This test measures structural chromosomal aberrations (both chromosome- and chromatid-type) in dividing spermatogonial germ cells and is, therefore, expected to be predictive of induction of heritable mutations in these germ cells. The purpose of the in vivo mammalian spermatogonial chromosomal aberration test is to identify those chemicals that cause structural chromosomal aberrations in mammalian spermatogonial cells (1) (2) (3). In addition, this test is relevant to assessing genetoxicity because, although they may vary among species, factors of in vivo metabolism, pharmacokinetics and DNA-repair processes are active and contribute to the response. The original Test Guideline 483 was adopted in 1997. This modified version of the Test Guideline reflects many years of experience with this assay and the potential for integrating or combining this test with other toxicity or genotoxicity studies.
311 chemicals were tested under code, for mutagenicity, in Salmonella typhimurium; 35 of the chemicals were tested more than once in the same or different laboratories. The tests were conducted using a preincubation protocol in the absence of exogenous metabolic activation, and in the presence of liver S-9 from Aroclor-induced male Sprague-Dawley rats and Syrian hamsters. Some of the volatile chemicals were also tested in desiccators. A total of 120 chemicals were mutagenic or weakly mutagenic, 3 were judged questionable, and 172 were non-mutagenic. The remaining 16 chemicals produced different responses in the two or three laboratories in which they were tested. The results and data from these tests are presented.
A urine mutagenicity test for assaying airborne exposure was examined. Airborne particles were collected on glass fiber filters with a high volume sampler 10 meters (m) above the ground. Diesel emission particles were obtained from the exhaust pipe of a diesel truck; coal (8002059) dust was taken from a bituminous coal mine. Urine samples collected from nonsmokers were pooled and divided into seve
BioAssay record AID 399992 submitted by ChEMBL: Mutagenic activity in Salmonella TA 98 by microsome assay in presence of rat liver S9 fraction.
Large-scale initiatives, such as ToxCast, promote a shift in the paradigm for regulatory evaluations of new and existing substances; specifically, away from time-consuming in vivo assays towards predictive, short-term in vitro assays. Unfortunately, the assays included in such initiatives are ill-equipped to assess chemically-induced genetic damage and mutation. Moreover, many currently used mammalian cell genotoxicity assays generate an unacceptably high frequency of false or irrelevant positive results with respect to in vivo mutagenicity and/or carcinogenicity. A novel in vitro gene mutation assay utilizing primary hepatocytes from the transgenic Muta™Mouse was been developed to address the shortfalls of existing in vitro mutagenicity assays. In order to assess the utility of the Muta™Mouse primary hepatocyte assay, the cells were extensively characterized. Freshly isolated cells were found to have a hepatocyte-like morphology, with a large proportion of binucleated cells. After 24 hours ...
Target CAS no. 68391-31-1 - Basic yellow 57 : Summary Genetic toxicity in vitro In a weight of evidence study (Prediction report - Sustainability Support Services (Europe) AB, 2016): 1) The mutagenicity of Basic yellow 57 is estimated using QSAR toolbox 3.3.The substance Basic yellow 57 is estimated to be non-mutagenic in S. typhimurium TA 1535 in the presence of Rat liver S9 metabolic activation in a bacterial reverse mutation assay. 2) The mutagenicity of Basic yellow 57 is estimated using QSAR toolbox 3.3.The substance Basic yellow 57 is estimated to be non-mutagenic in S. typhimurium TA 1538 in the absence of Rat liver S9 metabolic activation in a bacterial reverse mutation assay. In a weight of evidence study (SCCS report, 2009): · Bacterial gene mutation assay was performedby the plate incorporation and pre-incubation method usingSalmonella typhimuriumstrainTA98, TA100, TA102, TA1535 and TA1537.DMSO solution was used as a vehicle. Test chemical conc. used were 3.16, 10, 31.6, 100, 316 and ...
