ecological harmony.

Environmental complex mixture toxicity assessment.

PubMed

Gardner, H S; Brennan, L M; Toussaint, M W; Rosencrance, A B; Boncavage-Hennessey, E M; Wolfe, M J

1998-12-01

Trichloroethylene (TCE) was found as a contaminant in the well supplying water to an aquatic testing laboratory. The groundwater was routinely screened by a commercial laboratory for volatile and semivolatile compounds, metals, herbicides, pesticides, and polychlorinated biphenyls using U.S. Environmental Protection Agency methods. Although TCE was the only reportable peak on the gas chromatograph, with average concentrations of 0.200 mg/l, other small peaks were also present, indicating the possibility that the contamination was not limited to TCE alone. A chronic 6-month carcinogenicity assay was conducted on-site in a biomonitoring trailer, using the Japanese medaka fish (Oryzias latipes) in an initiation-promotion protocol, with diethylnitrosamine (DEN) as the initiator and the TCE-contaminated groundwater as a promoter. Study results indicated no evidence of carcinogenic potential of the groundwater without initiation. There was, however, a tumor-promotional effect of the groundwater after DEN initiation. A follow-up laboratory study was conducted using reagent grade TCE added to carbon-filtered groundwater to simulate TCE concentrations comparable to those found in the contaminated groundwater. Study results indicated no promotional effects of TCE. These studies emphasize the necessity for on-site bioassays to assess potential environmental hazards. In this instance, chemical analysis of the groundwater identified TCE as the only reportable contaminant, but other compounds present below reportable limits were noted and may have had a synergistic effect on tumor promotion observed with the groundwater exposure. Laboratory toxicity testing of single compounds can produce toxicity data specific to that compound for that species but cannot take into account the possible toxic effects of mixtures of compounds.

Differences in lung local dosimetry of the carcinogens benzo(a)pyrene and NNK

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dahl, A.R.; Muggenburg, B.A.; Thornton-Manning, J.R.

1996-12-31

A diffusion model predicts that highly lipophilic toxicants penetrate the comparatively thick epithelium of the conducting airways much more slowly than less lipophilic toxicants. To validate this model, the tracheal walls of a Beagle dog were sprayed with very small quantities of tritiated, highly lipophilic benzo(a)pyrene (BaP), moderately lipophilic pyrene, or slightly lipophilic 4-(methylnitrosamino)-1-(3 pyridyl)-1-butanone-(NNK). The concentration of the hydrocarbons and their metabolites were measured in the circulating blood for up to 6 hr, and tissue retention was determined at the end of the experiment. Differences in absorption of these compounds into blood were manifested in several independent measurements. Themore » highly lipophilic toxicant manifested: (1) a much slower penetration into azygous vein blood, the principal drainage system from the exposed area of the trachea; (2) a much slower appearance in the systemic circulation and (3) a much greater retention in the tracheal tissues at the end of the exposure. Increased retention mm in the airway mucosa allowed a grew fraction of lipophilic toxicants to be metabolized locally in the airway walls. This finding led us to conclude that, for example, if the carcinogens BaP and NNK are deposited at the same surface density on the airway mucosa, the highly lipophilic BaP will reach a far higher concentration in the airway epithelium than will the less lipophilic NNK. Such sharp differences in local dosimetry should be considered in order to improve the accuracy of risk assessment models for inhalants.« less

Biomonitoring Human Albumin Adducts: The Past, the Present, and the Future

PubMed Central

2016-01-01

Serum albumin (Alb) is the most abundant protein in blood plasma. Alb reacts with many carcinogens and/or their electrophilic metabolites. Studies conducted over 20 years ago showed that Alb forms adducts with the human carcinogens aflatoxin B1 and benzene, which were successfully used as biomarkers in molecular epidemiology studies designed to address the role of these chemicals in cancer risk. Alb forms adducts with many therapeutic drugs or their reactive metabolites such as β-lactam antibiotics, acetylsalicylic acid, acetaminophen, nonsteroidal anti-inflammatory drugs, chemotherapeutic agents, and antiretroviral therapy drugs. The identification and characterization of the adduct structures formed with Alb have served to understand the generation of reactive metabolites and to predict idiosyncratic drug reactions and toxicities. The reaction of candidate drugs with Alb is now exploited as part of the battery of screening tools to assess the potential toxicities of drugs. The use of gas chromatography-mass spectrometry, liquid chromatography, or liquid chromatography-mass spectrometry (LC-MS) enabled the identification and quantification of multiple types of Alb xenobiotic adducts in animals and humans during the past three decades. In this perspective, we highlight the history of Alb as a target protein for adduction to environmental and dietary genotoxicants, pesticides, and herbicides, common classes of medicinal drugs, and endogenous electrophiles, and the emerging analytical mass spectrometry technologies to identify Alb-toxicant adducts in humans. PMID:27989119

2,6-Dithiopurine blocks toxicity and mutagenesis in human skin cells exposed to sulfur mustard analogues, 2-chloroethyl ethyl sulfide and 2-chloroethyl methyl sulfide.

PubMed

Powell, K Leslie; Boulware, Stephen; Thames, Howard; Vasquez, Karen M; MacLeod, Michael C

2010-03-15

Sulfur mustard (bis-(2-chloroethyl)sulfide) is a well-known chemical warfare agent that induces debilitating cutaneous toxicity in exposed individuals. It is also known to be carcinogenic and mutagenic because of its ability to damage DNA via electrophilic attack. We previously showed that a nucleophilic scavenger, 2,6-dithiopurine (DTP), reacts chemically with several electrophilic carcinogens, blocking DNA damage in vitro and in vivo and abolishing tumor formation in a two-stage mouse skin carcinogenesis model. To assess the potential of DTP as an antagonist of sulfur mustard, we have utilized monofunctional chemical analogues of sulfur mustard, 2-chloroethyl ethyl sulfide (CEES) and 2-chloroethyl methyl sulfide (CEMS), to induce toxicity and mutagenesis in a cell line, NCTC2544, derived from a human skin tumor. We show that DTP blocks cytotoxicity in CEMS- and CEES-treated cells when present at approximately equimolar concentration. A related thiopurine, 9-methyl-6-mercaptopurine, is similarly effective. Correlated with this, we find that DTP is transported into these cells and that adducts between DTP and CEES are found intracellularly. Using a shuttle vector-based mutagenesis system, which allows enumeration of mutations induced in the skin cells by a blue/white colony screen, we find that DTP completely abolishes the mutagenesis induced by CEMS and CEES in human cells.

The fifth plot of the Carcinogenic Potency Database: results of animal bioassays published in the general literature through 1988 and by the National Toxicology Program through 1989.

PubMed Central

Gold, L S; Manley, N B; Slone, T H; Garfinkel, G B; Rohrbach, L; Ames, B N

1993-01-01

This paper is the fifth plot of the Carcinogenic Potency Database (CPDB) that first appeared in this journal in 1984 (1-5). We report here results of carcinogenesis bioassays published in the general literature between January 1987 and December 1988, and in technical reports of the National Toxicology Program between July 1987 and December 1989. This supplement includes results of 412 long-term, chronic experiments of 147 test compounds and reports the same information about each experiment in the same plot format as the earlier papers: the species and strain of test animal, the route and duration of compound administration, dose level and other aspects of experimental protocol, histopathology and tumor incidence, TD50 (carcinogenic potency) and its statistical significance, dose response, author's opinion about carcinogenicity, and literature citation. We refer the reader to the 1984 publications (1,5,6) for a guide to the plot of the database, a complete description of the numerical index of carcinogenic potency, and a discussion of the sources of data, the rationale for the inclusion of particular experiments and particular target sites, and the conventions adopted in summarizing the literature. The five plots of the database are to be used together, as results of individual experiments that were published earlier are not repeated. In all, the five plots include results of 4487 experiments on 1136 chemicals. Several analyses based on the CPDB that were published earlier are described briefly, and updated results based on all five plots are given for the following earlier analyses: the most potent TD50 value by species, reproducibility of bioassay results, positivity rates, and prediction between species.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8354183

Literature-based compound profiling: application to toxicogenomics.

PubMed

Frijters, Raoul; Verhoeven, Stefan; Alkema, Wynand; van Schaik, René; Polman, Jan

2007-11-01

To reduce continuously increasing costs in drug development, adverse effects of drugs need to be detected as early as possible in the process. In recent years, compound-induced gene expression profiling methodologies have been developed to assess compound toxicity, including Gene Ontology term and pathway over-representation analyses. The objective of this study was to introduce an additional approach, in which literature information is used for compound profiling to evaluate compound toxicity and mode of toxicity. Gene annotations were built by text mining in Medline abstracts for retrieval of co-publications between genes, pathology terms, biological processes and pathways. This literature information was used to generate compound-specific keyword fingerprints, representing over-represented keywords calculated in a set of regulated genes after compound administration. To see whether keyword fingerprints can be used for assessment of compound toxicity, we analyzed microarray data sets of rat liver treated with 11 hepatotoxicants. Analysis of keyword fingerprints of two genotoxic carcinogens, two nongenotoxic carcinogens, two peroxisome proliferators and two randomly generated gene sets, showed that each compound produced a specific keyword fingerprint that correlated with the experimentally observed histopathological events induced by the individual compounds. By contrast, the random sets produced a flat aspecific keyword profile, indicating that the fingerprints induced by the compounds reflect biological events rather than random noise. A more detailed analysis of the keyword profiles of diethylhexylphthalate, dimethylnitrosamine and methapyrilene (MPy) showed that the differences in the keyword fingerprints of these three compounds are based upon known distinct modes of action. Visualization of MPy-linked keywords and MPy-induced genes in a literature network enabled us to construct a mode of toxicity proposal for MPy, which is in agreement with known effects of MPy in literature. Compound keyword fingerprinting based on information retrieved from literature is a powerful approach for compound profiling, allowing evaluation of compound toxicity and analysis of the mode of action.

In vitro perturbations of targets in cancer hallmark processes predict rodent chemical carcinogenesis.

PubMed

Kleinstreuer, Nicole C; Dix, David J; Houck, Keith A; Kavlock, Robert J; Knudsen, Thomas B; Martin, Matthew T; Paul, Katie B; Reif, David M; Crofton, Kevin M; Hamilton, Kerry; Hunter, Ronald; Shah, Imran; Judson, Richard S

2013-01-01

Thousands of untested chemicals in the environment require efficient characterization of carcinogenic potential in humans. A proposed solution is rapid testing of chemicals using in vitro high-throughput screening (HTS) assays for targets in pathways linked to disease processes to build models for priority setting and further testing. We describe a model for predicting rodent carcinogenicity based on HTS data from 292 chemicals tested in 672 assays mapping to 455 genes. All data come from the EPA ToxCast project. The model was trained on a subset of 232 chemicals with in vivo rodent carcinogenicity data in the Toxicity Reference Database (ToxRefDB). Individual HTS assays strongly associated with rodent cancers in ToxRefDB were linked to genes, pathways, and hallmark processes documented to be involved in tumor biology and cancer progression. Rodent liver cancer endpoints were linked to well-documented pathways such as peroxisome proliferator-activated receptor signaling and TP53 and novel targets such as PDE5A and PLAUR. Cancer hallmark genes associated with rodent thyroid tumors were found to be linked to human thyroid tumors and autoimmune thyroid disease. A model was developed in which these genes/pathways function as hypothetical enhancers or promoters of rat thyroid tumors, acting secondary to the key initiating event of thyroid hormone disruption. A simple scoring function was generated to identify chemicals with significant in vitro evidence that was predictive of in vivo carcinogenicity in different rat tissues and organs. This scoring function was applied to an external test set of 33 compounds with carcinogenicity classifications from the EPA's Office of Pesticide Programs and successfully (p = 0.024) differentiated between chemicals classified as "possible"/"probable"/"likely" carcinogens and those designated as "not likely" or with "evidence of noncarcinogenicity." This model represents a chemical carcinogenicity prioritization tool supporting targeted testing and functional validation of cancer pathways.

Hepatoprotective activity of bacoside A against N-nitrosodiethylamine-induced liver toxicity in adult rats.

PubMed

Janani, Panneerselvam; Sivakumari, Kanakarajan; Parthasarathy, Chandrakesan

2009-10-01

N-Nitrosodiethylamine (DEN) is a notorious carcinogen, present in many environmental factors. DEN induces oxidative stress and cellular injury due to enhanced generation of reactive oxygen species; free radical scavengers protect the membranes from DEN-induced damage. The present study was designed to evaluate the protective effect of bacoside A (the active principle isolated from Bacopa monniera Linn.) on carcinogen-induced damage in rat liver. Adult male albino rats were pretreated with 15 mg/kg body weight/day of bacoside A orally (for 14 days) and then intoxicated with single necrogenic dose of N-nitrosodiethylamine (200 mg/kg bodyweight, intraperitonially) and maintained for 7 days. The liver weight, lipid peroxidation (LPO), and activity of serum marker enzymes (aspartate transaminases, alanine transaminases, lactate dehydrogenase, alkaline phosphatase, and gamma-glutamyl transpeptidase) were markedly increased in carcinogen-administered rats, whereas the activities of marker enzymes were near normal in bacoside A-pretreated rats. Activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutatione-S-transferase, and reduced glutathione) in liver also decreased in carcinogen-administered rats, which were significantly elevated in bacoside A-pretreated rats. It is concluded that pretreatment of bacoside A prevents the elevation of LPO and activity of serum marker enzymes and maintains the antioxidant system and thus protects the rats from DEN-induced hepatotoxicity.

Dose-related cell proliferation in medaka (Oryzias latipes) after N-nitrosodiethylamine exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ortego, L.S.; Hawkins, W.E.; Walker, W.W.

1994-12-31

Cell proliferation is important in toxic and carcinogenic mechanisms. Carcinogens such as N-nitrosodiethylamine (DEN) that cause necrotizing injury stimulate cell proliferation as part of an injury-repair mechanism. A stimulus to cell division in an organ with a low rate of cell division, such as the liver, may initiate or enhance the carcinogenicity of a chemical. The authors examined the effect of DEN exposure on cell proliferation in the liver of medaka (Oryzias latipes). Two age groups (6 and 56 days post-hatch) were exposed to DEN continuously at 5 doses (0.0, 2.5, 5.0, 10.0, and 20.0 ppm) for 28 days. Cellmore » proliferation was measured using the proliferating cell nuclear antigen (PCNA) assay two months post-initiation of DEN exposure. The assay involves monoclonal antibody detection of PCNA, an auxiliary protein of DNA polymerase delta which is, expressed during cell division. Results suggested that cell proliferation paralleled the DEN dose and that age at initiation of exposure did not affect this relationship. The increase in cell proliferation appeared to be a sustained response from that initiated during DEN exposure. The study suggests that cell proliferation in medaka is an important component in carcinogenesis and is related to carcinogen exposure dose.« less

A review of experimental evidence for the carcinogenicity of man-made vitreous fibers.

PubMed

Davis, J M

1986-01-01

This paper reviews experimental studies on the carcinogenicity of man-made vitreous fibers. Long-term inhalation studies using several animal species and dust preparations of fibrous glass, rock wool or slag wool have produced little evidence of pulmonary fibrosis or pulmonary tumors. While some intratracheal injection studies found almost no pathological changes in lung tissue, some showed that pulmonary fibrosis can occur. Only one intratracheal injection study has reported that vitreous fibers can be carcinogenic; in contrast, many workers have reported that, following intrapleural or intraperitoneal injection, man-made vitreous fibers are highly carcinogenic, and tumor production appears to be closely related to fiber size. In vitro tests confirm that vitreous fibers can be toxic and can cause neoplastic transformation of cultured cells. The discrepancies between some experimental studies probably result from the relatively high solubility of most vitreous fibers. It seems likely that, while these fibers can survive in body cavities long enough to cause tumor production, they dissolve in lung tissue fast enough to have relatively little harmful effect. Rock-wool fibers appear more durable than glass- or slag-wool fibers, and, with similar fiber numbers and sizes in any dust cloud, this material is the most likely to have harmful potential.

An Aspergillus flavus secondary metabolic gene cluster containing a hybrid PKS-NRPS is necessary for synthesis of the 2-pyridones, leporins

USDA-ARS?s Scientific Manuscript database

The genome of the filamentous fungus, Aspergillus flavus, has been shown to harbor as many as 55 putative secondary metabolic gene clusters including the one responsible for production of the toxic and carcinogenic, polyketide synthase (PKS)-derived family of secondary metabolites termed aflatoxins....

A simple approach to estimate daily loads of total, refractory, and labile organic carbon from their seasonal loads in a watershed

Treesearch

Ying Ouyang; Johnny M. Grace; Wayne C. Zipperer; Jeff Hatten; Janet Dewey

2018-01-01

Loads of naturally occurring total organic carbons (TOC), refractory organic carbon (ROC), and labile organic carbon (LOC) instreams control the availability of nutrients and the solubility and toxicity of contaminants and affect biological activities throughabsorption of light and complex metals with production of carcinogenic compounds....

Control of Aspergillus flavus growth and aflatoxin production in transgenic maize kernels expressing a tachyplesin-derived synthetic peptide, AGM182

USDA-ARS?s Scientific Manuscript database

Aspergillus flavus (A. flavus) is an opportunistic, saprophytic fungus that infects maize and other fatty acid-rich food and feed crops and produces toxic and carcinogenic secondary metabolites known as aflatoxins. Contamination of maize with aflatoxin poses a serious threat to human health in addit...

In vivo metabolism of fumonisin B1 to N-acylated ceramide-like compounds

USDA-ARS?s Scientific Manuscript database

Fumonisins are toxic and carcinogenic mycotoxins found in corn-based foods. Fumonisin B1 (FB1) metabolism to ceramide-like cytotoxic N-acylated FB1 (NAFB1) compounds has been shown in vitro, but in vivo metabolism has not been reported. Therefore, male Sprague-Dawley rats (2/group) were given 5 da...

CHARACTERIZING THE EFFECT OF CHLORINE AND CHLORAMINES ON THE FORMATION OF BIOFILM IN A SIMULATED DRINKING WATER DISTRIBUTION SYSTEM

EPA Science Inventory

Drinking wate treatment in the US has played a major role in protecting public health through the reduction of wateborne disease. However, carcinogenic and toxic contaminants continue to threaten the quality of surface and ground water in the US. The passage of the Safe Drinking ...

Degradation kinetics of aflatoxin B1 and B2 in filter paper and rough rice by using pulsed light irradiation

USDA-ARS?s Scientific Manuscript database

Rough rice is susceptible to contamination by aflatoxins, which are highly toxic, mutagenic and carcinogenic compounds. To develop aflatoxin degradation technology for rice with the use of pulsed light (PL) treatment, the objective of this study was to investigate the degradation characters of aflat...

Development of an Aquatic Bioassay for Carcinogenicity and Toxicity Testing Using the Medaka (Oryzias latipes) as a Model

DTIC Science & Technology

1990-08-15

carcinoma . In: Hepatocellular Carcinoma . K. Okuda, R Peters, eds. John Wiley and Sons, NY, pp. 3-22, 1976. 2. Harshbarger JC: Testimony for the U.S. House of...will increase the predictive ability of the aquatic bioassay. 22 V. References 1. Farber E: On the pathogenesis of experimental hepatocellular

The pathogenesis-related maize seed (PRms) gene plays a role in resistance to Aspergillus flavus infection and aflatoxin contamination

USDA-ARS?s Scientific Manuscript database

Aspergillus flavus is an opportunistic plant pathogen that colonizes and produces the toxic and carcinogenic secondary metabolites, aflatoxins, in oil-rich crops such as maize (Zea mays ssp. mays L.). Pathogenesis-related proteins serve as a first line of defense against invading pathogens by confer...

Cyclopiazonic acid is a pathogenicity factor for Aspergillus flavus and a promising target for screening germplasm for ear rot resistance

USDA-ARS?s Scientific Manuscript database

Aspergillus flavus, an opportunistic pathogen, contaminates maize and other key crops with carcinogenic aflatoxins (AF). Besides AF, A. flavus makes many more secondary metabolites (SMs), whose toxicity in insects or vertebrates has been studied. However, the role of SMs in the invasion of plant hos...

Risk Assessment for Criteria Pollutants and Air Toxics in two Sites of Mexico City During 2003 Field Campaign

NASA Astrophysics Data System (ADS)

García, A. R.; Grutter, M. M.; Volkamer, R. M.

2007-05-01

An environmental risk assessment for criteria pollutants and air toxics in Mexico City is presented. The data used in the study were collected by FTIR and DOAS systems during the Mexico City Metropolitan Area field campaign on April 2003 (MCMA2003). The systems were deployed in two different sites: One in downtown (Merced) and the other in the south east (CENICA). Concentrations of criteria pollutants and air toxics were obtained every 5 min and were used to obtain hourly average concentrations and the month average for April. The concentration values were used to estimate the risks of acute and chronic exposure to ambient concentrations using risk measures like hazard index, life cancer probability, life lost expectancy and maximum individual cancer risk. Results revealed that both sites have similar risk values. For acute exposure, criteria pollutants have larger risks than air toxics, but air toxics have larger risks for chronic exposure. Ambient concentrations of benzene showed the largest carcinogenic risk of the measured air toxics.

CHEMICAL STRUCTURE INDEXING OF TOXICITY DATA ON ...

EPA Pesticide Factsheets

Standardized chemical structure annotation of public toxicity databases and information resources is playing an increasingly important role in the 'flattening' and integration of diverse sets of biological activity data on the Internet. This review discusses public initiatives that are accelerating the pace of this transformation, with particular reference to toxicology-related chemical information. Chemical content annotators, structure locator services, large structure/data aggregator web sites, structure browsers, International Union of Pure and Applied Chemistry (IUPAC) International Chemical Identifier (InChI) codes, toxicity data models and public chemical/biological activity profiling initiatives are all playing a role in overcoming barriers to the integration of toxicity data, and are bringing researchers closer to the reality of a mineable chemical Semantic Web. An example of this integration of data is provided by the collaboration among researchers involved with the Distributed Structure-Searchable Toxicity (DSSTox) project, the Carcinogenic Potency Project, projects at the National Cancer Institute and the PubChem database. Standardizing chemical structure annotation of public toxicity databases

Safety of Traditional Arab Herbal Medicine

PubMed Central

Saad, Bashar; Azaizeh, Hassan; Abu-Hijleh, Ghassan; Said, Omar

2006-01-01

Herbal remedies are widely used for the treatment and prevention of various diseases and often contain highly active pharmacological compounds. Many medicinal herbs and pharmaceutical drugs are therapeutic at one dose and toxic at another. Toxicity related to traditional medicines is becoming more widely recognized as these remedies become popular in the Mediterranean region as well as worldwide. Most reports concerning the toxic effects of herbal medicines are associated with hepatotoxicity although reports of other toxic effects including kidney, nervous system, blood, cardiovascular and dermatologic effects, mutagenicity and carcinogenicity have also been published in the medical literature. This article presents a systematic review on safety of traditional Arab medicine and the contribution of Arab scholars to toxicology. Use of modern cell biological, biochemical, in vitro and in vivo techniques for the evaluation of medicinal plants safety is also discussed. PMID:17173106

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shen, Jun; Wanibuchi, Hideki; Waalkes, Michael P.

Epidemiological studies indicated that human arsenic exposure can induce urinary bladder cancer. Methylation of inorganic arsenic can generate more reactive and toxic organic arsenical species. In this regard, it was recently reported that the methylated arsenical metabolite, dimethylarsinic acid [DMA(V)], induced urinary bladder tumors in rats. However, other methylated metabolites, like monomethylarsonic acid [MMA(V)] and trimethylarsine oxide (TMAO) were not carcinogenic to the urinary bladder. In order to compare the early effects of DMA(V), MMA(V), and TMAO on the urinary bladder transitional cell epithelium at the scanning electron microscope (SEM) level, we investigated the sub-chronic (13 weeks) toxicological effects ofmore » MMA(V) (187 ppm), DMA(V) (184 ppm), TMAO (182 ppm) given in the drinking water to male and female F344 rats with a focus on the urinary bladder in this study. Obvious pathological changes, including ropy microridges, pitting, increased separation of epithelial cells, exfoliation, and necrosis, were found in the urinary bladders of both sexes, but particularly in females receiving carcinogenic doses of DMA(V). Urine arsenical metabolic differences were found between males and females, with levels of MMA(III), a potential genotoxic form, higher in females treated with DMA(V) than in males. Thus, this study provides clear evidence that DMA(V) is more toxic to the female urinary bladder, in accord with sensitivity to carcinogenesis. Important gender-related metabolic differences including enhanced presentation of MMA(III) to the urothelial cells might possibly account for heightened sensitivity in females. However, the potential carcinogenic effects of MMA(III) need to be further elucidated.« less

A comparison of the results from intra-pleural and intra-peritoneal studies with those from inhalation and intratracheal tests for the assessment of pulmonary responses to inhalable dusts and fibres.

PubMed

Drummond, Gail; Bevan, Ruth; Harrison, Paul

2016-11-01

The aim of this paper is to compare results from inhalation studies with those from intraperitoneal and intrapleural tests, where available, for a number of fibrous and particulate test materials. The objective is to determine how well intraperitoneal/intrapleural studies predict the pathological responses observed in more standard in vivo studies of pulmonary toxicity, with a particular focus on carcinogenicity. Published toxicity data was obtained for a number of materials including asbestos, wollastonite, MMVFs (including glass fibres, stone wools and RCF), silicon carbide whiskers, potassium octatitanate, quartz, kevlar, polypropylene and titanium dioxide. For some of the fibrous material reviewed, there is conformity between the results of intraperitoneal and inhalation tests such that they are either consistently positive or consistently negative. For the remaining fibrous materials reviewed, intraperitoneal and inhalation tests give different results, with positive results in the intraperitoneal test not being reflected by positive inhalation results. It is suggested that the intraperitoneal test can be used to exonerate a dust or fibre (because if negative in the intraperitoneal test it is extremely unlikely to be positive in either inhalation or intratracheal tests) but should not be used to positively determine that a dust or fibre is carcinogenic by inhalation. We would argue against the use of intraperitoneal tests for human health risk assessment except perhaps for the purpose of exoneration of a material from classification as a carcinogen. Copyright © 2016 Elsevier Inc. All rights reserved.

Small difference in carcinogenic potency between GBP nanomaterials and GBP micromaterials.

PubMed

Gebel, Thomas

2012-07-01

Materials that can be described as respirable granular biodurable particles without known significant specific toxicity (GBP) show a common mode of toxicological action that is characterized by inflammation and carcinogenicity in chronic inhalation studies in the rat. This study was carried out to compare the carcinogenic potency of GBP nanomaterials (primary particle diameter 1-100 nm) to GBP micromaterials (primary particle diameter >100 nm) in a pooled approach. For this purpose, the positive GBP rat inhalation carcinogenicity studies have been evaluated. Inhalation studies on diesel engine emissions have also been included due to the fact that the mode of carcinogenic action is assumed to be the same. As it is currently not clear which dose metrics may best explain carcinogenic potency, different metrics have been considered. Cumulative exposure concentrations related to mass, surface area, and primary particle volume have been included as well as cumulative lung burden metrics related to mass, surface area, and primary particle volume. In total, 36 comparisons have been conducted. Including all dose metrics, GBP nanomaterials were 1.33- to 1.69-fold (mean values) and 1.88- to 3.54-fold (median values) more potent with respect to carcinogenicity than GBP micromaterials, respectively. Nine of these 36 comparisons showed statistical significance (p < 0.05, U test), all of which related to dose metrics based on particle mass. The maximum comparative potency factor obtained for one of these 9 dose metric comparisons based on particle mass was 4.71. The studies with diesel engine emissions did not have a major impact on the potency comparison. The average duration of the carcinogenicity studies with GBP nanomaterials was 4 months longer (median values 30 vs. 26 months) than the studies with GBP micromaterials, respectively. Tumor rates increase with age and lung tumors in the rat induced by GBP materials are known to appear late, that is, mainly after study durations longer than 24 months. Taking the different study durations into account, the real potency differences were estimated to be twofold lower than the relative potency factors identified. In conclusion, the chronic rat inhalation studies with GBP materials indicate that the difference in carcinogenic potency between GBP nanomaterials and GBP micromaterials is low can be described by a factor of 2-2.5 referring to the dose metrics mass concentration.

76 FR 16285 - Amendments to the Water Quality Regulations, Water Code and Comprehensive Plan To Update Water...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-23

... Plan to update the Commission's human health and aquatic life stream quality objectives (also called... DELAWARE RIVER BASIN COMMISSION 18 CFR Part 410 Amendments to the Water Quality Regulations, Water Code and Comprehensive Plan To Update Water Quality Criteria for Toxic Pollutants in the Delaware...

Biological monitoring to determine worker dose in a butadiene processing plant

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bechtold, W.E.; Hayes, R.B.

1995-12-01

Butadiene (BD) is a reactive gas used extensively in the rubber industry and is also found in combustion products. Although BD is genotoxic and acts as an animal carcinogen, the evidence for carcinogenicity in humans is limited. Extrapolation from animal studies on BD carcinogenicity to risk in humans has been controversial because of uncertainties regarding relative biologic exposure and related effects in humans vs. experimental animals. To reduce this uncertainty, a study was designed to characterize exposure to BD at a polymer production facility and to relate this exposure to mutational and cytogenetic effects. Biological monitoring was used to bettermore » assess the internal dose of BD received by the workers. Measurement of 1,2-dihydroxy-4-(N-acetylcysteinyl) butane (M1) in urine served as the biomarker in this study. M1 has been shown to correlate with area monitoring in previous studies. Most studies that relate exposure to a toxic chemical with its biological effects rely on exposure concentration as the dose metric; however, exposure concentration may or may not reflect the actual internal dose of the chemical.« less

High- to low-dose extrapolation: critical determinants involved in the dose response of carcinogenic substances.

PubMed

Swenberg, J A; Richardson, F C; Boucheron, J A; Deal, F H; Belinsky, S A; Charbonneau, M; Short, B G

1987-12-01

Recent investigations on mechanism of carcinogenesis have demonstrated important quantitative relationships between the induction of neoplasia, the molecular dose of promutagenic DNA adducts and their efficiency for causing base-pair mismatch, and the extent of cell proliferation in target organ. These factors are involved in the multistage process of carcinogenesis, including initiation, promotion, and progression. The molecular dose of DNA adducts can exhibit supralinear, linear, or sublinear relationships to external dose due to differences in absorption, biotransformation, and DNA repair at high versus low doses. In contrast, increased cell proliferation is a common phenomena that is associated with exposures to relatively high doses of toxic chemicals. As such, it enhances the carcinogenic response at high doses, but has little effect at low doses. Since data on cell proliferation can be obtained for any exposure scenario and molecular dosimetry studies are beginning to emerge on selected chemical carcinogens, methods are needed so that these critical factors can be utilized in extrapolation from high to low doses and across species. The use of such information may provide a scientific basis for quantitative risk assessment.

High- to low-dose extrapolation: critical determinants involved in the dose response of carcinogenic substances.

PubMed Central

Swenberg, J A; Richardson, F C; Boucheron, J A; Deal, F H; Belinsky, S A; Charbonneau, M; Short, B G

1987-01-01

Recent investigations on mechanism of carcinogenesis have demonstrated important quantitative relationships between the induction of neoplasia, the molecular dose of promutagenic DNA adducts and their efficiency for causing base-pair mismatch, and the extent of cell proliferation in target organ. These factors are involved in the multistage process of carcinogenesis, including initiation, promotion, and progression. The molecular dose of DNA adducts can exhibit supralinear, linear, or sublinear relationships to external dose due to differences in absorption, biotransformation, and DNA repair at high versus low doses. In contrast, increased cell proliferation is a common phenomena that is associated with exposures to relatively high doses of toxic chemicals. As such, it enhances the carcinogenic response at high doses, but has little effect at low doses. Since data on cell proliferation can be obtained for any exposure scenario and molecular dosimetry studies are beginning to emerge on selected chemical carcinogens, methods are needed so that these critical factors can be utilized in extrapolation from high to low doses and across species. The use of such information may provide a scientific basis for quantitative risk assessment. PMID:3447904

75 FR 17333 - Addition of National Toxicology Program Carcinogens; Community Right-to-Know Toxic Chemical...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-06

... encryption, and be free of any defects or viruses. Docket: All documents in the docket are listed in the www... Community Right-to-Know Hotline, toll free at (800) 424-9346 or (703) 412-9810 in Virginia and Alaska or toll free, TDD (800) 553-7672, http://www.epa.gov/epaoswer/hotline/ . SUPPLEMENTARY INFORMATION: I...

CHARACTERIZATION OF STABLE BENZO(A)PYRENE-7,8-QUINONE-DNA ADDUCTS IN CALF THYMUS DNA

EPA Science Inventory

Benzo[alpyrene-7,8-dione (BPQ) is a reactive aldo-keto reductase-mediated product of B[a]P-7,8-diol, a major P450/epoxide hydrolase metabolite of the multi-species carcinogen, B[a]P. The role of BPQ in B[a]P's genotoxicity and carcinogenesis is evolving. Toxicity pathways involvi...

Equivalency testing of ultraviolet disinfection for wastewater reclamation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oppenheimer, J.A.; Jacangelo, J.G.; Laine, J.M.

1996-11-01

UV light disinfection was shown to continuously provide microbial inactivation equivalent to chlorine while reducing the formation of known carcinogenic disinfection by-products and the formation of chronic whole effluent toxicity. This was the first study to demonstrate UV`s performance relative to chlorination over an extended timeframe at a full-scale facility treating to meet the most stringent California reclamation standards.

The Aspergillus flavus spermidine synthase (spds) gene, is required for normal development, aflatoxin production, and pathogenesis during infection of maize kernels

USDA-ARS?s Scientific Manuscript database

Aspergillus flavus is a soil-borne saprophyte and an opportunistic pathogen of both humans and plants. This fungus not only causes disease in several important food and feed crops such as maize, peanut, cottonseed and tree nuts but also produces the toxic and carcinogenic secondary metabolites (SMs)...

Enhancement of cadmium ion sorption capacity of lignocellulosic bio-sorbent by sulfonation

Treesearch

Eun W. Shin; James S. Han; Roger M. Rowell; Soo-Hong Min; James O. Peterson

2003-01-01

Water contaminated by heavy metals remains a serious environmental and public health problem. Cadmium is a toxic heavy metal that not only causes choking, abdominal pain, anemia, renal dysfunction, and diarrhea, but also has been listed as a carcinogen by the EPA (Gaballah and Kibertus, 1998). Among current technologies used to reduce the amount of heavy metals in...

Coal-tar-based pavement sealcoat, polycyclic aromatic Hydrocarbons (PAHs), and environmental health

USGS Publications Warehouse

Mahler, B.J.; Van Metre, P.C.

2011-01-01

Studies by the U.S. Geological Survey (USGS) have identified coal-tar-based sealcoat-the black, viscous liquid sprayed or painted on asphalt pavement such as parking lots-as a major source of polycyclic aromatic hydrocarbon (PAH) contamination in urban areas for large parts of the Nation. Several PAHs are suspected human carcinogens and are toxic to aquatic life.

Aflatoxin-producing fungi in maize field soils from sea level to over 2000 masl: A three year study in Sonora, Mexico

USDA-ARS?s Scientific Manuscript database

Aflatoxins, highly toxic carcinogens produced by several members of Aspergillus section Flavi, contaminate crops in temperate zones. Maize is cultivated from 0 to 2,100 masl under diverse growing regimes in the state of Sonora, Mexico. This is typical of the nation. In order to design sampling strat...

Dietary inorganic nitrate: From villain to hero in metabolic disease?

PubMed Central

McNally, Ben; Griffin, Julian L.

2015-01-01

Historically, inorganic nitrate was believed to be an inert by‐product of nitric oxide (NO) metabolism that was readily excreted by the body. Studies utilising doses of nitrate far in excess of dietary and physiological sources reported potentially toxic and carcinogenic effects of the anion. However, nitrate is a significant component of our diets, with the majority of the anion coming from green leafy vegetables, which have been consistently shown to offer protection against obesity, type 2 diabetes and metabolic diseases. The discovery of a metabolic pathway in mammals, in which nitrate is reduced to NO, via nitrite, has warranted a re‐examination of the physiological role of this small molecule. Obesity, type 2 diabetes and the metabolic syndrome are associated with a decrease in NO bioavailability. Recent research suggests that the nitrate‐nitrite‐NO pathway may be harnessed as a therapeutic to supplement circulating NO concentrations, with both anti‐obesity and anti‐diabetic effects, as well as improving vascular function. In this review, we examine the key studies that have led to the re‐evaluation of the physiological function of inorganic nitrate, from toxic and carcinogenic metabolite, to a potentially important and beneficial agent in the treatment of metabolic disease. PMID:26227946

The carcinogenic potencies of 2,3,7,8-tetrachlorodibenzo-p-dioxin: Letting the data speak for themselves

DOE Office of Scientific and Technical Information (OSTI.GOV)

Green, L.C.; Crouch, E.A.C.; Lester, R.R.

1996-12-31

The authors analyze here the dose-response data generated from the seminal bioassay of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) in Sprague-Dawley rats, reported by Kociba and coworkers. That chronic toxicity and oncogenicity study showed 2,3,7,8-TCDD to increase the incidence of certain tumors, while decreasing the incidence of others. Further, results in female rats were markedly different from those in male rats--a result ascribed to the dependence of dioxin on estrogen for some of its toxic effects. For each sex, the authors analyze each tumor type on which 2,3,7,8-TCDD has, or might have, an effect, whether positive, negative, or neutral. After generating dose-response relationships formore » each tumor type, the authors combine them. The combination involves simply adding the slopes of each tumor-specific dose-response relationship. They perform separate analyses for each set of dose-ranges. They also calculate upper (and lower) bounds on the maximum likelihood estimates, using the upper 95th percentile estimates for the slopes of the net dose-response relationships as conservative estimates of carcinogenic potency.« less

The EPA Children’s Environmental Health Yearbook Supplement (2000)

EPA Pesticide Factsheets

New projects and updates to some ongoing projects already described in the 1998 Yearbook, including sections on asthma, childhood cancer, developmental/neurological toxicity, pesticides, contaminated water, and updated list of Children's Health Resources.

DISTRIBUTED STRUCTURE-SEARCHABLE TOXICITY ...

EPA Pesticide Factsheets

The ability to assess the potential genotoxicity, carcinogenicity, or other toxicity of pharmaceutical or industrial chemicals based on chemical structure information is a highly coveted and shared goal of varied academic, commercial, and government regulatory groups. These diverse interests often employ different approaches and have different criteria and use for toxicity assessments, but they share a need for unrestricted access to existing public toxicity data linked with chemical structure information. Currently, there exists no central repository of toxicity information, commercial or public, that adequately meets the data requirements for flexible analogue searching, SAR model development, or building of chemical relational databases (CRD). The Distributed Structure-Searchable Toxicity (DSSTox) Public Database Network is being proposed as a community-supported, web-based effort to address these shared needs of the SAR and toxicology communities. The DSSTox project has the following major elements: 1) to adopt and encourage the use of a common standard file format (SDF) for public toxicity databases that includes chemical structure, text and property information, and that can easily be imported into available CRD applications; 2) to implement a distributed source approach, managed by a DSSTox Central Website, that will enable decentralized, free public access to structure-toxicity data files, and that will effectively link knowledgeable toxicity data s

Bioavailability, Intracellular Mobilization of Nickel, and HIF-1α Activation in Human Lung Epithelial Cells Exposed to Metallic Nickel and Nickel Oxide Nanoparticles

PubMed Central

Liu, Xinyuan; Smith, Ashley; McNeil, Kevin; Weston, Paula; Zhitkovich, Anatoly; Hurt, Robert; Kane, Agnes B.