The mutagenic potential of SEX and TAX was assessed by using the Ames Salmonella/Mammalian Microsome Mutagenicity Assay. Tester strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538 were exposed to doses ranging from 1 mg/plate to 10-5 mg/plate. Negative mutagenic responses were observed for both test compounds.*Explosives
In a reverse gene mutation assay in bacteria, performed according to Guideline OECD 471 and in compliance with GLP, histidine-dependent auxotrophic mutants of Salmonella typhimurium, strains TA1535, TA1537, TA98 and TA100, and a tryptophan-dependent mutant ofEscherichia coli, strain WP2uvrA (pKM101), were exposed to the test item diluted in DMSO at the concentrations below. First Test (Plate incorporation method): 5, 15, 50, 150, 500, 1500 and 5000 μg/plate in TA 1535, TA 1537, TA 98, TA 100, and WP2 uvrA (pKM101), with and without S9-mix Second Test (Pre-incubation method): 5, 15, 50, 150, 500, 1500 and 5000 μg/plate in TA 1535, TA 1537, TA 98, TA 100, and WP2 uvrA (pKM101), with and without S9-mix Additional Second Test (Pre-incubation method): 0.15, 0.5, 1.5, 5, 15, 50 and 150 μg/plate in TA 98, TA 100 and TA 1535 strains, without S9-mix 0.5, 1.5, 5, 15, 50, 150 and 500 μg/plate in TA 1537 and WP2 uvrA (pKM101) strains, without S9-mix 0.5, 1.5, 5, 15, 50, 150 and 500 μg/plate in TA 100 ...
1 Vial Semisolid TA100 1 Vial Semisolid TA98 1 Vial Semisolid TA1535 1 Vial Semisolid TA1537 1 Vial Ampicillin Growth Media, Exposure Media and Indicator Media Aroclor 1254 Induced Lyophilized Rat Liver S9 Positive Controls: 2-NF, 2-AA, 9-AA, 4-NQO, N4-ACT. All media and strains provided are sufficient to analyze at least 1 compound, triplicates, 6 concentrations, negative and positive controls, +/- S9. The Ames MPF 98/100/1535/1537 assay comprises the histidine auxotrophic Salmonella tester strains and TA98 and TA1537 for detecting frameshift mutations, as well as TA100 and TA1535 which are reverted by base-pair substitutions and all media required to perform the assay. These kits are shipped at ambient temperature. Strains must be stored at -70°C upon arrival.
Studies were chosen as key when the available study was of relevance and of sufficient quality for classification, labelling and for risk assessment. A key bacterial mutagenicity study according to OECD TG 471 and GLP is available for the registered substance. No evidence for a test-substance related increase in the number of revertants was observed when tested up to cytotoxic concentration in any of the Salmonella typhimurium strains (TA 1535, TA1537, TA98 and TA100) in two independent experiments without and with metabolic activation. Appropriate positive and solvent controls were included and gave expected results. Under the conditions of this study, the registered substance was concluded to be non-mutagenic in the strains tested (Hüls AG, 1996). No data are available for mutagenicity to a bacterial strain capable of detecting cross-linking or oxidising mutagens. In view of the lack of genetic toxicity demonstrated in studies on mammalian cells, and the absence of structural features that ...
10 Vials Semisolid TA100 10 Vials Semisolid TA98 10 Vials Semisolid TA1535 10 Vials Semisolid TA1537 10 Vials Ampicillin Growth Media, Exposure Media and Indicator Media. All media and strains provided are sufficient to analyze at least 10 compounds, triplicates, 6 concentrations, negative and positive controls, +/- S9. The Ames MPF 98/100/1535/1537 assay comprises the histidine auxotrophic Salmonella tester strains and TA98 and TA1537 for detecting frameshift mutations, as well as TA100 and TA1535 which are reverted by base-pair substitutions and all media required to perform the assay. These kits are shipped at ambient temperature. Strains must be stored at -70°C upon arrival.
Allard P, Kleinstreuer NC, Knudsen TB, Colaiacovo MP. 2013. A C. elegans screening platform for the rapid assessment of chemical disruption of germline function. Environ Health Perspect 121:717-724. Leland S, Nagarajan P, Polyzos A, Thomas S, Samaan G, Donnell R, Marchetti F, Venkatachalam S. 2009. Heterozygosity for a Bub1 mutation causes female-specific germ cell aneuploidy in mice. Proc Natl Acad Sci USA 106:12776-12781. Mailhes JB, Yuan ZP. 1987a. Cytogenetic technique for mouse metaphase II oocytes. Gamete Res 18:77-83. OECD (1997), Test No. 473: In vitro Mammalian Chromosome Aberration Test, OECD Guidelines for the Testing of Chemicals, Section 4, OECD Publishing, Paris. DOI: http://dx.doi.org/10.1787/9789264071261-en OECD (1997), Test No. 474: Mammalian Erythrocyte Micronucleus Test, OECD Guidelines for the Testing of Chemicals, Section 4, OECD Publishing, Paris. DOI: http://dx.doi.org/10.1787/9789264071285-en OECD (2014), Test No. 475: Mammalian Bone Marrow Chromosomal Aberration Test, ...
margolin: Margolin et al. (1981) present data from an Ames Salmonella assay, where y is the number of revertant colonies observed on a plate given a dose y of quinoline. The data were subsequently analysed by Breslow (1984), Lawless (1987) and Saha and Paul (2005).