2011-01-01

Micron-sized particles of poorly soluble nickel compounds, but not metallic nickel, are established human and rodent carcinogens. In contrast, little is known about the toxic effects of a growing number of Ni-containing materials in the nano-sized range. Here, we performed physicochemical characterization of NiO and metallic Ni nanoparticles and examined their metal ion bioavailability and toxicological properties in human lung epithelial cells. Cellular uptake of metallic Ni and NiO nanoparticles, but not metallic Ni microparticles, was associated with the release of Ni(II) ions after 24–48 h as determined by Newport Green fluorescence. Similar to soluble NiCl2, NiO nanoparticles induced stabilization and nuclear translocation of hypoxia-inducible factor 1α (HIF-1α) transcription factor followed by upregulation of its target NRDG1 (Cap43). In contrast to no response to metallic Ni microparticles, nickel nanoparticles caused a rapid and prolonged activation of the HIF-1α pathway that was stronger than that induced by soluble Ni (II). Soluble NiCl2 and NiO nanoparticles were equally toxic to H460 human lung epithelial cells and primary human bronchial epithelial cells; metallic Ni nanoparticles showed lower toxicity and Ni microparticles were nontoxic. Cytotoxicity induced by all forms of Ni occurred concomitant with activation of an apoptotic response, as determined by dose- and time-dependent cleavage of caspases and poly (ADP-ribose) polymerase. Our results show that metallic Ni nanoparticles, in contrast to micron-sized Ni particles, activate a toxicity pathway characteristic of carcinogenic Ni compounds. Moderate cytotoxicity and sustained activation of the HIF-1α pathway by metallic Ni nanoparticles could promote cell transformation and tumor progression. PMID:21828359

Alternative (non-animal) methods for cosmetics testing: current status and future prospects-2010.

PubMed

Adler, Sarah; Basketter, David; Creton, Stuart; Pelkonen, Olavi; van Benthem, Jan; Zuang, Valérie; Andersen, Klaus Ejner; Angers-Loustau, Alexandre; Aptula, Aynur; Bal-Price, Anna; Benfenati, Emilio; Bernauer, Ulrike; Bessems, Jos; Bois, Frederic Y; Boobis, Alan; Brandon, Esther; Bremer, Susanne; Broschard, Thomas; Casati, Silvia; Coecke, Sandra; Corvi, Raffaella; Cronin, Mark; Daston, George; Dekant, Wolfgang; Felter, Susan; Grignard, Elise; Gundert-Remy, Ursula; Heinonen, Tuula; Kimber, Ian; Kleinjans, Jos; Komulainen, Hannu; Kreiling, Reinhard; Kreysa, Joachim; Leite, Sofia Batista; Loizou, George; Maxwell, Gavin; Mazzatorta, Paolo; Munn, Sharon; Pfuhler, Stefan; Phrakonkham, Pascal; Piersma, Aldert; Poth, Albrecht; Prieto, Pilar; Repetto, Guillermo; Rogiers, Vera; Schoeters, Greet; Schwarz, Michael; Serafimova, Rositsa; Tähti, Hanna; Testai, Emanuela; van Delft, Joost; van Loveren, Henk; Vinken, Mathieu; Worth, Andrew; Zaldivar, José-Manuel

2011-05-01

The 7th amendment to the EU Cosmetics Directive prohibits to put animal-tested cosmetics on the market in Europe after 2013. In that context, the European Commission invited stakeholder bodies (industry, non-governmental organisations, EU Member States, and the Commission's Scientific Committee on Consumer Safety) to identify scientific experts in five toxicological areas, i.e. toxicokinetics, repeated dose toxicity, carcinogenicity, skin sensitisation, and reproductive toxicity for which the Directive foresees that the 2013 deadline could be further extended in case alternative and validated methods would not be available in time. The selected experts were asked to analyse the status and prospects of alternative methods and to provide a scientifically sound estimate of the time necessary to achieve full replacement of animal testing. In summary, the experts confirmed that it will take at least another 7-9 years for the replacement of the current in vivo animal tests used for the safety assessment of cosmetic ingredients for skin sensitisation. However, the experts were also of the opinion that alternative methods may be able to give hazard information, i.e. to differentiate between sensitisers and non-sensitisers, ahead of 2017. This would, however, not provide the complete picture of what is a safe exposure because the relative potency of a sensitiser would not be known. For toxicokinetics, the timeframe was 5-7 years to develop the models still lacking to predict lung absorption and renal/biliary excretion, and even longer to integrate the methods to fully replace the animal toxicokinetic models. For the systemic toxicological endpoints of repeated dose toxicity, carcinogenicity and reproductive toxicity, the time horizon for full replacement could not be estimated.

Is senna laxative use associated to cathartic colon, genotoxicity, or carcinogenicity?

PubMed

Morales, M A; Hernández, D; Bustamante, S; Bachiller, I; Rojas, A

2009-01-01

Due to their natural origin, apparent low oral toxicity, effectiveness, and accessibility without a medical prescription, the anthranoid laxatives are a popular remedy for constipation and are frequently used abusively. Therefore, it is important to characterize its harmful and/or toxic effects. The sennosides, main active metabolites of senna, exhibit a very low toxicity in rats, and its genotoxic activity in bacterial strains as well as mammal cells was classified as weak in those cases where it was shown to be significant. The toxicological and mutagenic status of the crude extract of senna, however, is not as well characterized, and it is necessary to do so since it is frequently, and at the same time incorrectly, believed that the chronic use of anthranoid laxatives is a risk factor for the development of colorectal cancer. The objective of this article was to review the information that arises in various scientific medical databases using key words such as senna, sen, Senna alexandrina, Cassia angustifolia, sennosides, laxative toxicity, mainly ISI and non-ISI articles of journals with an editorial committee. Web pages of products or companies that publicize or commercialize this type of laxative were not included. This analysis establishes that (1) there is no convincing evidence that the chronic use of senna has, as a consequence, a structural and/or functional alteration of the enteric nerves or the smooth intestinal muscle, (2) there is no relation between long-term administration of a senna extract and the appearance of gastrointestinal tumors or any other type in rats, (3) senna is not carcinogenic in rats even after a two-year daily dose of up to 300 mg/kg/day, and (4) the current evidence does not show that there is a genotoxic risk for patients who take laxatives containing senna extracts or sennosides.

Modeling of Toxicity-Relevant Electrophilic Reactivity for Guanine with Epoxides: Estimating the Hard and Soft Acids and Bases (HSAB) Parameter as a Predictor.

PubMed

Zhang, Jing; Wang, Chenchen; Ji, Li; Liu, Weiping

2016-05-16

According to the electrophilic theory in toxicology, many chemical carcinogens in the environment and/or their active metabolites are electrophiles that exert their effects by forming covalent bonds with nucleophilic DNA centers. The theory of hard and soft acids and bases (HSAB), which states that a toxic electrophile reacts preferentially with a biological macromolecule that has a similar hardness or softness, clarifies the underlying chemistry involved in this critical event. Epoxides are hard electrophiles that are produced endogenously by the enzymatic oxidation of parent chemicals (e.g., alkenes and PAHs). Epoxide ring opening proceeds through a SN2-type mechanism with hard nucleophile DNA sites as the major facilitators of toxic effects. Thus, the quantitative prediction of chemical reactivity would enable a predictive assessment of the molecular potential to exert electrophile-mediated toxicity. In this study, we calculated the activation energies for reactions between epoxides and the guanine N7 site for a diverse set of epoxides, including aliphatic epoxides, substituted styrene oxides, and PAH epoxides, using a state-of-the-art density functional theory (DFT) method. It is worth noting that these activation energies for diverse epoxides can be further predicted by quantum chemically calculated nucleophilic indices from HSAB theory, which is a less computationally demanding method than the exacting procedure for locating the transition state. More importantly, the good qualitative/quantitative correlations between the chemical reactivity of epoxides and their bioactivity suggest that the developed model based on HSAB theory may aid in the predictive hazard evaluation of epoxides, enabling the early identification of mutagenicity/carcinogenicity-relevant SN2 reactivity.

Risk assessment of bioaccessible trace elements in smoke haze aerosols versus urban aerosols using simulated lung fluids

NASA Astrophysics Data System (ADS)

Huang, Xian; Betha, Raghu; Tan, Li Yun; Balasubramanian, Rajasekhar

2016-01-01

Smoke-haze episodes, caused by uncontrolled peat and forest fires, occur almost every year in the South-East Asian region with increased concentrations of PM2.5 (airborne particulate matter (PM) with diameter ≤ 2.5 μm). Particulate-bound trace elements (TrElems), especially carcinogenic and toxic elements, were measured during smoke haze as well as non-haze periods in 2014 as they are considered to be indicators of potential health effects. The bioaccessibilities of 13 TrElems were investigated using two types of simulated lung fluids (SLFs), Gamble's solution and artificial lysosomal fluid (ALF), instead of the commonly used leaching agent (water). The dissolution kinetics was also examined for these TrElems. Many TrElems showed higher solubility in SLFs, and were more soluble in ALF compared to the Gamble's solution. Cu, Mn and Cd were observed to be the most soluble trace elements in ALF, while in Gamble's solution the most soluble trace elements were Cu, Mn and Zn. The dissolution rates were highly variable among the elements. Health risk assessment was conducted based on the measured concentrations of TrElems and their corresponding toxicities for three possible scenarios involving interactions between carcinogenic and toxic TrElems and SLFs, using the United States Environmental Protection Agency (USEPA) human health risk assessment model. The cumulative cancer risks exceeded the acceptable level (1 in a million i.e. 1 × 10-6). However, the estimation of health quotient (HQ) indicated no significant chronic toxic health effects. The risk assessment results revealed that the assessment of bioaccessibility of particulate-bound TrElems using water as the leaching agent may underestimate the health risk.

Hepatic transcriptomic alterations for N,N-dimethyl-p-toluidine (DMPT) and p-toluidine after 5-day exposure in rats.

PubMed

Dunnick, June K; Shockley, Keith R; Morgan, Daniel L; Brix, Amy; Travlos, Gregory S; Gerrish, Kevin; Michael Sanders, J; Ton, T V; Pandiri, Arun R

2017-04-01

N,N-dimethyl-p-toluidine (DMPT), an accelerant for methyl methacrylate monomers in medical devices, was a liver carcinogen in male and female F344/N rats and B6C3F1 mice in a 2-year oral exposure study. p-Toluidine, a structurally related chemical, was a liver carcinogen in mice but not in rats in an 18-month feed exposure study. In this current study, liver transcriptomic data were used to characterize mechanisms in DMPT and p-toluidine liver toxicity and for conducting benchmark dose (BMD) analysis. Male F344/N rats were exposed orally to DMPT or p-toluidine (0, 1, 6, 20, 60 or 120 mg/kg/day) for 5 days. The liver was examined for lesions and transcriptomic alterations. Both chemicals caused mild hepatic toxicity at 60 and 120 mg/kg and dose-related transcriptomic alterations in the liver. There were 511 liver transcripts differentially expressed for DMPT and 354 for p-toluidine at 120 mg/kg/day (false discovery rate threshold of 5 %). The liver transcriptomic alterations were characteristic of an anti-oxidative damage response (activation of the Nrf2 pathway) and hepatic toxicity. The top cellular processes in gene ontology (GO) categories altered in livers exposed to DMPT or p-toluidine were used for BMD calculations. The lower confidence bound benchmark doses for these chemicals were 2 mg/kg/day for DMPT and 7 mg/kg/day for p-toluidine. These studies show the promise of using 5-day target organ transcriptomic data to identify chemical-induced molecular changes that can serve as markers for preliminary toxicity risk assessment.

A 13-week repeated dose study of three 3-monochloropropane-1,2-diol fatty acid esters in F344 rats.

PubMed

Onami, Saeko; Cho, Young-Man; Toyoda, Takeshi; Mizuta, Yasuko; Yoshida, Midori; Nishikawa, Akiyoshi; Ogawa, Kumiko

2014-04-01

3-monochloropropane-1,2-diol (3-MCPD), a rat renal and testicular carcinogen, has been reported to occur in various foods and food ingredients as free or esterified forms. Since reports about toxicity of 3-MCPD esters are limited, we conducted a 13-week rat subchronic toxicity study of 3-MCPD esters (palmitate diester: CDP, palmitate monoester: CMP, oleate diester: CDO). We administered a carcinogenic dose (3.6 × 10(-4) mol/kg B.W./day) of 3-MCPD or these esters at equimolar concentrations and two 1/4 lower doses by gavage with olive oil as a vehicle five times a week for 13 weeks to F344 male and female rats. As a result, five out of ten 3-MCPD-treated females died from acute renal tubular necrosis, but none of the ester-treated rats. Decreased HGB was observed in all high-dose 3-MCPD fatty acid ester-treated rats, except CDO-treated males. The absolute and relative kidney weights were significantly increased in the ester-treated rats at medium and high doses. Relative liver weights were significantly increased in the esters-treated rat at high dose, except for CMP females. Significant increase in apoptotic epithelial cells in the initial segment of the epididymis of high-dose ester-treated males was also observed. The results suggested that although acute renal toxicity was lower than 3-MCPD, these three 3-MCPD fatty acid esters have the potential to exert subchronic toxicity to the rat kidneys and epididymis, to a similar degree as 3-MCPD under the present conditions. NOAELs (no-observed-adverse-effect levels) of CDP, CMP and CDO were suggested to be 14, 8 and 15 mg/kg B.W./day, respectively.

Risk assessment on mixture toxicity of arsenic, zinc and copper intake from consumption of milkfish, Chanos chanos (Forsskål), cultured using contaminated groundwater in Southwest Taiwan.

PubMed

Lin, Ming-Chao

2009-07-01

Studies on bioaccumulation of arsenic, zinc, and copper in freshwater-cultured milkfish were carried out to assess the risks on human health. The arsenic, zinc, and copper levels in milkfish showed significant positive correlations to the arsenic, zinc, and copper concentrations in pond water. The hazard index of arsenic, zinc, and copper mixture for intake of milkfish (1.75 +/- 0.65) demonstrated that intake of in this way contaminated milkfish will result in non-carcinogenic risk. The target cancer risk of arsenic for intake of the milkfish (2.74 x 10(-4) +/- 1.18 x 10(-4)) indicated that the inhabitants were exposed to arsenic pollution with carcinogenic risk.

Prediction of rodent carcinogenic potential of naturally occurring chemicals in the human diet using high-throughput QSAR predictive modeling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Valerio, Luis G.; Arvidson, Kirk B.; Chanderbhan, Ronald F.

2007-07-01

Consistent with the U.S. Food and Drug Administration (FDA) Critical Path Initiative, predictive toxicology software programs employing quantitative structure-activity relationship (QSAR) models are currently under evaluation for regulatory risk assessment and scientific decision support for highly sensitive endpoints such as carcinogenicity, mutagenicity and reproductive toxicity. At the FDA's Center for Food Safety and Applied Nutrition's Office of Food Additive Safety and the Center for Drug Evaluation and Research's Informatics and Computational Safety Analysis Staff (ICSAS), the use of computational SAR tools for both qualitative and quantitative risk assessment applications are being developed and evaluated. One tool of current interest ismore » MDL-QSAR predictive discriminant analysis modeling of rodent carcinogenicity, which has been previously evaluated for pharmaceutical applications by the FDA ICSAS. The study described in this paper aims to evaluate the utility of this software to estimate the carcinogenic potential of small, organic, naturally occurring chemicals found in the human diet. In addition, a group of 19 known synthetic dietary constituents that were positive in rodent carcinogenicity studies served as a control group. In the test group of naturally occurring chemicals, 101 were found to be suitable for predictive modeling using this software's discriminant analysis modeling approach. Predictions performed on these compounds were compared to published experimental evidence of each compound's carcinogenic potential. Experimental evidence included relevant toxicological studies such as rodent cancer bioassays, rodent anti-carcinogenicity studies, genotoxic studies, and the presence of chemical structural alerts. Statistical indices of predictive performance were calculated to assess the utility of the predictive modeling method. Results revealed good predictive performance using this software's rodent carcinogenicity module of over 1200 chemicals, comprised primarily of pharmaceutical, industrial and some natural products developed under an FDA-MDL cooperative research and development agreement (CRADA). The predictive performance for this group of dietary natural products and the control group was 97% sensitivity and 80% concordance. Specificity was marginal at 53%. This study finds that the in silico QSAR analysis employing this software's rodent carcinogenicity database is capable of identifying the rodent carcinogenic potential of naturally occurring organic molecules found in the human diet with a high degree of sensitivity. It is the first study to demonstrate successful QSAR predictive modeling of naturally occurring carcinogens found in the human diet using an external validation test. Further test validation of this software and expansion of the training data set for dietary chemicals will help to support the future use of such QSAR methods for screening and prioritizing the risk of dietary chemicals when actual animal data are inadequate, equivocal, or absent.« less

Phenols, flame retardants and phthalates in water and wastewater - a global problem.

PubMed

Ayanda, Olushola Sunday; Olutona, Godwin Oladele; Olumayede, Emmanuel G; Akintayo, Cecilia O; Ximba, Bhekumusa J

Organic pollutants in water and wastewater have been causing serious environmental problems. The arbitrary discharge of wastewater by industries, and handling, use, and disposal constitute a means by which phenols, flame retardants (FRs), phthalates (PAEs) and other toxic organic pollutants enter the ecosystem. Moreover, these organic pollutants are not completely removed during treatment processes and might be degraded into highly toxic derivatives, which has led to their occurrence in the environment. Phenols, FRs and PAEs are thus highly toxic, carcinogenic and mutagenic, and are capable of disrupting the endocrine system. Therefore, investigation to understand the sources, pathways, behavior, toxicity and exposure to phenols, FRs and PAEs in the environment is necessary. Formation of different by-products makes it difficult to compare the efficacy of the treatment processes, most especially when other organic matters are present. Hence, high levels of phenols, FRs and PAEs removal could be attained with in-line combined treatment processes.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ammann, H.M.; Bradow, F.; Fennell, D.

Hydrogen sulfide is a highly toxic gas which is immediately lethal in concentrations greater than 2000 ppm. The toxic end-point is due to anoxia to brain and heart tissues which results from its interaction with the celluar enzyme cytochrome oxidase. Inhibition of the enzyme halts oxidative metabolism which is the primary energy source for cells. A second toxic end-point is the irritative effect of hydrogen sulfide on mucous membranes, particularly edema at sublethal doses (250 to 500 ppm) in which sufficient exposure occurs before conciousness is lost. Recovered victims of exposure report neurologic symptoms such as headache, fatigue, irritability, vertigo,more » and loss of libido. Long-term effects are similar to those caused by anoxia due to other toxic agents like CO, and probably are not due to specific H/sub 2/S effects. H/sub 2/S is not a cumulative poison. No mutagenic, carcinogenic, reproductive, or teratogenic effects have been reported in the literature.« less

The Third American Society of Regional Anesthesia and Pain Medicine Practice Advisory on Local Anesthetic Systemic Toxicity: Executive Summary 2017.

PubMed

Neal, Joseph M; Barrington, Michael J; Fettiplace, Michael R; Gitman, Marina; Memtsoudis, Stavros G; Mörwald, Eva E; Rubin, Daniel S; Weinberg, Guy

2018-02-01

The American Society of Regional Anesthesia and Pain Medicine's Third Practice Advisory on local anesthetic systemic toxicity is an interim update from its 2010 advisory. The advisory focuses on new information regarding the mechanisms of lipid resuscitation, updated frequency estimates, the preventative role of ultrasound guidance, changes to case presentation patterns, and limited information related to local infiltration anesthesia and liposomal bupivacaine. In addition to emerging information, the advisory updates recommendations pertaining to prevention, recognition, and treatment of local anesthetic systemic toxicity. WHAT'S NEW IN THIS UPDATE?: This interim update summarizes recent scientific findings that have enhanced our understanding of the mechanisms that lead to lipid emulsion reversal of LAST, including rapid partitioning, direct inotropy, and post-conditioning. Since the previous practice advisory, epidemiological data have emerged that suggest a lower frequency of LAST as reported by single institutions and some registries, nevertheless a considerable number of events still occur within the general community. Contemporary case reports suggest a trend toward delayed presentation, which may mirror the increased use of ultrasound guidance (fewer intravascular injections), local infiltration techniques (slower systemic uptake), and continuous local anesthetic infusions. Small patient size and sarcopenia are additional factors that increase potential risk for LAST. An increasing number of reported events occur outside of the traditional hospital setting and involve non-anesthesiologists.