Aurigon is a research institute dedicated to preclinical services for human and veterinary pharmaceuticals, food and chemicals. It provides a full range of advisory and experimental services in pharmacology, bio-/analytics and toxicology.
Citation: Zeiger, E., Anderson, B., Haworth, S., Lawlor, T., and Mortelman, K. Salmonella Mutagenicity Tests V. Results from the Testing of 311 Chemicals Environ. Molec. Mutagen. Vol. 19 (Suppl 21) (1992) 2- ...
Citation: Zeiger, E., Anderson, B., Haworth, S., Lawlor, T., and Mortelman, K. Salmonella Mutagenicity Tests V. Results from the Testing of 311 Chemicals Environ. Molec. Mutagen. Vol. 19 (Suppl 21) (1992) 2- ...
Zhou H., Josephy P.D., Kim D., Guengerich F.P.. Human cytochrome P450 1A2 catalyzes important reactions in xenobiotic metabolism, including the N-hydroxylation of carcinogenic aromatic amines. In 2001, Chevalier et al. reported four new P450 1A2 sequence variants in the human population. We have now expressed these variants in Escherichia coli and measured protein expression (optical spectroscopy of holoenzyme and immunoblotting) and bioactivation of IQ (2-amino-3-methylimidazo[4,5-f]quinoline) and MeIQ (2-amino-2,4-dimethylimidazo[4,5-f]quinoline) in the lacZ reversion mutagenicity test. Enzyme kinetic analyses were performed for N-hydroxylation of five heterocyclic amine substrates and for O-deethylation of phenacetin. The most drastic effect was that of the R431W substitution: no holoenzyme was detectable. This residue is located in the "meander" peptide region and earlier site-directed mutagenesis studies demonstrated that it is critical for maintenance of protein tertiary structure. The ...
7;8-Dihydro-7;8-dihydroxybenzo(a)pyrene 9;10-oxide/chemistry/metabolism/toxicity, Alkylating Agents/chemistry/metabolism/toxicity, Animals, Biological Assay, CHO Cells, Carcinogens/chemistry/metabolism/*toxicity, Cell Line, Cricetinae, DNA Adducts, DNA Repair, Environmental Pollutants/metabolism/*toxicity, Ethyl Methanesulfonate/chemistry/metabolism/toxicity, Humans, Hydrogen Peroxide/metabolism/toxicity, Male, Mitomycin/chemistry/metabolism/toxicity, Molecular Structure, Mutagenicity Tests, Mutagens/chemistry/metabolism/*toxicity, Oxidants/metabolism/toxicity ...
A cell culturelinks test for assessing a drug candidates genetic toxicity has been developed. It may be cheaper than existing animal tests and would allow genetic toxicity tests to be examined far earlier in the drug development process.. Like the current FDA-approved test, the new test looks for DNA damage in red blood cells formed in the bone marrow of mice. The precursors to red blood cells are handy for this because such cells normally lose their nucleus during the last stage of red cell formation, and DNA-damaged precursors generate red blood cells containing an easily detected "micronucleus" consisting of fragments of nuclear DNA.. Unlike the current procedure, which injects the compound into a live mouse, the new assay is a cell-culture system that could allow hundreds or thousands of tests to be performed from the bone marrow of a single mouse, and potentially from human bone marrow.. ...
Biotoxicity, toxicity, ames test, ames testing, genotoxicity test, genotoxicity testing, ta100, ta98, Ames Express, sos chromotest, umu-c assay
Gentronix is pleased to announce the introduction of its new early genotoxicity screening assay BlueScreen HC. BlueScreen HC is a human cell-based reporter assay that monitors expression of the GADD45a gene, a P53 target that is up-regulated in response to all types of genotoxic stress. To coincide with the expansion of cell-based screening services, Gentronix has also announced the introduction of its in vitro Comet assay service.
Session Chairs: Mark W. Powley, US Food and Drug Administration, CDER, Silver Spring, MD; and Leon F. Stankowski Jr., Charles River, Skokie, IL. Genetic toxicology is a critical component of the drug safety assessment process. The overall goal of genetic toxicology testing is to identify test articles capable of damaging DNA as these compounds may also possess carcinogenic properties. Per ICH S2(R1), regulatory testing utilizes a battery approach focusing on gene mutations, structural chromosomal damage (clastogenicity), and numerical chromosomal damage (aneugenicity). Positive results from any of the initial studies may result in additional testing to further define genotoxic risk. Ultimately, genetic toxicology data is integrated into the risk:benefit analysis and may significantly impact regulatory decisions.. This course will provide attendees with a working knowledge of regulatory genetic toxicology. Topics will include reviews of regulatory studies, ICH guidelines (e.g., M3, M7, and S2), ...