Occupational health assessment of chromite toxicity among Indian miners

PubMed Central

Das, Alok Prasad; Singh, Shikha

2011-01-01

Elevated concentration of hexavalent chromium pollution and contamination has contributed a major health hazard affecting more than 2 lakh mine workers and inhabitants residing in the Sukinda chromite mine of Odisha, India. Despite people suffering from several forms of ill health, physical and mental deformities, constant exposure to toxic wastes and chronic diseases as a result of chromite mining, there is a tragic gap in the availability of 'scientific’ studies and data on the health hazards of mining in India. Occupational Safety and Health Administration, Odisha State Pollution Control Board and the Odisha Voluntary Health Association data were used to compile the possible occupational health hazards, hexavalent chromium exposure and diseases among Sukinda chromite mines workers. Studies were reviewed to determine the routes of exposure and possible mechanism of chromium induced carcinogenicity among the workers. Our studies suggest all forms of hexavalent chromium are regarded as carcinogenic to workers however the most important routes of occupational exposure to Cr (VI) are inhalation and dermal contact. This review article outlines the physical, chemical, biological and psychosocial occupational health hazards of chromite mining and associated metallurgical processes to monitor the mining environment as well as the miners exposed to these toxicants to foster a safe work environment. The authors anticipate that the outcome of this manuscript will have an impact on Indian chromite mining industry that will subsequently bring about improvements in work conditions, develop intervention experiments in occupational health and safety programs. PMID:21808494

Genotoxicity and carcinogenicity of acrylamide: a critical review.

PubMed

Carere, Angelo

2006-01-01

In 2002, public health concerns were raised by Swedish studies showing that relatively high levels of acrylamide were formed during the frying, roasting, or baking of a variety of foods, including potatoes, cereal products and coffee at temperatures above 120 degrees C. Acrylamide possesses a range of hazardous properties, the key effects being carcinogenicity, genotoxicity, neurotoxicity and reproductive toxicity. Acrylamide is clearly carcinogenic in studies in animals, in which it causes increased tumour incidence at a variety of sites. Although the mechanisms for tumour induction in experimental animals have not yet fully elucidated, the in vivo genotoxicity at gene and chromosome level in somatic and germ cells in rodents cannot be discounted from contributing to it. At this time, there is no information to indicate any significant difference between rodents and humans in sensitivity to cancer formation from acrylamide. The present available epidemiological studies of human industrial and accidental exposures have to be considered not suitable for use in the cancer risk assessment of acrylamide in food, due to several limitations. In reviewing the genotoxicity and carcinogenicity of acrylamide, the author has taken into account also the evaluations made by the IARC in 1994, the FAO/WHO in 2002 by the European Commission Scientific Committee on Food (SCF) in 2002 and by the Joint FAO/WHO Expert Committee on Food Additive (JECFA) in 2005.

Evaluation of a rat tracheal epithelial cell culture assay system to identify respiratory carcinogens

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steele, V.E.; Arnold, J.T.; Arnold, J.V.

1989-01-01

To evaluate a short-term epithelial cell assay system to detect respiratory carcinogens, primary cultures of rat tracheal epithelial cells were exposed to a series of 17 compounds and scored for morphologically transformed cell colonies 28 days later. The test compounds included known carcinogens and noncarcinogens in volatile or liquid form. Tracheal epithelial cells were isolate from F344 rats, plated onto collagen-coated dishes, and exposed to the test compounds on day 1 for 24 hours. At day 30 the cultures were fixed, stained, and scored for colonies having a density greater than 1,300 cells/mm{sup 2}. With standardized protocols, such colonies aremore » very infrequent in media and solvent control cultures. Concentration levels for each chemical were chosen over a range from nontoxic to toxic levels. Highly positive compounds in this assay included benzo(a)pyrene, benzo(l)aceanthrylene, 3-methylcholanthrene, and formaldehyde. Compounds which were negative in this assay included pyrene, benzo(e)pyrene, and 4-nitroquinoline-N-oxide. Examining the concordance of in vitro results with whole animal carcinogenesis studies revealed an accuracy of 88% with one false-positive and one false-negative compound. The results of these studies indicate that the rat tracheal epithelial cell assay may be useful in identifying potential respiratory carcinogens in our environment.« less

Studies on glyphosate-induced carcinogenicity in mouse skin: a proteomic approach.

PubMed

George, Jasmine; Prasad, Sahdeo; Mahmood, Zafar; Shukla, Yogeshwer

2010-03-10

Glyphosate is a widely used broad spectrum herbicide, reported to induce various toxic effects in non-target species, but its carcinogenic potential is still unknown. Here we showed the carcinogenic effects of glyphosate using 2-stage mouse skin carcinogenesis model and proteomic analysis. Carcinogenicity study revealed that glyphosate has tumor promoting activity. Proteomic analysis using 2-dimensional gel electrophoresis and mass spectrometry showed that 22 spots were differentially expressed (>2 fold) on glyphosate, 7, 12-dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) application over untreated control. Among them, 9 proteins (translation elongation factor eEF-1 alpha chain, carbonic anhydrase III, annexin II, calcyclin, fab fragment anti-VEGF antibody, peroxiredoxin-2, superoxide dismutase [Cu-Zn], stefin A3, and calgranulin-B) were common and showed similar expression pattern in glyphosate and TPA-treated mouse skin. These proteins are known to be involved in several key processes like apoptosis and growth-inhibition, anti-oxidant responses, etc. The up-regulation of calcyclin, calgranulin-B and down-regulation of superoxide dismutase [Cu-Zn] was further confirmed by immunoblotting, indicating that these proteins can be good candidate biomarkers for skin carcinogenesis induced by glyphosate. Altogether, these results suggested that glyphosate has tumor promoting potential in skin carcinogenesis and its mechanism seems to be similar to TPA. Copyright (c) 2009 Elsevier B.V. All rights reserved.

Mobile source air toxics mitigation measures.

DOT National Transportation Integrated Search

2013-10-01

In accordance with the Federal Highway Administration (FHWA) Interim Guidance Update on Mobile Source Air Toxic Analysis in NEPA Documents (September 30, 2009), transportation projects subject to the National Environmental Policy Act (NEPA) mus...

Toxic Release Inventory Chemicals by Groupings

EPA Pesticide Factsheets

The Toxics Release Inventory (TRI) makes available information for more than 600 toxic chemicals that are being used, manufactured, treated, transported, or released into the environment since 1987. EPA makes changes (additions, deletions, or changes in definition) to the TRI chemical list. As a result, the TRI list of reportable toxic chemicals can vary from year to year. EPA created groupings such as the core chemical lists (of 1988, 1991, 1995, 1998, 2000, and 2001) to facilitate year-to-year comparison based on a consistent set of reporting requirements and assure that changes in TRI release or other waste management amounts do not reflect the addition, deletion, or change in definition of reportable chemicals. EPA also created groupings of specific chemicals of interest by categories such as Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA), Hazardous Air Pollutants (HAPs), Metals, Newly Added TRI Chemicals in 1995, Occupational Safety and Health Administration (OSHA, Carcinogens), Persistent Bioaccumulative and Toxic (PBT) Chemicals, and Priority Chemicals.

Seeding materials: Health and safety considerations

NASA Technical Reports Server (NTRS)

Brown, R. D.

1985-01-01

The choice of a proper seeding material for laser velocimeters must include health and safety considerations. Failure to do so can lead to catastrophic results. All materials are toxic, and laser velocimeter seeding materials are no exception. Toxicity may be considered an inherent property of a given material. The manifestation of that property or the physiological response to the material is dependent on dose and exposure conditions. An approximate physiological classification of toxicity is given in tablular form. Toxicity in some situations is not necessarily the most restrictive factor in selection of materials. It is also very important to consider how the material is used so that actual exposure to the material in a damaging form can result. For example, nickel and cadmium are both extremely toxic as systemic poisons and in the case of nickel as a carcinogen. Seeding materials are dispersed in air under conditions that favor personnel exposure. Dispersal equipment is frequently if not normally manned, and personnel are often required to make frequent adjustments to assure proper operations.

Toxicity of lead: A review with recent updates

PubMed Central

Gupta, Deepesh; Tiwari, Archana

2012-01-01

Lead poisoning has been recognized as a major public health risk, particularly in developing countries. Though various occupational and public health measures have been undertaken in order to control lead exposure, cases of lead poisoning are still reported. Exposure to lead produces various deleterious effects on the hematopoietic, renal, reproductive and central nervous system, mainly through increased oxidative stress. These alterations play a prominent role in disease manifestations. Modulation of cellular thiols for protection against reactive oxygen species (ROS) has been used as a therapeutic strategy against lead poisoning. N-acetylcysteine, α-lipoic acid, vitamin E, quercetin and a few herbal extracts show prophylaxis against the majority of lead mediated injury in both in vitro and in vivo studies. This review provides a comprehensive account of recent updates describing health effects of lead exposure, relevant biomarkers and mechanisms involved in lead toxicity. It also updates the readers about recent advances in chelation therapy and newer therapeutic strategies, like nanoencapsulation, to treat lead induced toxic manifestations. PMID:23118587

Permitted Daily Exposure for Diisopropyl Ether as a Residual Solvent in Pharmaceuticals

PubMed Central

Evandri, Maria Grazia

2018-01-01

Solvents can be used in the manufacture of medicinal products provided their residual levels in the final product comply with the acceptable limits based on safety data. At worldwide level, these limits are set by the “Guideline Q3C (R6) on impurities: guideline for residual solvents” issued by the ICH. Diisopropyl ether (DIPE) is a widely used solvent but the possibility of using it in the pharmaceutical manufacture is uncertain because the ICH Q3C guideline includes it in the group of solvents for which “no adequate toxicological data on which to base a Permitted Daily Exposure (PDE) was found”. We performed a risk assessment of DIPE based on available toxicological data, after carefully assessing their reliability using the Klimisch score approach. We found sufficiently reliable studies investigating subchronic, developmental, neurological toxicity and carcinogenicity in rats and genotoxicity in vitro. Recent studies also investigated a wide array of toxic effects of gasoline/DIPE mixtures as compared to gasoline alone, thus allowing identifying the effects of DIPE itself. These data allowed a comprehensive toxicological evaluation of DIPE. The main target organs of DIPE toxicity were liver and kidney. DIPE was not teratogen and had no genotoxic effects, either in vitro or in vivo. However, it appeared to increase the number of malignant tumors in rats. Therefore, DIPE could be considered as a non-genotoxic animal carcinogen and a PDE of 0.98 mg/day was calculated based on the lowest No Observed Effect Level (NOEL) value of 356 mg/m3 (corresponding to 49 mg/kg/day) for maternal toxicity in developmental rat toxicity study. In a worst-case scenario, using an exceedingly high daily dose of 10 g/day, allowed DIPE concentration in pharmaceutical substances would be 98 ppm, which is in the range of concentration limits for ICH Q3C guideline class 2 solvents. This result might be considered for regulatory decisions. PMID:29686773

Reactive Metabolites in the Biotransformation of Molecules Containing a Furan Ring

PubMed Central

Peterson, Lisa A.

2012-01-01

Many xenobiotics containing a furan ring are toxic and/or carcinogenic. The harmful effects of these compounds require furan ring oxidation. This reaction generates an electrophilic intermediate. Depending on the furan ring substituents, the intermediate is either an epoxide or a cis-enedione with more ring substitution favoring epoxide formation. Either intermediate reacts with cellular nucleophiles such as protein or DNA to trigger toxicities. The reactivity of the metabolite determines which cellular nucleophiles are targeted. The toxicity of a particular furan is also influenced by the presence of competing metabolic pathways or efficient detoxification routes. GSH plays an important role in modulating the harmful effects of this class of compound by reacting with the reactive metabolite. However, this may not represent a detoxification step in all cases. PMID:23061605

Toxico-Cheminformatics: New and Expanding Public ...

EPA Pesticide Factsheets

High-throughput screening (HTS) technologies, along with efforts to improve public access to chemical toxicity information resources and to systematize older toxicity studies, have the potential to significantly improve information gathering efforts for chemical assessments and predictive capabilities in toxicology. Important developments include: 1) large and growing public resources that link chemical structures to biological activity and toxicity data in searchable format, and that offer more nuanced and varied representations of activity; 2) standardized relational data models that capture relevant details of chemical treatment and effects of published in vivo experiments; and 3) the generation of large amounts of new data from public efforts that are employing HTS technologies to probe a wide range of bioactivity and cellular processes across large swaths of chemical space. By annotating toxicity data with associated chemical structure information, these efforts link data across diverse study domains (e.g., ‘omics’, HTS, traditional toxicity studies), toxicity domains (carcinogenicity, developmental toxicity, neurotoxicity, immunotoxicity, etc) and database sources (EPA, FDA, NCI, DSSTox, PubChem, GEO, ArrayExpress, etc.). Public initiatives are developing systematized data models of toxicity study areas and introducing standardized templates, controlled vocabularies, hierarchical organization, and powerful relational searching capability across capt

Biological Networks for Predicting Chemical Hepatocarcinogenicity Using Gene Expression Data from Treated Mice and Relevance across Human and Rat Species

PubMed Central

Thomas, Reuben; Thomas, Russell S.; Auerbach, Scott S.; Portier, Christopher J.

2013-01-01

Background Several groups have employed genomic data from subchronic chemical toxicity studies in rodents (90 days) to derive gene-centric predictors of chronic toxicity and carcinogenicity. Genes are annotated to belong to biological processes or molecular pathways that are mechanistically well understood and are described in public databases. Objectives To develop a molecular pathway-based prediction model of long term hepatocarcinogenicity using 90-day gene expression data and to evaluate the performance of this model with respect to both intra-species, dose-dependent and cross-species predictions. Methods Genome-wide hepatic mRNA expression was retrospectively measured in B6C3F1 mice following subchronic exposure to twenty-six (26) chemicals (10 were positive, 2 equivocal and 14 negative for liver tumors) previously studied by the US National Toxicology Program. Using these data, a pathway-based predictor model for long-term liver cancer risk was derived using random forests. The prediction model was independently validated on test sets associated with liver cancer risk obtained from mice, rats and humans. Results Using 5-fold cross validation, the developed prediction model had reasonable predictive performance with the area under receiver-operator curve (AUC) equal to 0.66. The developed prediction model was then used to extrapolate the results to data associated with rat and human liver cancer. The extrapolated model worked well for both extrapolated species (AUC value of 0.74 for rats and 0.91 for humans). The prediction models implied a balanced interplay between all pathway responses leading to carcinogenicity predictions. Conclusions Pathway-based prediction models estimated from sub-chronic data hold promise for predicting long-term carcinogenicity and also for its ability to extrapolate results across multiple species. PMID:23737943

Textile industry and occupational cancer.

PubMed

Singh, Zorawar; Chadha, Pooja

2016-01-01

Thousands of workers are engaged in textile industry worldwide. Textile industry involves the use of different kinds of dyes which are known to possess carcinogenic properties. Solvents used in these industries are also associated with different health related hazards including cancer. In previous studies on textile and iron industries, the authors have reported genotoxicity among them and observed occurrence of cancer deaths among textile industry workers. Thus, an attempt has been made to compile the studies on the prevalence of different types of cancers among textile industry workers. A wide literature search has been done for compiling the present paper. Papers on cancer occurrence among textile industry workers have been taken from 1976 to 2015. A variety of textile dyes and solvents, many of them being carcinogenic, are being used worldwide in the textile industry. The textile industry workers are therefore, in continuous exposure to these dyes, solvents, fibre dusts and various other toxic chemicals. The present study evaluates the potential of different chemicals and physical factors to be carcinogenic agents among occupationally exposed workers by going through various available reports and researches. Papers were collected using different databases and a number of studies report the association of textile industry and different types of cancer including lung, bladder, colorectal and breast cancer. After going through the available reports, it can be concluded that workers under varied job categories in textile industries are at a higher risk of developing cancer as various chemicals used in the textile industry are toxic and can act as potential health risk in inducing cancer among them. Assessing the cancer risk at different job levels in textile industries may be found useful in assessing the overall risk to the workers and formulating the future cancer preventive strategies.

Disposition of xenobiotic chemicals and metabolites in marine organisms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Varanasi, U.; Stein, J.E.

1991-01-01

Studies with several bottom fish species from urban waterways show that of the identified xenobiotic chemicals in bottom sediments, polycyclic aromatic hydrocarbons (PAHs) are the most strongly associated with the prevalence of liver lesions, including neoplasms. Accordingly, there is concern about the transfer of contaminants, such as PAHs, from aquatic species to humans. Because PAHs exert their toxicity only after being biotransformed, increasing attention has been focused on the ability of aquatic organisms to metabolize these chemicals. Overall, the results of both laboratory and field studies show that generally low levels of a few low molecular weight PAHs may bemore » present in edible tissue of fish from contaminated areas and that high molecular weight PAHs, such as the carcinogen benzo(a)pyrene, will rarely be detected because of extensive metabolism. Additionally, the results from a few studies suggest that even though interactions between xenobiotics can affect both biochemical and physiological systems to alter the disposition of PAHs in fish, these interactions do not markedly change the relative proportions of metabolites to parent PAH in tissues. Thus, these studies clearly demonstrate that to obtain some insight into the questions of whether there is any risk to human health from consuming fish and crustaceans from urban areas, techniques must be developed that measure metabolites of carcinogens, such as PAHs, in edible tissue. Initial attempts may focus on semiquantitative methods that permit rapid assessment of the level of metabolites in edible tissues of fish and crustaceans from many urban areas. Based on information from such screening studies, further refinement in methodology leading to identification of specific compounds may be needed because certain metabolites may not be as toxic or carcinogenic as others.« less

Biological networks for predicting chemical hepatocarcinogenicity using gene expression data from treated mice and relevance across human and rat species.

PubMed

Thomas, Reuben; Thomas, Russell S; Auerbach, Scott S; Portier, Christopher J

2013-01-01

Several groups have employed genomic data from subchronic chemical toxicity studies in rodents (90 days) to derive gene-centric predictors of chronic toxicity and carcinogenicity. Genes are annotated to belong to biological processes or molecular pathways that are mechanistically well understood and are described in public databases. To develop a molecular pathway-based prediction model of long term hepatocarcinogenicity using 90-day gene expression data and to evaluate the performance of this model with respect to both intra-species, dose-dependent and cross-species predictions. Genome-wide hepatic mRNA expression was retrospectively measured in B6C3F1 mice following subchronic exposure to twenty-six (26) chemicals (10 were positive, 2 equivocal and 14 negative for liver tumors) previously studied by the US National Toxicology Program. Using these data, a pathway-based predictor model for long-term liver cancer risk was derived using random forests. The prediction model was independently validated on test sets associated with liver cancer risk obtained from mice, rats and humans. Using 5-fold cross validation, the developed prediction model had reasonable predictive performance with the area under receiver-operator curve (AUC) equal to 0.66. The developed prediction model was then used to extrapolate the results to data associated with rat and human liver cancer. The extrapolated model worked well for both extrapolated species (AUC value of 0.74 for rats and 0.91 for humans). The prediction models implied a balanced interplay between all pathway responses leading to carcinogenicity predictions. Pathway-based prediction models estimated from sub-chronic data hold promise for predicting long-term carcinogenicity and also for its ability to extrapolate results across multiple species.