Im not sure what is meant by snippet (see Dr. Curls posting below). What I posted to the list was a press release from the Lymphoma Foundation in its entirety. Here again is the posting I made in full provided at bottom of this message. Also, the email did not mentioned mutagenicity. I said if a chemical causes cancer in animals, it is a good bet that humans are also at risk. This has nothing to do with the Ames assay which assesses some types of mutagenicity. I did not say that if a chemical causes a positive response in the Ames assay, it is a risk for people. Thats another issue. Conflating ames - type mutagenicity with cancer induction fails to address the issue at hand. ...
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This non-interventional study will compare the Cobas BRAF V600 mutation assay with in-house methods used in molecular laboratories for the assessment of
Got to watch not to have too much Oranges or Lemon in the hot summer. It can cause skin problems because they contain limonine and that can make it so your skin damages in the sunlight. Great for the winter or if you dont go out much. But if you like doing stuff outside in the summer, it is not wise to drink more than say six ounces of OJ per day if you do it on a daily basis. No problem if you are in an office all day and wear sunscreen when outside or try to stay out of the sun. The thing is, in the summer, you need less food, gaining some energy from the sun. so you may need less vitamin C too since you are processing less food ...
I am taking action for the safety of our country, with the violence, thats going on in our country with GUNS, why do we. Join the campaign and make a difference.
It was the first time HCS Pharma participate at 35th symposium of the French society of genetic toxicology (SFTG) as a sponsor. The implication of the SFTG in the study and assessment of environmental genotoxic agents motive us to be a sponsor of this 35th event.. This year, topic focused on the trans generational genotoxic and epigenetic effects of environmental compounds. Two high level plenary session, presented by Francelyne Marano and Giacomo Cavalli from CNRS, has introduced clearly the different implications of trans generational genotoxicity and epigenetic effects. The role of germinal cells was clearly established in exposition to genotoxic compounds and we were pleased to see clinicians and lab scientists exchanged about this topic.. ...
Quantifying DNA damage is mandatory to assess (i) potential adverse effects of candidate drugs, molecules or extracts developed in the dermo-cosmetic industry, and (ii) the efficacy of anticancer therapies, in order to induce tumor cell genotoxicity. Genotoxic potential effect can be analyzed by different assays, like
Save the date! This years IGG Annual Meeting will be held from the 19th - 20th June 2019 at the Deansgate Hilton in Manchester. This meeting is sponsored by Gentronix and will be on the theme "Regulatory Genetic Toxicology: Theory and Reality". The meeting will start on the evening of the 19th with a keynote from David Kirkland on "Regulatory Assessment of Genotoxicity Data: Past, Present and Future" followed by drinks and bowl food, an excellent opportunity for networking and catching up with colleagues. The 20th will have half a day on "Regulatory Genetic Toxicology: Theory" covering new challenges including oligos and medical devices, while the afternoon will be interactive workshops on proof of exposure and when negative is equivocal. Download the Meeting Flyer for more information. There will be travel bursaries available as well as early bird registration fees and reduced rates for members of EEMGS and affiliated societies. Registration will open soon, so for now, Save the Date!. ...
Often, subject matter experts are available with the knowledge to prevent further damage, yet are unable to get close enough to complete their mission - be it from nuclear contamination, intense pressure, structural instability, or many other threats to human safety. Our best robotic tools are helping, but they are not yet robust enough to function in all environments and perform the basic tasks needed to mitigate a crisis situation. Even in degraded post-disaster situations, the environment is scaled to the human world, requiring navigation of human obstacles such as doors and stairs, manipulation of human objects such as vehicles and power tools, and recognition of common human objects such as levers and valves ...
The use of sulfonated alkyl polyglucosides (SAPG) to replace lauryl sulfates and lauryl ether sulfates in sulfate-free formulations has previously been discussed. These primary surfactants were created with environmental and human safety in mind. The current paper describes more recent work with this material, specifically focusing on the lauryl version of SAPG.
Find genotoxicity testing articles on Environmental XPRT, the worlds largest environmental industry marketplace and information resource.
If ProMinent pumps are the heart of a system, ProMinent measuring and test systems are the brain. ProMinent refers to the use of measuring and control technology in liquid metering as 'intelligent metering'.