Children’s Exposure to Secondhand and Thirdhand Smoke Carcinogens and Toxicants in Homes of Hookah Smokers

PubMed Central

Daffa, Reem M.; Liles, Sandy; Jackson, Sheila R.; Kassem, Noura O.; Younis, Maram A.; Mehta, Setoo; Chen, Menglan; Jacob, Peyton; Carmella, Steve G.; Chatfield, Dale A.; Benowitz, Neal L.; Matt, Georg E.; Hecht, Stephen S.; Hovell, Melbourne F.

2014-01-01

Introduction: We examined homes of hookah-only smokers and nonsmokers for levels of indoor air nicotine (a marker of secondhand smoke) and indoor surface nicotine (a marker of thirdhand smoke), child uptake of nicotine, the carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and the toxicant acrolein by analyzing their corresponding metabolites cotinine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and NNAL-glucuronides (total NNAL) and 3-hydroxypropylmercapturic acid. Methods: Data were collected at 3 home visits during a 7-day study period from a convenience sample of 24 households with a child 5 years or younger. Three child urine samples and 2 air and surface samples from the living room and the child bedroom were taken in homes of nonsmokers (n = 5) and hookah-only smokers (n = 19) comprised of daily hookah smokers (n = 8) and weekly/monthly hookah smokers (n = 11). Results: Nicotine levels in indoor air and on surfaces in the child bedrooms in homes of daily hookah smokers were significantly higher than in homes of nonsmokers. Uptake of nicotine, NNK, and acrolein in children living in daily hookah smoker homes was significantly higher than in children living in nonsmoker homes. Uptake of nicotine and NNK in children living in weekly/monthly hookah smoker homes was significantly higher than in children living in nonsmoker homes. Conclusions: Our data provide the first evidence for uptake of nicotine, the tobacco-specific lung carcinogen NNK, and the ciliatoxic and cardiotoxic agent acrolein in children living in homes of hookah smokers. Our findings suggest that daily and occasional hookah use in homes present a serious, emerging threat to children’s long-term health. PMID:24590387

Western oil shale development: a technology assessment. Volume 8. Health effects of oil shale development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rotariu, G.J.

1982-02-01

Information on the potential health effects of a developing oil shale industry can be derived from two major sources: (1) the historical experience in foreign countries that have had major industries; and (2) the health effects research that has been conducted in the US in recent years. The information presented here is divided into two major sections: one dealing with the experience in foreign countries and the second dealing with the more recent work associated with current oil shale development in the US. As a result of the study, several observations can be made: (1) most of the current andmore » historical data from foreign countries relate to occupational hazards rather than to impacts on regional populations; (2) neither the historical evidence from other countries nor the results of current research have shown pulmonary neoplasia to be a major concern, however, certain types of exposure, particularly such mixed source exposures as dust/diesel or dust/organic-vapor have not been adequately studied and the lung cancer question is not closed; (3) the industry should be alert to the incidence of skin disease in the industrial setting, however, automated techniques, modern industrial hygiene practices and realistic personal hygiene should greatly reduce the hazards associated with skin contact; and (4) the entire question of regional water contamination and any resultant health hazard has not been adequately addressed. The industrial practice of hydrotreating the crude shale oil will diminish the carcinogenic hazard of the product, however, the quantitative reduction of biological activity is dependent on the degree of hydrotreatment. Both Soviet and American experimentalists have demonstrated a correlation betweed carcinogenicity/toxicity and retorting temperature; the higher temperatures producing the more carcinogenic or toxic products.« less

Evidence of carcinogenicity in humans of water-soluble nickel salts

PubMed Central

2010-01-01

Background Increased risks of nasal cancer and lung cancer in nickel refiners have been investigated scientifically and discussed since they were detected in the 1930s. Nickel compounds are considered to be the main cause of the cancer excess. Parts of the nickel producing industry and their consultants oppose the classification of water-soluble nickel salts as human carcinogens, and argue that the risk in exposed workers should be ascribed to other occupational exposures and smoking. Discussion Respiratory cancer risks in Welsh, Finnish, and Norwegian nickel refiners add to the evidence of carcinogenicity of water-soluble nickel. In Norwegian refiners, the first epidemiological study in 1973 identified high risks of lung cancer and nasal cancer among long-term electrolysis workers. Risk analyses based on exposure estimates developed in the 1980s supported the view that water-soluble nickel compounds were central in the development of cancer. Recently, new exposure estimates were worked out for the same cohort based on personal monitoring of total nickel and chemical determination of four forms of nickel. Additional data have been collected on life-time smoking habits, and on exposure to arsenic, asbestos, sulphuric acid mists, cobalt, and occupational lung carcinogens outside the refinery. After adjustment for these potential confounding exposures in case-control analyses, the risk pattern added to the evidence of an important role of water-soluble nickel compounds as causes of lung cancer. These Norwegian cancer studies rely on national Cancer Registry data, considered close to complete from 1953 onwards; and on National Population Register data continuously updated with mortality and emigration. Canadian mortality studies--perceived to offer the strongest support to the industry position not to recognise carcinogenicity of water-soluble nickel--appear to suffer from limitations in follow-up time, loss to follow-up, absence of risk analysis with individual exposure estimates, no confounder control, and a likely underestimation of cancer mortality. Conclusions Rejection to recognise water-soluble nickel as a human carcinogen seems to contradict material epidemiological evidence that demonstrates a strong association between water-soluble nickel compounds and risks of lung cancer and nasal cancer. Independent international scientific bodies have classified nickel compounds as carcinogenic to humans, inclusive of water-soluble nickel. PMID:20377901

Progress Update: Stack Project Complete

ScienceCinema

Cody, Tom

2017-12-12

Progress update from the Savannah River Site. The 75 foot 293 F Stack, built for plutonium production, was cut down to size in order to prevent injury or release of toxic material if the structure were to collapse due to harsh weather.

Determination of primary aromatic amines in cold water extract of coloured paper napkin samples by liquid chromatography-tandem mass spectrometry.

PubMed

Yavuz, Oguzhan; Valzacchi, Sandro; Hoekstra, Eddo; Simoneau, Catherine

2016-06-01

The aim of this study was the optimisation of a multi-analyte method for the analysis of primary aromatic amines (PAAs) from napkins in order to support official controls and food safety. We developed a UHPLC-MS/MS method for the simultaneous determination of 36 toxicologically relevant PAAs for paper and board. Good regression coefficients of the calibration curves in a range of 0.992-0.999 and reproducibilities in a range of 2.3-15% were obtained. Limits of detections (LODs) were in the range of 0.03-1.4 µg l(-1) and recoveries were in a range of 21-110% for all the amines. A total of 93 coloured paper napkin samples from different European countries were bought and extracted with water to determine the PAAs. The results showed that 42 of 93 samples contained at least one PAA. More than half of the detected PAAs are considered as toxic, carcinogenic or probably carcinogenic to humans by the International Agency for Research on Cancer (IARC), or are classified as such in the European Union legislation on chemicals. Summed concentrations of PAAs in seven samples were higher than 10 µg l(-1), the limit of summed PAA in the European Union plastic food contact material regulation. Also, eight PAAs, classified as Category 1A and 1B carcinogen in the European Union legislation of chemicals, were detected at concentrations higher than 2 µg l(-1), exceeding the limit proposed by the Federal Institute for Risk Assessment in Germany. Aniline (n = 14) was most frequently present in higher concentrations followed by o-toluidine, o-anisidine, 2,4-dimethylaniline and 4-aminoazobenzene. Red, orange, yellow and multicoloured paper napkins contained the highest concentrations of total PAAs (> 10 µg l(-1)). Although the European Union has not harmonised the legislation of paper and board materials and, thus, there is no specific migration limit for PAAs from paper napkins, the present study showed that coloured paper napkins can contain toxic and carcinogenic PAAs at concentrations that are relevant for monitoring.

MECHANISTIC CONSIDERATIONS FOR HUMAN RELEVANCE OF CANCER HAZARD OF DI(2-ETHYLHEXYL) PHTHALATE

PubMed Central

Rusyn, Ivan; Corton, J. Christopher

2012-01-01

Di(2-ethylhexyl) phthalate (DEHP) is a peroxisome proliferator agent that is widely used as a plasticizer to soften polyvinylchloride plastics and non-polymers. Both occupational (e.g., by inhalation during its manufacture and use as a plasticizer of polyvinylchloride) and environmental (medical devices, contamination of food, or intake from air, water and soil) routes of exposure to DEHP are of concern for human health. There is sufficient evidence for carcinogenicity of DEHP in the liver in both rats and mice; however, there is little epidemiological evidence on possible associations between exposure to DEHP and liver cancer in humans. Data are available to suggest that liver is not the only target tissue for DEHP-associated toxicity and carcinogenicity in both humans and rodents. The debate regarding human relevance of the findings in rats or mice has been informed by studies on the mechanisms of carcinogenesis of the peroxisome proliferator class of chemicals, including DEHP. Important additional mechanistic information became available in the past decade, including, but not limited to, sub-acute, sub-chronic and chronic studies with DEHP in peroxisome proliferator-activated receptor (PPAR) α-null mice, as well as experiments utilizing several transgenic mouse lines. Activation of PPARα and the subsequent downstream events mediated by this transcription factor represent an important mechanism of action for DEHP in rats and mice. However, additional data from animal models and studies in humans exposed to DEHP from the environment suggest that multiple molecular signals and pathways in several cell types in the liver, rather than a single molecular event, contribute to the cancer in rats and mice. In addition, the toxic and carcinogenic effects of DEHP are not limited to liver. The International Agency for Research on Cancer working group concluded that the human relevance of the molecular events leading to cancer elicited by DEHP in several target tissues (e.g., liver and testis) in rats and mice can not be ruled out and DEHP was classified as possibly carcinogenic to humans (Group 2B). PMID:22198209

Zinc hazards to plants and animals with emphasis on fishery and wildlife resources

USGS Publications Warehouse

Eisler, R.; Cheremisinoff, Paul N.

1997-01-01

Ecological and toxicological aspects of zinc in the environment are reviewed with emphasis on natural resources. Subtopics include sources and uses; chemical and biochemical properties; carcinogenicity, mutagenicity, teratogenicity; background concentrations in biological and nonbiological compartments; effects of zinc deficiency; toxic and sublethal effects on terrestrial plants and invertebrates, aquatic organisms, birds, and mammals; and recommendations for the protection of sensitive resources.

Process for detoxifying coal tars

DOEpatents

Longwell, John P.; Peters, William A.

1983-01-01

A process for treating liquid hydrocarbons to remove toxic, mutagenic and/or carcinogenic aromatic hydrocarbons comprises feeding the hydrocarbons into a reactor where vapors are thermally treated in contact with a catalyst consisting essentially of calcium oxide or a calcium oxide containing mineral. Thermally treating liquid hydrocarbons in contact with calcium oxide preferentially increases the cracking of aromatics thus producing a product having a reduced amount of aromatic compounds.

Using kepone to exemplify the importance of natural variability in estimating exposure to toxic chemicals from aquatic environments

Treesearch

Robert J. Huggett

2000-01-01

Kepone, decachlorooctahydro-l, 3, 4-metheno-2H-cyclobuta (cd) pentalen-2-one, is a known mammalian carcinogen. From at least 1967 to 1975 when production stopped, it contaminated the Chesapeake Bay. Action levels for kepone in seafood were established by the U.S. Environmental Protection Agency, and various species of finfish, oysters, Crassostrea virginica...

Plastic Media Blasting Data Gathering Study

DTIC Science & Technology

1986-12-01

products of organic compounds containing the amino group (-NH 2 ) and an aldehyde. The better known members of this group are urea formaldehyde (a...suspected carcinogen) and melamine formaldehyde . The actual composition and toxicity of the dust from the various operations must be collected and...blasting is a paint removal technique in which small, granular amino thermoset or unsaturated polyester resins (plastic beads) are forced at high

CHARACTERISTICS AND TOXICITY OF THE DRINKING WATER DISINFECTION BY-PRODUCT 3-CHLORO-4(DICHLOROMETHYL)-5-HYDROXY-2[5H]-FURANONE (MX) TO MEDAKA (ORYZIAS LATIPES)

EPA Science Inventory

The compound 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone, also known as MX, is a by-product of wood pulp manufacture and a contaminant of chlorinated drinking and sewage water. MX has recently been shown to be carcinogenic to rodents. However, no data exist for its effec...

Use of UHPLC high-resolution Orbitrap mass spectrometry to investigate the genes involved in the production of secondary metabolites in Aspergillus flavus

USDA-ARS?s Scientific Manuscript database

The fungus Aspergillus flavus is known for its ability to produce the toxic and carcinogenic aflatoxins in food and feed. While aflatoxins are of most concern, A. flavus is predicted to be capable of producing many more metabolites based on a study of its complete genome sequence. Some of these meta...

CHARACTERIZATION OF STABLE BENZOLALPYRENE-7,8-QUINONE-DNA ADDUCTS IN CALF THYMUS DNA AND POLYDEOXYNUCLEOTIDES

EPA Science Inventory

Bcnzo[a]pyrene-7,8-dione (BPQ) is a reactive aldo-keto reductase-mediated product of B[a]P-7,8-diol, a major P450/epoxide hydrolase metabolite of the multi-species carcinogen, B[a]P. The role of BPQ in B[a]P's genotoxicity and carcinogenesis is evolving. Toxicity pathways involvi...

Flow Cytometric Analysis of Hepatocytes from Normal, PFDA, and PH/DEN/ PB-Treated Rats

DTIC Science & Technology

1989-12-31

SUB-GROUP’ Perfluorodecanoic acid ( PFDA ); hepatocarcinogenesis; preneoplastic lesions; flow cytometry; imunotoxicitYyc3 1%&STRACT (Continue on...effects of perfluorodecanoic acid ( PFDA ). Flow cytometric evaluation of hepatocytes from PEDA-treated rats revealed an increase in size and granularity...was designed to generate preliminary information regarding the toxic and potential carcinogenic effects of perfluorodecanoic acid ( PFDA ) on rat

Autoclave sterilization produces acrylamide in rodent diets: implications for toxicity testing.

PubMed

Twaddle, Nathan C; Churchwell, Mona I; McDaniel, L Patrice; Doerge, Daniel R

2004-06-30

Acrylamide (AA) is a neurotoxic and carcinogenic contaminant that is formed during the cooking of starchy foods. Assessment of human risks from toxicants is routinely performed using laboratory rodents, and such testing requires careful control of unintended exposures, particularly through the diet. This study describes an analytical method based on liquid chromatography with electrospray tandem mass spectrometry that was used to measure endogenous AA in rodent diets and to survey a number of commercial products for contamination. Method sensitivity permitted accurate quantification of endogenous levels of AA in raw diets below 20 ppb. Autoclaving a standard rodent diet (NIH-31) increased the AA content 14-fold, from 17 to 240 ppb. A nutritionally equivalent diet that was sterilized by irradiation was found to contain approximately 10 ppb of AA (NIH-31IR). A toxicokinetic study of AA and its epoxide metabolite, glycidamide, was performed by switching mice from NIH-31IR to the autoclaved diet for a 30 min feeding period (average AA dose administered was 4.5 microg/kg of body weight). The concentrations of AA and glycidamide were measured in serum collected at various times. The elimination half-lives and the areas under the respective concentration-time curves were similar for AA and glycidamide. Mice maintained on autoclaved NIH-31 diet, but otherwise untreated, showed elevated steady state levels of a glycidamide-derived DNA adduct in liver relative to mice maintained on the irradiated diet. This study demonstrates that a heat sterilization procedure used in laboratory animal husbandry (i.e., autoclaving) can lead to the formation of significant levels of AA in basal diets used for toxicity testing. AA in rodent diets is bioavailable, is distributed to tissues, and is metabolically activated to a genotoxic metabolite, which produces quantifiable cumulative DNA damage. Although the contribution of endogenous AA to the incidence of tumors in multiple organs of rodents otherwise untreated in chronic carcinogenicity bioassays (i.e., control groups) is not known, the reduction of endogenous AA through the use of a suitable irradiated diet was deemed to be critical for ongoing studies of AA carcinogenicity and neurotoxicity.

Occurrence and Control of Genotoxins in Drinking Water: A Monitoring Proposal

PubMed Central

Ceretti, Elisabetta; Moretti, Massimo; Zerbini, Ilaria; Villarini, Milena; Zani, Claudia; Monarca, Silvano; Feretti, Donatella

2016-01-01

Many studies have shown the presence of numerous organic genotoxins and carcinogens in drinking water. These toxic substances derive not only from pollution, but also from the disinfection treatments, particularly when water is obtained from surface sources and then chlorinated. Most of the chlorinated compounds in drinking water are nonvolatile and are difficult to characterize. Thus, it has been proposed to study such complex mixtures using short-term genotoxicity tests predictive of carcinogenic activity. Mutagenicity of water before and after disinfection has mainly been studied by the Salmonella/microsome (Ames test); in vitro genotoxicity tests have also been performed in yeasts and mammalian cells; in situ monitoring of genotoxins has also been performed using complete organisms such as aquatic animals or plants (in vivo). The combination of bioassay data together with results of chemical analyses would give us a more firm basis for the assessment of human health risks related to the consumption of drinking water. Tests with different genetic end-points complement each other with regard to sensitivity toward environmental genotoxins and are useful in detecting low genotoxicity levels which are expected in drinking water samples. Significance for public health The provision of a safe drinking water is an important public health problem. Many studies have shown the presence of numerous genotoxins and carcinogens in drinking water. These toxic substances derive not only from pollution, but also from the disinfection treatments, particularly when water is obtained from surface sources and then chlorinated. The potential health risks of disinfection by-products (DBPs) from drinking water include cancer and adverse reproductive outcomes. People are exposed to disinfected drinking/shower/bathing water as a mixture of at least 600 identified DBPs and other toxic compounds via dermal, inhalation, and ingestion routes. Many of these substances are present in trace concentration, hardly detectable by chemical standard analysis. The monitoring of environmental genotoxins by short-term bioassays could allow a better evaluation of the global human exposure to water genotoxins and could help health officers and drinking water managers to reduce genotoxic hazards and distribute high quality drinking water. PMID:28083525

Ganga water pollution: A potential health threat to inhabitants of Ganga basin.

PubMed

Dwivedi, Sanjay; Mishra, Seema; Tripathi, Rudra Deo

2018-05-18

The water quality of Ganga, the largest river in Indian sub-continent and life line to hundreds of million people, has severely deteriorated. Studies have indicated the presence of high level of carcinogenic elements in Ganga water. We performed extensive review of sources and level of organic, inorganic pollution and microbial contamination in Ganga water to evaluate changes in the level of various pollutants in the recent decade in comparison to the past and potential health risk for the population through consumption of toxicant tainted fishes in Ganga basin. A systematic search through databases, specific websites and reports of pollution regulatory agencies was conducted. The state wise level of contamination was tabulated along the Ganga river. We have discussed the major sources of various pollutants with particular focus on metal/metalloid and pesticide residues. Bioaccumulation of toxicants in fishes of Ganga water and potential health hazards to humans through consumption of tainted fishes was evaluated. The level of pesticides in Ganga water registered a drastic reduction in the last decade (i.e. after the establishment of National Ganga River Basin Authority (NGRBA) in 2009), still the levels of some organochlorines are beyond the permissible limits for drinking water. Conversely the inorganic pollutants, particularly carcinogenic elements have increased several folds. Microbial contamination has also significantly increased. Hazard quotient and hazard index indicated significant health risk due to metal/metalloid exposure through consumption of tainted fishes from Ganga. Target cancer risk assessment showed high carcinogenic risk from As, Cr, Ni and Pb as well as residues of DDT and HCHs. Current data analysis showed that Ganga water quality is deteriorating day by day and at several places even in upper stretch of Ganga the water is not suitable for domestic uses. Although there is positive impact of ban on persistent pesticides with decreasing trend of pesticide residues in Ganga water, the increasing trend of trace and toxic elements is alarming and the prolong exposure to polluted Ganga water and/or consumption of Ganga water fishes may cause serious illness including cancer. Copyright © 2018 Elsevier Ltd. All rights reserved.

Genome-Wide Functional and Stress Response Profiling Reveals Toxic Mechanism and Genes Required for Tolerance to Benzo[a]pyrene in S. cerevisiae

PubMed Central

O’Connor, Sean Timothy Francis; Lan, Jiaqi; North, Matthew; Loguinov, Alexandre; Zhang, Luoping; Smith, Martyn T.; Gu, April Z.; Vulpe, Chris

2012-01-01

Benzo[a]pyrene (BaP) is a ubiquitous, potent, and complete carcinogen resulting from incomplete organic combustion. BaP can form DNA adducts but other mechanisms may play a role in toxicity. We used a functional toxicology approach in S. cerevisiae to assess the genetic requirements for cellular resistance to BaP. In addition, we examined translational activities of key genes involved in various stress response pathways. We identified multiple genes and processes involved in modulating BaP toxicity in yeast which support DNA damage as a primary mechanism of toxicity, but also identify other potential toxicity pathways. Gene ontology enrichment analysis indicated that DNA damage and repair as well as redox homeostasis and oxidative stress are key processes in cellular response to BaP suggesting a similar mode of action of BaP in yeast and mammals. Interestingly, toxicant export is also implicated as a potential novel modulator of cellular susceptibility. In particular, we identified several transporters with human orthologs (solute carrier family 22) which may play a role in mammalian systems. PMID:23403841

Inhibition of autophagy promotes CYP2E1-dependent toxicity in HepG2 cells via elevated oxidative stress, mitochondria dysfunction and activation of p38 and JNK MAPK☆

PubMed Central

Wu, Defeng; Cederbaum, Arthur I.

2013-01-01

Autophagy has been shown to be protective against drug and alcohol-induced liver injury. CYP2E1 plays a role in the toxicity of ethanol, carcinogens and certain drugs. Inhibition of autophagy increased ethanol-toxicity and accumulation of fat in wild type and CYP2E1 knockin mice but not in CYP2E1 knockout mice as well as in HepG2 cells expressing CYP2E1 (E47 cells) but not HepG2 cells lacking CYP2E1 (C34 cells). The goal of the current study was to evaluate whether modulation of autophagy can affect CYP2E1-dependent cytotoxicity in the E47 cells. The agents used to promote CYP2E1 –dependent toxicity were a polyunsaturated fatty acid, arachidonic acid (AA), buthionine sulfoximine (BSO), which depletes GSH, and CCl4, which is metabolized to the CCl3 radical. These three agents produced a decrease in E47 cell viability which was enhanced upon inhibition of autophagy by 3-methyladenine (3-MA) or Atg 7 siRNA. Toxicity was lowered by rapamycin which increased autophagy and was much lower to the C34 cells which do not express CYP2E1. Toxicity was mainly necrotic and was associated with an increase in reactive oxygen production and oxidative stress; 3-MA increased while rapamycin blunted the oxidative stress. The enhanced toxicity and ROS formation produced when autophagy was inhibited was prevented by the antioxidant N-Acetyl cysteine. AA, BSO and CCl4 produced mitochondrial dysfunction, lowered cellular ATP levels and elevated mitochondrial production of ROS. This mitochondrial dysfunction was enhanced by inhibition of autophagy with 3-MA but decreased when autophagy was increased by rapamycin. The mitogen activated protein kinases p38 MAPK and JNK were activated by AA especially when autophagy was inhibited and chemical inhibitors of p38 MAPK and JNK lowered the elevated toxicity of AA produced by 3-MA. These results show that autophagy was protective against the toxicity produced by several agents known to be activated by CYP2E1. Since CYP2E1 plays an important role in the toxicity of ethanol, drugs and carcinogens and is activated under various pathophysiological conditions such as diabetes, NASH and obesity, attempts to stimulate autophagy may be beneficial in preventing/lowering CYP2E1/ethanol liver injury. PMID:24273738

Update on the DNT In Vitro Alternative Methods Project at the USEPA

EPA Science Inventory

Current approaches to toxicity testing rely heavily on the use of animals, can cost millions of dollars and can take years to complete for a single chemical. To implement the predictive toxicity testing envisioned in the NAS report on Toxicity Testing in the 21st century, rapid a...

Chemometric evaluation of heavy metal pollutions in Patna region of the Ganges alluvial plain, India: implication for source apportionment and health risk assessment.

PubMed

Devi, Ningombam Linthoingambi; Yadav, Ishwar Chandra

2018-03-28

While metal pollution and distribution in soil are well documented for many countries, the situation is more serious in developing countries because of the rapid increase in industrialization and urbanization during last decades. Although it is well documented in developed countries, data about substantial metal pollution in Indian soil, especially in eastern Ganges alluvial plain (GAP), are limited. In this study, eight different blocks of Patna district located in eastern GAP were selected to investigate the contamination, accumulation, and sources of metals in surface soil considering different land use types. Additionally, human health risk assessment was estimated to mark the potential carcinogenic and non-carcinogenic effect of metals in soil. The concentration of all metals (except Pb) in soil was below the Indian standard limit of the potential toxic element for agricultural soil. Pb was the most abundant in soil, followed by Zn and Cu, and accounted for 52, 33 and 8% of the total metal. In terms of land use types, roadside soil detected higher concentrations of all metals, followed by park/grassland soil. Principal component analysis results indicated traffic pollution and industrial emissions are the major sources of heavy metals in soil. This was further confirmed by strong inter-correlation of heavy metals (Cd, Cr, Ni, Cu and Pb). Human health risk assessment results indicated ingestion via soil as the primary pathway of heavy metal exposure to both adults and children population. The estimated hazard index was highest for Pb, suggesting significant non-carcinogenic effect to both adults and children population. The children were more prone to the non-carcinogenic effect of Pb than adults. However, relatively low cancer risk value estimated for all metals suggested non-significant carcinogenic risk in the soil.

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.

PubMed

Liu, Shujie; Kawamoto, Taisuke; Morita, Osamu; Yoshinari, Kouichi; Honda, Hiroshi

2017-03-01

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. Copyright © 2017 Elsevier Inc. All rights reserved.

Report on carcinogens monograph on 1-bromopropane.

PubMed

2013-09-01

The National Toxicology Program conducted a cancer evaluation on 1 bromopropane for possible listing in the Report on Carcinogens (RoC). The cancer evaluation is captured in the RoC monograph, which was peer reviewed in a public forum. The monograph consists of two components: (Part 1) the cancer evaluation, which reviews the relevant scientific information, assesses its quality, applies the RoC listing criteria to the scientific information, and provides the NTP recommendation for listing status for 1 bromopropane in the RoC, and (Part 2) the substance profile proposed for the RoC, containing the NTP's listing status recommendation, a summary of the scientific evidence considered key to reaching that decision, and data on properties, use, production, exposure, and Federal regulations and guidelines to reduce exposure to 1-bromopropane. This monograph provides an assessment of the available scientific information on 1 bromopropane, including human exposure and properties, disposition and toxicokinetics, cancer studies in experimental animals, and studies of mechanisms and other related effects, including relevant toxicological effects, genetic toxicology, and mechanisms of carcinogenicity. From this assessment, the NTP recommended that 1 bromopropane be listed as reasonably anticipated to be a human carcinogen in the RoC based on sufficient evidence from studies in experimental animals, which found inhalation exposure to 1-bromopropane caused skin tumors in male rats, large intestine tumors in female and male rats, and lung tumors in female mice. Also noted was that 1 bromopropane, either directly or via reactive metabolites, caused molecular alterations that typically are associated with carcinogenesis, including genotoxicity, oxidative stress, and glutathione depletion. These alterations, observed in mainly in vitro and toxicity studies in rodents, are relevant to possible mechanisms of human carcinogenicity and support the relevance of the cancer studies in experimental animals to humans.

Prostate cancer and toxicity from critical use exemptions of methyl bromide: Environmental protection helps protect against human health risks

PubMed Central

2012-01-01

Background Although ozone-depleting methyl bromide was destined for phase-out by 2005, it is still widely applied as a consequence of various critical-use-exemptions and mandatory international regulations aiming to restrict the spread of pests and alien species (e.g. in globalized transport and storage). The withdrawal of methyl bromide because of its environmental risk could fortuitously help in the containment of its human toxicity. Methods We performed a systematic review of the literature, including in vitro toxicological and epidemiological studies of occupational and community exposure to the halogenated hydrocarbon pesticide methyl bromide. We focused on toxic (especially chronic) or carcinogenic effects from the use of methyl bromide, on biomonitoring data and reference values. Eligible epidemiological studies were subjected to meta-analysis. Results Out of the 542 peer reviewed publications between 1990-2011, we found only 91 referring to toxicity of methyl bromide and 29 using the term "carcinogenic", "neoplastic" or "mutagenic". Several studies provide new additional data pertaining to the mechanistic aspects of methyl bromide toxicity. Few studies have performed a detailed exposure assessment including biomonitoring. Three evaluated epidemiological studies assessed a possible association between cancer and methyl bromide. Overall, exposure to methyl bromide is associated with an increased risk of prostate cancer OR, 1.21; 95% CI (0,98-1.49), P = 0.076. Two epidemiological studies have analyzed environmental, non-occupational exposure to methyl bromide providing evidence for its health risk to the general public. None of the epidemiological studies addressed its use as a fumigant in freight containers, although recent field and case reports do refer to its toxic effects associated with its use in shipping and storage. Conclusions Both the epidemiological evidence and toxicological data suggest a possible link between methyl bromide exposure and serious health problems, including prostate cancer risk from occupational and community exposure. The environmental risks of methyl bromide are not in doubt, but also its health risks, especially for genetically predisposed subjects, should not be underestimated. PMID:22284215

2005 v4.3 Technical Support Document

EPA Pesticide Factsheets

Emissions Modeling for the Final Mercury and Air Toxics Standards Technical Support Document describes how updated 2005 NEI, version 2 emissions were processed for air quality modeling in support of the final Mercury and Air Toxics Standards (MATS).

Genotoxicity and potential carcinogenicity of cyanobacterial toxins - a review.

PubMed

Zegura, Bojana; Straser, Alja; Filipič, Metka

2011-01-01

The occurrence of cyanobacterial blooms has increased significantly in many regions of the world in the last century due to water eutrophication. These blooms are hazardous to humans, animals, and plants due to the production of cyanotoxins, which can be classified in five different groups: hepatotoxins, neurotoxins, cytotoxins, dermatotoxins, and irritant toxins (lipopolysaccharides). There is evidence that certain cyanobacterial toxins are genotoxic and carcinogenic; however, the mechanisms of their potential carcinogenicity are not well understood. The most frequently occurring and widespread cyanotoxins in brackish and freshwater blooms are the cyclic heptapeptides, i.e., microcystins (MCs), and the pentapeptides, i.e., nodularins (NODs). The main mechanism associated with potential carcinogenic activity of MCs and NOD is the inhibition of protein phosphatases, which leads to the hyperphosphorylation of cellular proteins, which is considered to be associated with their tumor-promoting activity. Apart from this, MCs and NOD induce increased formation of reactive oxygen species and, consequently, oxidative DNA damage. There is also evidence that MCs and NOD induce micronuclei, and NOD was shown to have aneugenic activity. Both cyanotoxins interfere with DNA damage repair pathways, which, along with DNA damage, is an important factor involved in the carcinogenicity of these agents. Furthermore, these toxins increase the expression of TNF-α and early-response genes, including proto-oncogenes, genes involved in the response to DNA damage, cell cycle arrest, and apoptosis. Rodent studies indicate that MCs and NOD are tumor promotors, whereas NOD is thought to have also tumor-initiating activity. Another cyanobacterial toxin, cylindrospermopsin (CYN), which has been neglected for a long time, is lately being increasingly found in the freshwater environment. The principal mechanism of its toxicity is the irreversible inhibition of protein synthesis. It is pro-genotoxic, and metabolic activation by cytochrome P-450 enzymes is needed for its genotoxic activity. In metabolically competent cells, it induces DNA strand breaks and exerts clastogenic and aneugenic activity. In addition, CYN increased the expression of p53 regulated genes involved in cell cycle arrest, DNA damage repair, and apoptosis. It also has cell transforming potential, and limited preliminary rodent studies indicate that CYN could have tumor-initiating activity. In 2010, the International Agency for Research on Cancer (IARC) classified MCLR as possible human carcinogen (Group 2B). Although there is not enough available information for the classification of other cyanobacterial toxins, the existing data from in vitro and in vivo studies indicate that NOD and especially CYN may be even more hazardous than MCLR to human and animal health. In addition in the environment, cyanobacterial toxins occur in complex mixtures as well as together with other anthropogenic contaminants, and numerous studies showed that the toxic/genotoxic potential of the extracts from cyanobacterial scums is higher than that of purified toxins. This means that the mixtures of toxins to which humans are exposed may pose higher health risks than estimated from the toxicological data of a single toxin. Future research efforts should focus on the elucidation of the carcinogenic potential of NOD, CYN, and the mixture of cyanobacterial extracts, as well as on the identification of possible novel toxins. Copyright © 2011 Elsevier B.V. All rights reserved.

Key Characteristics of Carcinogens as a Basis for Organizing Data on Mechanisms of Carcinogenesis

PubMed Central

Smith, Martyn T.; Guyton, Kathryn Z.; Gibbons, Catherine F.; Fritz, Jason M.; Portier, Christopher J.; Rusyn, Ivan; DeMarini, David M.; Caldwell, Jane C.; Kavlock, Robert J.; Lambert, Paul F.; Hecht, Stephen S.; Bucher, John R.; Stewart, Bernard W.; Baan, Robert A.; Cogliano, Vincent J.; Straif, Kurt

2015-01-01

Background: A recent review by the International Agency for Research on Cancer (IARC) updated the assessments of the > 100 agents classified as Group 1, carcinogenic to humans (IARC Monographs Volume 100, parts A–F). This exercise was complicated by the absence of a broadly accepted, systematic method for evaluating mechanistic data to support conclusions regarding human hazard from exposure to carcinogens. Objectives and Methods: IARC therefore convened two workshops in which an international Working Group of experts identified 10 key characteristics, one or more of which are commonly exhibited by established human carcinogens. Discussion: These characteristics provide the basis for an objective approach to identifying and organizing results from pertinent mechanistic studies. The 10 characteristics are the abilities of an agent to 1) act as an electrophile either directly or after metabolic activation; 2) be genotoxic; 3) alter DNA repair or cause genomic instability; 4) induce epigenetic alterations; 5) induce oxidative stress; 6) induce chronic inflammation; 7) be immunosuppressive; 8) modulate receptor-mediated effects; 9) cause immortalization; and 10) alter cell proliferation, cell death, or nutrient supply. Conclusion: We describe the use of the 10 key characteristics to conduct a systematic literature search focused on relevant end points and construct a graphical representation of the identified mechanistic information. Next, we use benzene and polychlorinated biphenyls as examples to illustrate how this approach may work in practice. The approach described is similar in many respects to those currently being implemented by the U.S. EPA’s Integrated Risk Information System Program and the U.S. National Toxicology Program. Citation: Smith MT, Guyton KZ, Gibbons CF, Fritz JM, Portier CJ, Rusyn I, DeMarini DM, Caldwell JC, Kavlock RJ, Lambert P, Hecht SS, Bucher JR, Stewart BW, Baan R, Cogliano VJ, Straif K. 2016. Key characteristics of carcinogens as a basis for organizing data on mechanisms of carcinogenesis. Environ Health Perspect 124:713–721; http://dx.doi.org/10.1289/ehp.1509912 PMID:26600562

Key Characteristics of Carcinogens as a Basis for Organizing Data on Mechanisms of Carcinogenesis.

PubMed

Smith, Martyn T; Guyton, Kathryn Z; Gibbons, Catherine F; Fritz, Jason M; Portier, Christopher J; Rusyn, Ivan; DeMarini, David M; Caldwell, Jane C; Kavlock, Robert J; Lambert, Paul F; Hecht, Stephen S; Bucher, John R; Stewart, Bernard W; Baan, Robert A; Cogliano, Vincent J; Straif, Kurt

2016-06-01

A recent review by the International Agency for Research on Cancer (IARC) updated the assessments of the > 100 agents classified as Group 1, carcinogenic to humans (IARC Monographs Volume 100, parts A-F). This exercise was complicated by the absence of a broadly accepted, systematic method for evaluating mechanistic data to support conclusions regarding human hazard from exposure to carcinogens. IARC therefore convened two workshops in which an international Working Group of experts identified 10 key characteristics, one or more of which are commonly exhibited by established human carcinogens. These characteristics provide the basis for an objective approach to identifying and organizing results from pertinent mechanistic studies. The 10 characteristics are the abilities of an agent to 1) act as an electrophile either directly or after metabolic activation; 2) be genotoxic; 3) alter DNA repair or cause genomic instability; 4) induce epigenetic alterations; 5) induce oxidative stress; 6) induce chronic inflammation; 7) be immunosuppressive; 8) modulate receptor-mediated effects; 9) cause immortalization; and 10) alter cell proliferation, cell death, or nutrient supply. We describe the use of the 10 key characteristics to conduct a systematic literature search focused on relevant end points and construct a graphical representation of the identified mechanistic information. Next, we use benzene and polychlorinated biphenyls as examples to illustrate how this approach may work in practice. The approach described is similar in many respects to those currently being implemented by the U.S. EPA's Integrated Risk Information System Program and the U.S. National Toxicology Program. Smith MT, Guyton KZ, Gibbons CF, Fritz JM, Portier CJ, Rusyn I, DeMarini DM, Caldwell JC, Kavlock RJ, Lambert P, Hecht SS, Bucher JR, Stewart BW, Baan R, Cogliano VJ, Straif K. 2016. Key characteristics of carcinogens as a basis for organizing data on mechanisms of carcinogenesis. Environ Health Perspect 124:713-721; http://dx.doi.org/10.1289/ehp.1509912.

Chlorophyll catalyse the photo-transformation of carcinogenic benzo[a]pyrene in water

PubMed Central

Luo, Lijuan; Lai, Xueying; Chen, Baowei; Lin, Li; Fang, Ling; Tam, Nora F. Y.; Luan, Tiangang

2015-01-01

Algal blooms cause great damage to water quality and aquaculture. However, this study showed that dead algal cells and chlorophyll could accelerate the photo-transformation of benzo[a]pyrene (BaP), a ubiquitous and persistent pollutant with potently mutagenic and carcinogenic toxicities, under visible light irradiation. Chlorophyll was found to be the major active substance in dead algal cells, and generated a high level of singlet oxygen to catalyse the photo-transformation of BaP. According to various BaP metabolites formed, the degradation mechanism was proposed as that chlorophyll in dead algal cells photo-oxidized BaP to quinones via photocatalytic generation of singlet oxygen. The results provided a good insight into the role of chlorophyll in the photo-transformation of organic contaminants and could be a possible remediation strategy of organic pollutants in natural environment. PMID:26239357

Health risk assessment of trace elements via dietary intake of 'non-piscine protein source' foodstuffs (meat, milk and egg) in Bangladesh.

PubMed

Shaheen, Nazma; Ahmed, Md Kawser; Islam, Md Saiful; Habibullah-Al-Mamun, Md; Tukun, Avonti Basak; Islam, Saiful; M A Rahim, Abu Torab

2016-04-01

Concentrations of six trace elements [chromium (Cr), nickel (Ni), copper (Cu), cadmium (Cd), lead (Pb) and arsenic (As)] were assessed in 'non-piscine protein source' foodstuffs (meat, milk and eggs) to evaluate contamination level and human health risks in Bangladesh. The range of Cr, Ni, Cu, Cd, Pb and As in the investigated foodstuffs was 1.24-2.17, 1.29-2.56, 0.92-2.31, 0.12-0.44, 0.15-0.48 and 0.14-0.57 mg kg fresh weight(-1), respectively. The estimated mean levels of most of the elements were higher than the maximum allowable concentration (MAC) for dietary foods. The estimated daily intakes (EDIs) of Cr and Cd were higher than the maximum tolerable daily intake (MTDI) for children, indicating that they are more susceptible to toxic elements through food consumption. The target hazard quotients (THQs) and target carcinogenic risk (TCR) of As (THQ > 1 and TCR > 10(-4)) for both the adults and children suggest that the consumers of non-piscine foodstuffs (especially cow milk and chicken meat) are exposed chronically to metal pollution with carcinogenic and non-carcinogenic health consequences.