Pictures of Ames Tests for (A) Spontaneous Revertants and exposure to (B) Furylfuramide, (C) Alfatoxin B1, and (D) 2-Aminofluorene. The mutagenic compounds in B, C, and D were applied to the 6 mm filter disk in the center of each plate. Each Petri plate contains cells of the tester strain in a thin overlay of top agar. (The strain used here is TA98, derived by adding a resistance transfer factor to a Salmonella tester strain, mutant hisD3052, that scores frameshift mutations.) Plates C and D contain, additionally, a liver microsomal activation system isolated from rats. The spontaneous or compound-induced revertants, each of which reflects a mutational event, appear in a ring as spots around the paper disk. From Bruce N. Ames, Joyce McCann, and Edith Yamasaki, Methods for Detecting Carcinogens and Mutagens with the Salmonella/Mammalian-Microsomal Mutagenicity Test, Mutation Research 31 (1975): 358.. ...
An attempt was made to isolate the active component of Eriobotrya japonica, which inhibits aflatoxin B1-induced mutagenicity in the Salmonella assay system. The number of revertants per plate was significantly decreased when a MeOH extract of Eriobot
BioAssay record AID 200885 submitted by ChEMBL: Compound was tested for the mutagenicity activity in the Salmonella Typhimurium reverse mutation assay; +++-indicates the levels of mutagenicity as the number of revertant colonies obtained increases 10 times.
Abernethy DJ, Frazelle JH, Boreiko CJ [1982]. Effects of ethanol, acetaldehyde and acetic acid in the C3H/10T1/2 Cl 8 cell transformation system [Abstract Bf-1]. Environ Mutagen 4:331.. ACGIH [1986]. Industrial ventilation: a manual of recommended practice. 19th ed. Cincinnati, OH: American Conference of Governmental Industrial Hygienists.. American Cancer Society [1980]. Guidelines for the cancer-related check-up: recommendations and rationale. Cancer 30:4-50.. Ames BN, McCann J, Yamasaki E [1975]. Methods for detecting carcinogens and mutagens with the Salmonella /mammalian-microsome mutagenicity test. Mutat Res 31:347-363.. ANSI [1988]. American national standard fundamental governing the design and operation of local exhaust systems. New York, NY: American National Standards Institute, ANSI Z129.1-1988.. Asmussen E, Hald J, Larsen V [1948]. The pharmacological action of acetaldehyde on the human organism. Acta Pharmacol 4:311-320.. Auerbach C, Moutschen-Dahmen M Moutschen J [1977]. Genetic ...
The chromosome aberration test is designed to evaluate the potential of a test compound to induce structural chromosomal abnormalities such as breaks and exchanges.
Cancer persists as a worldwide disease and remains among the most common causes of death in the human population. Validated, dependable techniques that predict carcinogenic chemicals and provide information on human risk also remain elusive. A wide range of research methods have been explored, each aimed at predicting the carcinogenic potential of an untested chemical. For example, automated computer systems predict carcinogenicity based on mathematical models created by statistical analysis to correlate relationships between chemical structure similarities to a defined biological activity (Cunningham et al., 1998; Richard, 1998). In vitro methods such as the Salmonella mutagenicity assay and the micronucleus test are used to evaluate the ability of a compound to interact with DNA. Other mammalian cell-based assays have been implemented for nongenotoxic carcinogenicity predictions (Aardema et al., 1996; Foster, 1997). In vivo assays that reduce the term of the traditional 2-year bioassay, ...
Water quality - Determination of the genotoxicity of water and waste water - Salmonella/microsome fluctuation test (Ames fluctuation test)
1,3-Butadiene-Induced Adenine DNA Adducts Are Genotoxic but Only Weakly Mutagenic When Replicated in Escherichia coli of Various Repair and Replication Backgrounds ...
Discussion The results of this study indicate that chapéu-decouro (E. macrophyllus) extract is genotoxic and mutagenic to E. coli. The extract induced A prophage in the E. coli strain WP2s(A) and induced the expression of β-galactosidase in E. coli strain PQ37. The treatment of S. typhimurium strains CC103 and CC104 with chapéu-decouro extract indicated that GC sites may be the targets for mutagenic compounds since these strains are sensitive to base substitution at purine sites. ROS are deleterious to many organisms and have been implicated in aging and in degenerative diseases such as cancer (Harman, 1956; Valko et al., 2007). The consecutive univalent reduction of molecular oxygen to water produces three active intermediates: superoxide anion (O2.-), hydrogen peroxide (H2O2) and hydroxyl radical (OH.). These oxygen species are potent oxidants of lipids, proteins and nucleic acids, and may be related to the genotoxicity of several substances present in human foods (Ames and Gold, 1991). ...