Alert-QSAR. Implications for Electrophilic Theory of Chemical Carcinogenesis

PubMed Central

Putz, Mihai V.; Ionaşcu, Cosmin; Putz, Ana-Maria; Ostafe, Vasile

2011-01-01

Given the modeling and predictive abilities of quantitative structure activity relationships (QSARs) for genotoxic carcinogens or mutagens that directly affect DNA, the present research investigates structural alert (SA) intermediate-predicted correlations ASA of electrophilic molecular structures with observed carcinogenic potencies in rats (observed activity, A = Log[1/TD50], i.e., ASA=f(X1SA,X2SA,…)). The present method includes calculation of the recently developed residual correlation of the structural alert models, i.e., ARASA=f(A−ASA,X1SA,X2SA,…). We propose a specific electrophilic ligand-receptor mechanism that combines electronegativity with chemical hardness-associated frontier principles, equality of ligand-reagent electronegativities and ligand maximum chemical hardness for highly diverse toxic molecules against specific receptors in rats. The observed carcinogenic activity is influenced by the induced SA-mutagenic intermediate effect, alongside Hansch indices such as hydrophobicity (LogP), polarizability (POL) and total energy (Etot), which account for molecular membrane diffusion, ionic deformation, and stericity, respectively. A possible QSAR mechanistic interpretation of mutagenicity as the first step in genotoxic carcinogenesis development is discussed using the structural alert chemoinformation and in full accordance with the Organization for Economic Co-operation and Development QSAR guidance principles. PMID:21954348

Evidence supporting product standards for carcinogens in smokeless tobacco products

PubMed Central

Hatsukami, Dorothy K.; Stepanov, Irina; Severson, Herb; Jensen, Joni A.; Lindgren, Bruce R.; Horn, Kimberly; Khariwala, Samir S.; Martin, Julia; Carmella, Steven G.; Murphy, Sharon E.; Hecht, Stephen S.

2014-01-01

Smokeless tobacco (ST) products sold in the U.S. vary significantly in yields of nicotine and tobacco-specific nitrosamines (TSNA). With the passage of the Family Smoking Prevention and Tobacco Control Act, the Food and Drug Administration now has the authority to establish product standards. However, limited data exist determining the relative roles of pattern of ST use versus constituent levels in the ST product in exposure of users to carcinogens. In this study, ST users of brands varying in nicotine and TSNA content were recruited from three different regions in the U.S. Participants underwent two assessment sessions. During these sessions, demographic and ST use history information along with urine samples to assess biomarkers of exposure and effect were collected. During the time between data collection, ST users recorded the amount and duration of ST use on a daily basis using their diary cards. Results showed that independent of pattern of ST use and nicotine yields, levels of TSNA in ST products played a significant role in carcinogen exposure levels. Product standards for reducing levels of TSNA in ST products are necessary to decrease exposure to these toxicants and potentially to reduce risk for cancer. PMID:25524878

Ingested nitrate and nitrite and stomach cancer risk: an updated review.

PubMed

Bryan, Nathan S; Alexander, Dominik D; Coughlin, James R; Milkowski, Andrew L; Boffetta, Paolo

2012-10-01

Nitrite and nitrate are naturally occurring molecules in vegetables and also added to cured and processed meats to delay spoilage and pathogenic bacteria growth. Research over the past 15 years has led to a paradigm change in our ideas about health effects of both nitrite and nitrate. Whereas, historically nitrite and nitrate were considered harmful food additives and listed as probable human carcinogens under conditions where endogenous nitrosation could take place, they are now considered by some as indispensible nutrients essential for cardiovascular health by promoting nitric oxide (NO) production. We provide an update to the literature and knowledge base concerning their safety. Most nitrite and nitrate exposure comes from naturally occurring and endogenous sources and part of the cell signaling effects of NO involve nitrosation. Nitrosation must now be considered broadly in terms of both S- and N-nitrosated species, since S-nitrosation is kinetically favored. Protein S-nitrosation is a significant part of the role of NO in cellular signal transduction and is involved in critical aspects of cardiovascular health. A critical review of the animal toxicology literature of nitrite indicates that in the absence of co-administration of a carcinogenic nitrosamine precursor, there is no evidence for carcinogenesis. Newly published prospective epidemiological cohort studies indicate that there is no association between estimated intake of nitrite and nitrate in the diet and stomach cancer. This new and growing body of evidence calls for a reconsideration of nitrite and nitrate safety. Copyright © 2012 Elsevier Ltd. All rights reserved.

Interaction of Drugs, Biologics, and Chemicals in U.S. Military Forces: Current and Future Issues.

DTIC Science & Technology

1996-12-01

receive the following on entering ac- tive duty: "* poliovirus vaccine, live oral trivalent type 1, 2, and 3; "* measles and rubella virus vaccine live or...selected individuals. Reserve component personnel usually receive oral poliovirus vaccine, diphtheria-tetanus toxoid, and influenza virus vaccines... reproductive toxicity, neurotoxicity, and carcinogenicity). However, to conserve resources and as a starting point, the committee sug- gests the following

The Dangers of Cassava (Tapioca) Consumption

PubMed Central

Hall, Michael J

1987-01-01

Cassava (Tapioca) is a worldwide staple food consumed by over 800 million people. It contains cyanide which may lead to acute toxicity or chronically may be an aetiological factor in tropical nutritional amblyopia, tropical neuropathy, endemic goitre, cretinism and tropical diabetes. It may also have carcinogenic potential. However, despite nutritional limitations it has many advantages as a crop to the subsistence farmer and would be difficult to replace. PMID:28906749

CHARACTERISTICS AND TOXICITY OF THE CHLORINATED DRINKING WATER DISINFECTION BY-PRODUCT 3-CHLORO-4-(DICHLOROMETHYL)-5-HYDROXY-2[5H]-FURANONE (MX) TO MEDAKA (ORYZIAS LATIPES)

EPA Science Inventory

The compound 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone, also know as MX, is a by-product of wood pulp manufacture and a contaminant of chlorinated drinking and sewage water. MX has recently been shown to be a multi-site carcinogen in rodents. We investigated the acute...

Propagation of normal human epithelial cell populations using an in vivo culture system. Description and applications.

PubMed Central

Klein-Szanto, A. J.; Terzaghi, M.; Mirkin, L. D.; Martin, D.; Shiba, M.

1982-01-01

A new model using xenotransplanted human epithelia was developed for the study of toxic and carcinogenic effects of chemicals. Epithelial cells from the respiratory tract of 4 male and 3 female premature and fullterm fetuses were enzymatically removed and inoculated into deepithelialized rat tracheas. These were sealed at both ends and transplanted subcutaneously into nude mice. After 3-4 weeks, a normal mucociliary epithelium covered the tracheal lumen. At this stage the epithelial cells could be isolated again and transplanted into new denuded rat tracheas. This passaging could be repeated up to six times, each permitting an amplification factor of approximately 3. Tracheal transplants containing cells of human origin (in vivo Passages 2-4) were treated with 7,12-dimethylbenz(a)anthracene. Hyperplasias, squamous metaplasias, and dysplasias were seen 1-8 weeks after initiation of treatment, indicating that the responses of human and rodent epithelial cells to polycyclic aromatic hydrocarbons are similar. Initial experiments with skin and esophageal epithelia suggest that other covering epithelia could also be used in this fashion for evaluation of toxicants and carcinogens that are likely to come into contact with these tissues. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:6821529

Hazard assessment of three haloacetic acids, as byproducts of water disinfection, in human urothelial cells.

PubMed

Marsà, Alicia; Cortés, Constanza; Hernández, Alba; Marcos, Ricard

2018-05-15

Disinfection by-products (DBPs) are compounds produced in the raw water disinfection processes. Although increased cancer incidence has been associated with exposure to this complex mixture, the carcinogenic potential of individual DBPs remains not well known; thus, further studies are required. Haloacetic acids (HAAs) constitute an important group among DBPs. In this study, we have assessed the in vitro carcinogenic potential of three HAAs namely chloro-, bromo-, and iodoacetic acids. Using a long-term (8 weeks) and sub-toxic doses exposure scenario, different in vitro transformation markers were evaluated using a human urothelial cell line (T24). Our results indicate that long-term exposure to low doses of HAAs did not reproduce the genotoxic effects observed in acute treatments, where oxidative DNA damage was induced. No changes in the transformation endpoints analyzed were observed, as implied by the absence of significant morphological, cell growth rate and anchorage-independent cell growth pattern modifications. Interestingly, HAA-long-term exposed cells developed resistance to oxidative stress damage, what would explain the observed differences between acute and long-term exposure conditions. Accordingly, data obtained under long-term exposure to sub-toxic doses of HAAs could be more accurate, in terms of risk assessment, than under acute exposure scenarios. Copyright © 2018 Elsevier Inc. All rights reserved.

Biomarkers of Nanoparticles Impact on Biological Systems

NASA Astrophysics Data System (ADS)

Mikhailenko, V.; Ieleiko, L.; Glavin, A.; Sorochinska, J.

Studies of nanoscale mineral fibers have demonstrated that the toxic and carcinogenic effects are related to the surface area and surface activity of inhaled particles. Particle surface characteristics are considered to be key factors in the generation of free radicals and reactive oxygen species and are related to the development of apoptosis or cancer. Existing physico-chemical methods do not always allow estimation of the nanoparticles impact on organismal and cellular levels. The aim of this study was to develop marker system for evaluation the toxic and carcinogenic effects of nanoparticles on cells. The markers are designed with respect to important nanoparticles characteristics for specific and sensitive assessment of their impact on biological system. We have studied DNA damage, the activity of xanthine oxidoreductase influencing the level of free radicals, bioenergetic status, phospholipids profile and formation of 1H-NMR-visible mobile lipid domains in Ehrlich carcinoma cells. The efficiency of the proposed marker system was tested in vivo and in vitro with the use of C60 fullerene nanoparticles and multiwalled carbon nanotubes. Our data suggest that multiwalled carbon nanotubes and fullerene C60 may pose genotoxic effect, change energy metabolism and membrane structure, alter free radical level via xanthine oxidase activation and cause mobile lipid domains formation as determined in vivo and in vitro studies on Ehrlich carcinoma cells.

Multiple resistance to carcinogens and xenobiotics: P-glycoproteins as universal detoxifiers.

PubMed

Efferth, Thomas; Volm, Manfred

2017-07-01

The detoxification of toxic substances is of general relevance in all biological systems. The plethora of exogenous xenobiotic compounds and endogenous toxic metabolic products explains the evolutionary pressure of all organisms to develop molecular mechanisms to detoxify and excrete harmful substances from the body. P-glycoprotein and other members of the ATP-binding cassette (ABC) transporter family extrude innumerous chemical compounds out of cells. Their specific expression in diverse biological contexts cause different phenotypes: (1) multidrug resistance (MDR) and thus failure of cancer chemotherapy, (2) avoidance of accumulation of carcinogens and prevention of carcinogenesis in healthy tissues, (3) absorption, distribution, metabolization and excretion (ADME) of pharmacological drugs in human patients, (4) protection from environmental toxins in aquatic organisms (multi-xenobiotic resistance, MXR). Hence ABC-transporters may have opposing effects for organismic health reaching from harmful in MDR of tumors to beneficial for maintenance of health in MXR. While their inhibition by specific inhibitors may improve treatment success in oncology and avoid carcinogenesis, blocking of ABC-transporter-driven efflux by environmental pollutants leads to ecotoxicological consequences in marine biotopes. Poisoned seafood may enter the food-chain and cause intoxications in human beings. As exemplified with ABC-transporters, joining forces in interdisciplinary research may, therefore, be a wise strategy to fight problems in human medicine and environmental sciences.

Combined ultrasound with Fenton treatment for the degradation of carcinogenic polycyclic aromatic hydrocarbons in textile dying sludge.

PubMed

Zhang, Jian-Hao; Zou, Hai-Yuan; Ning, Xun-An; Lin, Mei-Qing; Chen, Chang-Min; An, Tai-Cheng; Sun, Jian

2017-03-22

To develop an effective method to remove the toxic and carcinogenic polycyclic aromatic hydrocarbons (CPAHs) from textile dyeing sludge, five CPAHs were selected to investigate the degradation efficiencies using ultrasound combined with Fenton process (US/Fenton). The results showed that the synergistic effect of the US/Fenton process on the degradation of CPAHs in textile dyeing sludge was significant with the synergy degree of 30.4. During the US/Fenton process, low ultrasonic density showed significant advantage in degrading the CPAHs in textile dyeing sludge. Key reaction parameters on CPAHs degradation were optimized by the central composite design as followed: H 2 O 2 concentration of 152 mmol/L, ultrasonic density of 408 W/L, pH value of 3.7, the molar ratio of H 2 O 2 to Fe 2+ of 1.3 and reaction time of 43 min. Under the optimal conditions of the US/Fenton process, the degradation efficiencies of five CPAHs were obtained as 81.23% (benzo[a]pyrene) to 84.98% (benz[a]anthracene), and the benzo[a]pyrene equivalent (BaP eq ) concentrations of five CPAHs declined by 81.22-85.19%, which indicated the high potency of US/Fenton process for removing toxic CPAHs from textile dyeing sludge.

Chemical interaction: enhancement and inhibition of clastogenicity.

PubMed Central

Anwar, W A

1993-01-01

Most environmental exposures involve concurrent or sequential exposure to multiple chemicals in air, water, and food. Interactive effects in carcinogenesis have been described for certain combinations of agents. They are described in terms of enhancement or inhibition of carcinogenesis. Enhancement effects have been documented for cigarette smoking in combination with exposure to asbestos, radon, alcohol, or other exposures. A variety of inhibitors of carcinogenesis have also been described. They are classified into agents preventing formation of carcinogens; blocking agents; and suppressing agents. Assessment of risk from exposure to multiple agents can be derived either from epidemiological studies in relation to actual exposure or from laboratory studies after controlled exposure to different agents. Prediction of how toxic components of mixtures will interact should be based on an understanding of the mechanisms of such interactions. Compounds may interact chemically, yielding new toxic components or causing a change in the biological availability of the existing components or metabolites. In humans, great individual variability in response is to be expected because of genetic heterogeneity or acquired host susceptibility factors. Interaction is thus a key component in the risk assessment process. In this paper, the definition of interaction and the theoretical basis for different types of interaction in cancer causation are reviewed. Epidemiological and experimental studies showing interactive effects of two chemical carcinogens are also presented. PMID:8143617

The history, genotoxicity, and carcinogenicity of carbon-based fuels and their emissions. Part 3: diesel and gasoline.

PubMed

Claxton, Larry D

2015-01-01

Within this review the genotoxicity of diesel and gasoline fuels and emissions is placed in an historical context. New technologies have changed the composition of transportation methods considerably, reducing emissions of many of the components of health concern. The similarity of modern diesel and gasoline fuels and emissions to other carbonaceous fuels and emissions is striking. Recently an International Agency for Research on Cancer (IARC) Working Group concluded that there was sufficient evidence in humans for the carcinogenicity of diesel exhaust (Group 1). In addition, the Working Group found that diesel exhaust has "a positive association (limited evidence) with an increased risk of bladder cancer." Like most other carbonaceous fuel emissions, diesel and gasoline exhausts contain toxic levels of respirable particles (PM <2.5μm) and polycyclic aromatic hydrocarbons. However, the level of toxic components in exhausts from diesel and gasoline emissions has declined in certain regions over time because of changes in engine design, the development of better aftertreatment devices (e.g., catalysts), increased fuel economy, changes in the fuels and additives used, and greater regulation. Additional research and better exposure assessments are needed so that decision makers and the public can decide to what extent diesel and gasoline engines should be replaced. Copyright © 2014 Elsevier B.V. All rights reserved.

Systems biology approaches to evaluate arsenic toxicity and carcinogenicity: an overview.

PubMed

Bhattacharjee, Pritha; Chatterjee, Debmita; Singh, Keshav K; Giri, Ashok K

2013-08-01

Long term exposure to arsenic, either through groundwater, food stuff or occupational sources, results in a plethora of dermatological and non-dermatological health effects including multi-organ cancer and early mortality. Several epidemiological studies, across the globe have reported arsenic-induced health effects and cancerous outcomes; but the prevalence of such diseases varies depending on environmental factors (geographical location, exposure level), and genetic makeup (and variants thereof); which is further modulated by several other factors like ethnicity, age-sex, smoking status, diet, etc. It is also interesting to note that, chronic arsenic exposure to a similar extent, even among the same family members, result in wide inter-individual variations. To understand the adverse effect of this toxic metabolite on biological system (cellular targets), and to unravel the underlying molecular basis (at the level of transcript, proteome, or metabolite), a holistic, systems biology approach was taken. Due to the paradoxical nature and unavailability of any suitable animal model system; the literature review is primarily based on cell line and population based studies. Thus, here we present a comprehensive review on the systems biology approaches to explore the underlying mechanism of arsenic-induced carcinogenicity, along with our own observations and an overview of mitigation strategies and their effectiveness till date. Copyright © 2013 Elsevier GmbH. All rights reserved.

Targeting the PI3K/Akt/mTOR pathway: effective combinations and clinical considerations

PubMed Central

LoPiccolo, Jaclyn; Blumenthal, Gideon M.; Bernstein, Wendy B.; Dennis, Phillip A.

2008-01-01

The PI3K/Akt/mTOR pathway is a prototypic survival pathway that is constitutively activated in many types of cancer. Mechanisms for pathway activation include loss of tumor suppressor PTEN function, amplification or mutation of PI3K, amplification or mutation of Akt, activation of growth factor receptors, and exposure to carcinogens. Once activated, signaling through Akt can be propagated to a diverse array of substrates, including mTOR, a key regulator of protein translation. This pathway is an attractive therapeutic target in cancer because it serves as a convergence point for many growth stimuli, and through its downstream substrates, controls cellular processes that contribute to the initiation and maintenance of cancer. Moreover, activation of the Akt/mTOR pathway confers resistance to many types of cancer therapy, and is a poor prognostic factor for many types of cancers. This review will provide an update on the clinical progress of various agents that target the pathway, such as the Akt inhibitors perifosine and PX-866 and mTOR inhibitors (rapamycin, CCI-779, RAD-001) and discuss strategies to combine these pathway inhibitors with conventional chemotherapy, radiotherapy, as well as newer targeted agents. We will also discuss how the complex regulation of the PI3K/Akt/mTOR pathway poses practical issues concerning the design of clinical trials, potential toxicities and criteria for patient selection. PMID:18166498

Agricultural pesticide use in California: pesticide prioritization, use densities, and population distributions for a childhood cancer study.

PubMed Central

Gunier, R B; Harnly, M E; Reynolds, P; Hertz, A; Von Behren, J

2001-01-01

Several studies have suggested an association between childhood cancer and pesticide exposure. California leads the nation in agricultural pesticide use. A mandatory reporting system for all agricultural pesticide use in the state provides information on the active ingredient, amount used, and location. We calculated pesticide use density to quantify agricultural pesticide use in California block groups for a childhood cancer study. Pesticides with similar toxicologic properties (probable carcinogens, possible carcinogens, genotoxic compounds, and developmental or reproductive toxicants) were grouped together for this analysis. To prioritize pesticides, we weighted pesticide use by the carcinogenic and exposure potential of each compound. The top-ranking individual pesticides were propargite, methyl bromide, and trifluralin. We used a geographic information system to calculate pesticide use density in pounds per square mile of total land area for all United States census-block groups in the state. Most block groups (77%) averaged less than 1 pound per square mile of use for 1991-1994 for pesticides classified as probable human carcinogens. However, at the high end of use density (> 90th percentile), there were 493 block groups with more than 569 pounds per square mile. Approximately 170,000 children under 15 years of age were living in these block groups in 1990. The distribution of agricultural pesticide use and number of potentially exposed children suggests that pesticide use density would be of value for a study of childhood cancer. PMID:11689348

Oxidative Stress Mechanisms Do Not Discriminate between Genotoxic and Nongenotoxic Liver Carcinogens.