Primary human hepatocyte cell line validated for genotoxicity micronucleus assays. Division-competent human hepatocytes that are easy to plate.
Carbon, Ability, Allium, Allium Cepa, Carbon Nanotubes, Concentrations, DNA, DNA Damage, Drosophila, Drosophila Melanogaster, Environment, Genotype, Health, Human, Mutagenicity Test, Mutation, Nanotubes, Recombination, Safety, Survival
The genotoxic potential of acrylamide monomer (AA), a compound familiar as a raw material of polyacrylamide electrophoresis gel, was extensively investigated in vitro. The results were clear cut: AA did not induce any gene mutations in Salmonella/microsome test systems (TA98, TA100, TA1535, TA1537), Escherichia coli/microsome assay (WP2 uvrA-) up to a dose of 50 mg AA/plate, or in HPRT-locus in Chinese hamster V79H3 cells (AA, 1-7 mM, 24 h treatment). On the other hand, AA showed a strong positive response: (a) in a Bacillus subtilis spore-rec assay (DNA damage) at 10-50 mg/disc, (b) to a chromosomal structural change test (AA, 2-5 mM, 24 h treatment), (c) to a polyploidy test (AA, 1-5 mM, 24 h treatment) in Chinese hamster V79H3 cells, (d) to a cell transformation assay in mouse BALB/c3T3 cells (AA, 1-2 mM, 72 h treatment). Sister chromatid exchange was also weakly but significantly induced by AA (AA, 1-2.5 mM, 24 h treatment) in Chinese hamster V79H3 cells. Carcinogenic potential of AA was ...
The objective of this study was to evaluate the potential of the test item to induce reverse mutations in Salmonella typhimurium. The study was performed according to the international guidelines (OECD No. 471 and Commission Directive No. B.13/14) and in compliance with the principles of Good Laboratory Practice. Methods A preliminary toxicity test was performed to define the dose levels of the test item, dissolved in dimethylsulfoxide (DMSO), to be used for the mutagenicity experiments. The test item was then tested in two independent experiments, both with and without a metabolic activation system, the S9 mix, prepared from a liver post-mitochondrial fraction (S9 fraction) of rats induced with Aroclor 1254. Treatments were performed according to the direct plate incorporation method except for the second experiment with S9 mix, which was performed according to the pre-incubation method (60 minutes, 37°C). Five strains of bacteria Salmonella typhimurium were used: TA 1535, TA 1537, TA 98, TA ...
Recently, investigators at Universität Ulm have been investigating the low molecular weight DNA diffusion assay (LMW assay) to measure cytotoxicity in comet assays.. The comet assay is a well-established in vitro and in vivo genotoxicity test. However, there has always been concern that the comet assay (as with all DNA strand break assays) may possibly detect exposure-related cytotoxicity rather than genotoxic effects. This is because DNA degradation is frequently involved in processes leading to cell death. Concurrent measures for cytotoxicity are required for standard genotoxicity testing to assess genotoxicity and to address possible effects of cytotoxicity in comet assay data interpretation.. Typically, histopathology has been accepted as a suitable cytotoxicity detection method when using the in vivo comet assay. By looking at the histology, levels of necrosis and apoptosis can be determined. However, there are other assays available for assessing cytotoxicity.. Here, the LMW assay has ...
Fecapentaenes are a class of conjugated ether lipids which have been identified as the major component of human fecal mutagenicity in the Ames Salmonella mutagenesis assay. Human epidemiologic data have indicated that most healthy North American populations eating a western diet do excrete detectable levels of fecapentaenes. Excreted fecapentaene levels seem to reflect levels throughout the colonic lumen, and levels vary characteristically between individuals. Those individuals found to excrete high levels of fecapentaene appear, based on limited data, to be at decreased risk of colorectal neoplasia. Carcinogenicity studies in rats and mice have been predominantly negative, however, increased tumor incidence in mice exposed to fecapentaenes as neonates has recently been reported. Fecapentaenes are direct-acting genotoxins, which may react with DNA through free radical mechanisms, and/or aldehyde formation. Mechanisms by which fecapentaene-induced DNA damage may mediate carcinogenesis are ...
Mutagenicity is a toxicity endpoint associated with the chronic exposure to chemicals. Aromatic amines have considerable industrial and environmental importance due to their widespread use in industry and their mutagenic capacity. Biopartitioning micellar chromatography (BMC), a mode of micellar liquid chromatography that uses micellar mobile phases of Brij35 in adequate experimental conditions, has demonstrated to be useful in mimicking the drug partitioning process into biological systems. In this paper, the usefulness of BMC for predicting mutagenicity of aromatic amines is demonstrated. A multiple linear regression (MLR) model based on BMC retention data is proposed and compared with other ones reported in bibliography. The proposed model present better or similar descriptive and predictive capability ...
Abstract from a paper by Ujvarosi et al. (2019), published in Chemospere : Microginins (MGs) are bioactive metabolites mainly produced by Microcystis spp., (Cyanobacteria) commonly found in eutrophic environments. In this study, the cytotoxic and genotoxic activities of four MG congeners (MG FR3, MG GH787, cyanostatin B, MGL 402) and a well characterized cyanobacterial extract…
In this lab simulation students conduct a modified Ames Test, which predicts carcinogenicity of chemicals. Students are provided with a virtual strain of Escherichia coli that is sensitive to (killed by) the antibiotic streptomycin, several virtual chemicals to test for mutagenicity, and two types of media (nutrient Agar and nutrient Agar + Streptomycin). The simulation allows students to propose a hypothesis about the types of chemicals that are likely to be mutagens and design an experiment to test their hypothesis.. ...
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The test uses several strains of the bacterium Salmonella typhimurium that carry mutations in genes involved in histidine synthesis i.e. it is a auxotrophic mutant, so that they require histidine for growth. The variable being tested is the mutagens ability to cause a reversion to growth on a histidine-free medium. The tester strains are specially constructed to have both frameshift and point mutations in the genes required to synthesize histidine, which allows for the detection of mutagens acting via different mechanisms. Some compounds are quite specific, causing reversions in just one or two strains.[3] The tester strains also carry mutations in the genes responsible for lipopolysaccharide synthesis, making the cell wall of the bacteria more permeable,[4] and in the excision repair system to make the test more sensitive.[5] Rat liver extract is optionally added to simulate the effect of metabolism, as some compounds, like benzo[a]pyrene, are not mutagenic themselves but their metabolic ...
RESULTS: A percentage of 36.17% controls and 38.6% patients were heterozygosis, considering Amplification-refractory mutation system (ARMS)-PCR assay while 23% and 22.85% were heterozygosis using Mismatch Amplification Mutation Assay (MAMA)-PCR. On the contrary, 1.3% and 1.4% were homozygosis A, while 75.7% and 75.75% presented homozygosis G, taking into account the MAMA-PCR results. The two assays were significantly different (P=0.0004 at χ2 Test), but MAMA-PCR showed a better performance for TNF-α -308 G/A gene polymorphism investigation ...
TY - JOUR. T1 - Genetic and epigenetic effects of environmental mutagens and carcinogens. AU - Pulliero, Alessandra. AU - Cao, Jia. AU - Vasques, Luciana Dos Reis. AU - Pacchierotti, Francesca. PY - 2015. Y1 - 2015. UR - http://www.scopus.com/inward/record.url?scp=84939522891&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=84939522891&partnerID=8YFLogxK. U2 - 10.1155/2015/608054. DO - 10.1155/2015/608054. M3 - Review article. C2 - 26345645. VL - 2015. SP - -. JO - BioMed Research International. JF - BioMed Research International. SN - 2314-6133. M1 - 608054. ER - ...
The protective effects of honey bee (HB) and pollen grains against cyclophosphamide (CPM) -induced cytotoxic and genotoxic effects in mice were investigated. This was achieved through study the effects of CPM and HB on oxidative status, chromosomal aberrations and gene expression of the tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), interleukin-1β (IL1β), interleukin 17A (IL-17A) and interferon-gamma (IFN-γ) in mice. In addition, the levels of reduced glutathione (GSH) and malondialdehyde were determined. The results of this study revealed that CPM decrease in GSH level and increase in malondialdehyde (MDA) level in the liver and kidney tissues. Moreover, CPM induced sperm abnormality, chromosomal aberrations and down regulated the expression of the studied cytokine genes. HB treatment in association with CPM ameliorates GSH, MDA, chromosomal aberrations and regulated the expression of IL-1-β, IL-17A, IL-6, TNF-α and IFN-γ. Thus, HB inhibits the cytotoxic and genotoxic risks ...