PubMed

Deferme, Lize; Wolters, Jarno; Claessen, Sandra; Briedé, Jacco; Kleinjans, Jos

2015-08-17

It is widely accepted that in chemical carcinogenesis different modes-of-action exist, e.g., genotoxic (GTX) versus nongenotoxic (NGTX) carcinogenesis. In this context, it has been suggested that oxidative stress response pathways are typical for NGTX carcinogenesis. To evaluate this, we examined oxidative stress-related changes in gene expression, cell cycle distribution, and (oxidative) DNA damage in human hepatoma cells (HepG2) exposed to GTX-, NGTX-, and noncarcinogens, at multiple time points (4-8-24-48-72 h). Two GTX (azathriopine (AZA) and furan) and two NGTX (tetradecanoyl-phorbol-acetate, (TPA) and tetrachloroethylene (TCE)) carcinogens as well as two noncarcinogens (diazinon (DZN, d-mannitol (Dman)) were selected, while per class one compound was deemed to induce oxidative stress and the other not. Oxidative stressors AZA, TPA, and DZN induced a 10-fold higher number of gene expression changes over time compared to those of furan, TCE, or Dman treatment. Genes commonly expressed among AZA, TPA, and DZN were specifically involved in oxidative stress, DNA damage, and immune responses. However, differences in gene expression between GTX and NGTX carcinogens did not correlate to oxidative stress or DNA damage but could instead be assigned to compound-specific characteristics. This conclusion was underlined by results from functional readouts on ROS formation and (oxidative) DNA damage. Therefore, oxidative stress may represent the underlying cause for increased risk of liver toxicity and even carcinogenesis; however, it does not discriminate between GTX and NGTX carcinogens.

Assessment of the mode of action underlying development of forestomach tumors in rodents following oral exposure to ethyl acrylate and relevance to humans.

PubMed

Thompson, Chad M; Suh, Mina; Chappell, Grace; Borghoff, Susan; Ellis-Hutchings, Robert; Wiench, Karin; Finch, Lavorgie; Proctor, Deborah M

2018-05-05

Chronic repeated gavage dosing of high concentrations of ethyl acrylate (EA) causes forestomach tumors in rats and mice. For two decades, there has been general consensus that these tumors are unique to rodents because of: i) lack of carcinogenicity in other organs, ii) specificity to the forestomach (an organ unique to rodents which humans do not possess), iii) lack of carcinogenicity by other routes of exposure, and iv) obvious site of contact toxicity at carcinogenic doses. In 1986, EA was classified as possibly carcinogenic to humans by the International Agency for Research on Cancer (IARC). However, by applying a MOA analyses and human relevance framework assessment, the weight-of-evidence supports a cytotoxic MOA with the following key events: i) bolus delivery of EA to forestomach lumen and subsequent absorption, ii) cytotoxicity likely due to saturation of enzymatic detoxification, iii) chronic regenerative hyperplasia, and iv) spontaneous mutation due to increased cell replication and cell population. Clonal expansion of initiated cells thus results in late onset tumorigenesis. The key events in this 'wound and healing' MOA provide high confidence in the MOA as assessed by evolved Bradford-Hill Criteria. The weight-of-evidence supported by the proposed MOA, combined with a unique tissue that does not exist in humans, indicates that EA is highly unlikely to pose a human cancer hazard. Copyright © 2018. Published by Elsevier Inc.

Opportunities to integrate new approaches in genetic toxicology: an ILSI-HESI workshop report.

PubMed

Zeiger, Errol; Gollapudi, Bhaskar; Aardema, Marilyn J; Auerbach, Scott; Boverhof, Darrell; Custer, Laura; Dedon, Peter; Honma, Masamitsu; Ishida, Seiichi; Kasinski, Andrea L; Kim, James H; Manjanatha, Mugimane G; Marlowe, Jennifer; Pfuhler, Stefan; Pogribny, Igor; Slikker, William; Stankowski, Leon F; Tanir, Jennifer Y; Tice, Raymond; van Benthem, Jan; White, Paul; Witt, Kristine L; Thybaud, Véronique

2015-04-01

Genetic toxicity tests currently used to identify and characterize potential human mutagens and carcinogens rely on measurements of primary DNA damage, gene mutation, and chromosome damage in vitro and in rodents. The International Life Sciences Institute Health and Environmental Sciences Institute (ILSI-HESI) Committee on the Relevance and Follow-up of Positive Results in In Vitro Genetic Toxicity Testing held an April 2012 Workshop in Washington, DC, to consider the impact of new understanding of biology and new technologies on the identification and characterization of genotoxic substances, and to identify new approaches to inform more accurate human risk assessment for genetic and carcinogenic effects. Workshop organizers and speakers were from industry, academe, and government. The Workshop focused on biological effects and technologies that would potentially yield the most useful information for evaluating human risk of genetic damage. Also addressed was the impact that improved understanding of biology and availability of new techniques might have on genetic toxicology practices. Workshop topics included (1) alternative experimental models to improve genetic toxicity testing, (2) Biomarkers of epigenetic changes and their applicability to genetic toxicology, and (3) new technologies and approaches. The ability of these new tests and technologies to be developed into tests to identify and characterize genotoxic agents; to serve as a bridge between in vitro and in vivo rodent, or preferably human, data; or to be used to provide dose response information for quantitative risk assessment was also addressed. A summary of the workshop and links to the scientific presentations are provided. © 2014 Wiley Periodicals, Inc.

Cadmium and Cadmium/Zinc Ratios and Tobacco-Related Morbidities

PubMed Central

Richter, Patricia; Faroon, Obaid; Pappas, R. Steven

2017-01-01

Metals are one of five major categories of carcinogenic or toxic constituents in tobacco and tobacco smoke. Cadmium is highly volatile and a higher percentage of the total tobacco cadmium content is efficiently transferred to mainstream tobacco smoke than many other toxic metals in tobacco. Inhaled cadmium bioaccumulates in the lungs and is distributed beyond the lungs to other tissues, with a total body biological half-life of one to two decades. Chronic cadmium exposure through tobacco use elevates blood and urine cadmium concentrations. Cadmium is a carcinogen, and an inducer of proinflammatory immune responses. Elevated exposure to cadmium is associated with reduced pulmonary function, obstructive lung disease, bronchogenic carcinoma, cardiovascular diseases including myocardial infarction, peripheral arterial disease, prostate cancer, cervical cancer, pancreatic cancer, and various oral pathologies. Cadmium and zinc have a toxicologically inverse relationship. Zinc is an essential element and is reportedly antagonistic to some manifestations of cadmium toxicity. This review summarizes associations between blood, urine, and tissue cadmium concentrations with emphasis on cadmium exposure due to tobacco use and several disease states. Available data about zinc and cadmium/zinc ratios and tobacco-related diseases is summarized from studies reporting smoking status. Collectively, data suggest that blood, urine, and tissue cadmium and cadmium/zinc ratios are often significantly different between smokers and nonsmokers and they are also different in smokers for several diseases and cancers. Additional biomonitoring data such as blood or serum and urine zinc and cadmium levels and cadmium/zinc ratios in smokers may provide further insight into the development and progression of diseases of the lung, cardiovascular system, and possibly other organs. PMID:28961214

Cadmium and Cadmium/Zinc Ratios and Tobacco-Related Morbidities.

PubMed

Richter, Patricia; Faroon, Obaid; Pappas, R Steven

2017-09-29

Metals are one of five major categories of carcinogenic or toxic constituents in tobacco and tobacco smoke. Cadmium is highly volatile and a higher percentage of the total tobacco cadmium content is efficiently transferred to mainstream tobacco smoke than many other toxic metals in tobacco. Inhaled cadmium bioaccumulates in the lungs and is distributed beyond the lungs to other tissues, with a total body biological half-life of one to two decades. Chronic cadmium exposure through tobacco use elevates blood and urine cadmium concentrations. Cadmium is a carcinogen, and an inducer of proinflammatory immune responses. Elevated exposure to cadmium is associated with reduced pulmonary function, obstructive lung disease, bronchogenic carcinoma, cardiovascular diseases including myocardial infarction, peripheral arterial disease, prostate cancer, cervical cancer, pancreatic cancer, and various oral pathologies. Cadmium and zinc have a toxicologically inverse relationship. Zinc is an essential element and is reportedly antagonistic to some manifestations of cadmium toxicity. This review summarizes associations between blood, urine, and tissue cadmium concentrations with emphasis on cadmium exposure due to tobacco use and several disease states. Available data about zinc and cadmium/zinc ratios and tobacco-related diseases is summarized from studies reporting smoking status. Collectively, data suggest that blood, urine, and tissue cadmium and cadmium/zinc ratios are often significantly different between smokers and nonsmokers and they are also different in smokers for several diseases and cancers. Additional biomonitoring data such as blood or serum and urine zinc and cadmium levels and cadmium/zinc ratios in smokers may provide further insight into the development and progression of diseases of the lung, cardiovascular system, and possibly other organs.

Heavy metal content and potential health risk of geophagic white clay from the Kumasi Metropolis in Ghana.

PubMed

Nkansah, Marian Asantewah; Korankye, Mavis; Darko, Godfred; Dodd, Matt

2016-01-01

Geophagia is the craving for non-food substances and commonly practiced among pregnant women and children. Consumption of geophagic clay samples can have serious implications on the health of the consumers as a result of the presence of toxic metals such as Pb, As, Hg and Cd. This study sought to determine the levels of heavy metals in the studied geophagic clay samples and to determine the potential risks of heavy metals as cumulative carcinogenic and non-carcinogenic risks to the health of the consumers via oral (ingestion) and dermal exposure routes. A total of thirty (30) white clay samples were analysed using Niton Thermo scientific XRF Analyser (Mobile Test S, NDTr-XL3t-86956, com 24). The clay samples were found to contain essential elements such as Ca, Fe, K and Zn as well as toxic metals such as As and Pb. There were isolated cases of the presence of Hg and all samples had Cd levels below detection. Health risk indices such as hazard quotient and cancer risk were calculated and the results indicated that consumers are likely to suffer from cancer through ingestion of geophagic clay. Bioaccessibility studies were done on zinc and it did not indicate any potential toxicity due to zincs essential nature. The levels of heavy metals in some of the geophagic clay consumed by some residents in the Kumasi were high compared to the Permitted Maximum Tolerable Daily Intake (PMTDI) by (WHO/FAO) and may pose potential health threat over time.

Siderophores, the answer for micro to nanosized asbestos fibre related health hazard

NASA Astrophysics Data System (ADS)

Bhattacharya, Shabori; Ledwani, Lalita; John, P. J.

2016-04-01

Recent studies on the potential toxicity of High Aspect Ratio Nanoparticles (HARN) has yet once again reinforced the health hazard imposed by asbestos fibres ranging from nano to micro size. Asbestos a naturally occurring fibrous mineral declared a Group I definite carcinogen by IARC (International Agency for Research on Cancer), a unit of WHO in the year 1987, has been extensively used since World War II to the near past for various commercial products. According to the most recent World Health Organization (WHO) estimates, asbestos-related diseases, resulting from exposure at workplace claims more than 107000 lives every year worldwide. The various types of toxic effects induced by asbestos in humans include - i) inflammation and fibrogenesis of lung, ii) mesothelioma iii) asbestosis and iv) bronchogenic carcinoma. The stability of asbestos in natural environment and its biological aggressiveness is related to their fibrous structure and dimensions. The actual risk associated with the exposure to nanosized asbestos, which is still unknown and escapes most regulations worldwide, has been shown in various toxicity assessment studies conducted on various animal models.In an effort to reduce the size of asbestos and therby its toxicity by limiting its biopersistence, oxalic acid treatment of asbestos coupled to power ultrasound treatment was carried out. The nanosized particles formed were still found to retain their hazardous effect. Similar were the results obtained on strong acid treatment of asbestos as well. A probable solution to the asbestos toxicity problem therefore envisaged was bioremediation. This involved the secretion of iron chelating molecules termed siderophores by microbes, which are of significance due to their ability to form very stable and soluble complexes with iron. Iron in asbestos composition is a major factor responsible for its carcinogenicity, removal or extraction of which would prove to be an effective answer to the worldwide problem. Siderophores are low molecular weight organic compounds with a very high and specific affinity to chelate iron and enhance their diffusion to the microbial cell surface. A number of successful experiments carried out in vitro have shown positive results concerning reduction in asbestos toxicity on chelation of iron by siderophores. The present investigation tends to put forth the aspect of these biomolecules secreted by specific bacteria and fungi as potent tools to fight the micro to nano sized asbestos fibre toxicity.

A 21st Century Update on Neurotoxicity Risk Assessment

EPA Science Inventory

In 1998, EPA published Guidelines for Neurotoxicity Risk Assessment as the basis for interpreting neurotoxicity results. At that time, the focus was on traditional toxicity testing and human clinical /epidemiological data. More recently, a change in approach to toxicity testing ...

A review on cylindrospermopsin: the global occurrence, detection, toxicity and degradation of a potent cyanotoxin

USGS Publications Warehouse

de la Cruz, Armah A.; Hiskia, Anastasia; Kaloudis, Triantafyllos; Chernoff, Neil; Hill, Donna; Antoniou, Maria G.; He, Xuexiang; Loftin, Keith; O'Shea, Kevin; Zhao, Cen; Pelaez, Miguel; Han, Changseok; Lynch, Trevor J.; Dionysiou, Dionysios D.

2013-01-01

Cylindrospermopsin is an important cyanobacterial toxin found in water bodies worldwide. The ever-increasing and global occurrence of massive and prolonged blooms of cylindrospermopsin-producing cyanobacteria poses a potential threat to both human and ecosystem health. Its toxicity is associated with metabolic activation and may involve mechanisms that adversely affect a wide variety of targets in an organism. Cylindrospermopsin has been shown to be cytotoxic, dermatotoxic, genotoxic, hepatotoxic in vivo, developmentally toxic, and may be carcinogenic. Human exposure may occur through drinking water, during recreational activities and by consuming foods in which the toxin may have bioaccumulated. Drinking water shortages of sufficient quality coupled with growing human pressures and climate variability and change necessitate an integrated and sustainable water management program. This review presents an overview of the importance of cylindrospermopsin, its detection, toxicity, worldwide distribution, and lastly, its chemical and biological degradation and removal by natural processes and drinking water treatment processes.

The impact of tobacco additives on cigarette smoke toxicity: a critical appraisal of tobacco industry studies.

PubMed

Paumgartten, Francisco José Roma; Gomes-Carneiro, Maria Regina; Oliveira, Ana Cecilia Amado Xavier de

2017-09-21

Cigarette production involves a number of substances and materials other than just tobacco, paper and a filter. Tobacco additives include flavorings, enhancers, humectants, sugars, and ammonium compounds. Although companies maintain that tobacco additives do not enhance smoke toxicity and do not make cigarettes more attractive or addictive, these claims are questioned by independent researchers. This study reviewed the studies on the effects of tobacco additives on smoke chemistry and toxicity. Tobacco additives lead to higher levels of formaldehyde and minor changes in other smoke analytes. Toxicological studies (bacterial mutagenicity and mammalian cytoxicity tests, rat 90 days inhalation studies and bone-marrow cell micronucleus assays) found that tobacco additives did not enhance smoke toxicity. Rodent assays, however, poorly predicted carcinogenicity of tobacco smoke, and were clearly underpowered to disclose small albeit toxicologically relevant differences between test (with tobacco additives) and control (without tobacco additives) cigarettes. This literature review led to the conclusion that the impact of tobacco additives on tobacco smoke harmfulness remains unclear.

Cancer risks in naval divers with multiple exposures to carcinogens.

PubMed Central

Richter, Elihu D; Friedman, Lee S; Tamir, Yuval; Berman, Tamar; Levy, Or; Westin, Jerome B; Peretz, Tamar

2003-01-01

We investigated risks for cancer and the case for a cause-effect relationship in five successive cohorts of naval commando divers (n = 682) with prolonged underwater exposures (skin, gastrointestinal tract, and airways) to many toxic compounds in the Kishon River, Israel's most polluted waterway, from 1948 to 1995. Releases of industrial, ship, and agricultural effluents in the river increased substantially, fish yields decreased, and toxic damage to marine organisms increased. Among the divers (16,343 person-years follow-up from 18 years of age to year 2000), the observed/expected ratio for all tumors was 2.29 (p<0.01). Risks increased in cohorts first diving after 1960 compared to risks in earlier cohorts, notably for hematolymphopoietic, central nervous system, gastrointestinal, and skin cancer; induction periods were often brief. The findings suggest that the increases in risk for cancer and short induction periods resulted from direct contact with and absorption of multiple toxic compounds. Early toxic effects in marine life predicted later risks for cancer in divers. PMID:12676624

The toxic Doppelganger: on the ionic and molecular mimicry of cadmium.

PubMed

Chmielowska-Bąk, Jagna; Izbiańska, Karolina; Deckert, Joanna

2013-01-01

Cadmium is a toxic heavy metal which can cause numerous alterations in cell functioning. Exposure to cadmium leads to generation of reactive oxygen species, disorders in membrane structure and functioning, inhibition of respiration, disturbances in ion homeostasis, perturbations in cell division, and initiation of apoptosis and necrosis. This heavy metal is considered a carcinogen by the Agency for Toxic Substances and Disease Registry. At least some of the described toxic effects could result from the ability of cadmium to mimic other divalent ions and alert signal transduction networks. This review describes the role of cadmium mimicry in its uptake, reactive oxygen species generation, alterations in calmodulin, Wnt/β-catenin and estrogen signaling pathways, and modulation of neurotransmission. The last section is dedicated to the single known case of a favorable function performed by cadmium mimicry: marine diatoms, which live in zinc deficient conditions, utilize cadmium as a cofactor in carbonic anhydrase - so far the only described cadmium enzyme.

Toxicity of plant extracts containing pyrrolizidine alkaloids using alternative invertebrate models.

PubMed

Seremet, Oana Cristina; Olaru, Octavian Tudorel; Gutu, Claudia Maria; Nitulescu, George Mihai; Ilie, Mihaela; Negres, Simona; Zbarcea, Cristina Elena; Purdel, Carmen Nicoleta; Spandidos, Demetrios A; Tsatsakis, Aristides M; Coleman, Michael D; Margina, Denisa Marilena

2018-06-01

Pyrrolizidine alkaloids (PAs) are a widespread class of hepatotoxic heterocyclic organic compounds found in approximately 3% of world flora. Some PAs have been shown to have genotoxic and carcinogenic effects. The present study focuses on the toxicity effects of four dry extracts obtained from medicinal plants (Senecio vernalis, Symphytum officinale, Petasites hybridus and Tussilago farfara), on two aquatic organisms, Artemia salina and Daphnia magna, and the correlation with their PAs content. A new GC‑MS method, using a retention time (TR)‑5MS type capillary column was developed. PAs Kovats retention indices, for this type of column were computed for the first time. The lethal dose 50% (LC50) values for the two invertebrate models were correlated (Pearson 's coefficient, >0.9) and the toxicity was PA concentration-dependent, for three of the four extracts. All tested extracts were found to be toxic in both aquatic organism models. The results can be used to develop a GC‑MS validated method for the assay of PAs in medicinal plants with a further potential application in the risk assessment study of PAs toxicity in humans.