Founded in 1983, the Gentest brand initially focused on the use of cultured human cells in GLP genotoxicity assays. In 1985, the company expanded research activities into the area of xenobiotic metabolism by developing cytochrome P450 cDNA-expression approaches. This led to the first commercial offering of cDNA-expressed human cytochrome P450 enzymes in 1990. Since that time, the range of Gentest offerings has increased dramatically, from recombinant systems to in vivo-like systems like primary hepatocytes. Now, as part of Corning Life Sciences, the Gentest offerings continue to grow, helping you stay on the leading edge of drug discovery and development.. Our scientists are internationally recognized as leaders and innovators in cytochrome P450 cDNA-expression, in vitro xenobiotic metabolism, and drug transporter techniques. Our demonstrated commitment to research has been rewarded by the receipt of several competitive NIH grants. The results and applications of our research are reported in ...
The major impetus for developing the International Program for the Evaluation of Short-term Tests for Carcinogenicity (IPESTTC) was that our need for rapid identification and control of carcinogens...
No published study on the carcinogenicity of chlordimeform was available.. para-Chloro-ortho-toluidine, a metabolite of chlordimeform, was tested for carcinogenicity in two strains of mice and two strains of rats by oral administration in the diet. It was carcinogenic in both strains of mice, producing haemangiosarcomas. The studies in rats were not indicative of a carcinogenic effect, but certain limitations in their design were noted.. Chlordimeform is metabolized to a number of compounds, including para-chloro-ortho-toluidine, which has been identified in the urine of several animal species and of humans.. The available data were inadequate to evaluate the teratogenicity of chlordimeform to experimental animals.. Chlordimeform was negative in tests for DNA damage or mutagenicity in several cellular systems. No data were available, however, with regard to its mutagenicity in mammals, and no overall evaluation of the mutagenicity of chlordimeform could be made. ...
Safe Method of Use 13 Compounds that have Chronic Toxicity HSNO Categories 6.5 to 6.8 (Sensitisers, Carcinogenic Compounds, Mutagenic Compounds/ and Reproductive Toxins) HSNO Categories 6.5 to 6.8 (compounds
For a better understanding of the mechanism of foreign DNA mutagenesis, it is essential to study the validity of the changing DNA structure for manifestation of its mutagenic action on Drosophila melanogaster (method Basc). The testing of three different kinds of plasmid DNA has been carried out. The injections of only plasmid DNA pUC18 lead to a significant increase in the X-linked recessive lethal frequency. It is important to check mutagenicity of every new recombinant DNA.
Enviro-Mich message from Rane Curl ,[email protected], ------------------------------------------------------------------------- On Sun, 20 May 2001, David Zaber wrote: , , I would ask which "very useful" chemical has been banned due only to a , , positive result in the Ames assay? , , Dr. Curl wrote: , "Alar" , , Heres what Environmental Working Group has to say about the so-called , "Alar scare". , , "Prior to 1989, five separate, peer-reviewed studies of Alar and its , chemical breakdown product, UDMH, had found a correlation between , exposure to the chemicals and cancerous tumors in lab animals. In 1984 , and again in 1987, the EPA classified Alar as a probable human , carcinogen. In 1986, the American Academy of Pediatrics urged the EPA ...snip... It had been my understanding that alar was originally banned on the basis of the Ames test, and the animals tests followed. It appears that I was in error. This does not, however, concern my criticism of the misleading nature of the ...
Scientists from Brown University recently created a new approach for detecting mutations of single nucleotides within the RNA of HIV, such as the mutations that make HIV resistant to certain drugs.
Vogelstein and Tomasetti upset the environmental epidemiologists apple cart by using some statistical analysis of cancer risks related, essentially, to the number of cells at risk, their normal time of renewal by cell division, and age (time as correlated with number of cell divisions). Again simplifying, the number of at-risk actively dividing cells is correlated with the risk of cancer, as a function of age (reflecting time for cell mutational events), and with a couple of major exceptions like smoking, this result did not require including data on exposure to known mutagens. V and T suggested that the inherently imperfect process of DNA replication in cell division could, in itself, account for the age- and tissue-specific patterns of cancer. V and T estimated that except for the clear cases like smoking, a large fraction of cancers were not environmental in the primary causal sense, but were just due, as they said, to bad luck: the wrong set of mutations occurring in some line of body ...
In this interview, Wisner outlines Monsantos malice and blatant disregard for human safety as demonstrated in their own documents and even in their statements and behavior during the trial. Wisner explains how this evidence provided the basis for the enormous punitive damages award. Despite the recent reduction in Johnsons award, the judge upheld the verdict that Monsanto was acting with malice ...
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The articles by Basak, Majumdar, and Grunwald developed in silico models for the estimation of potential mutagenicity of chemicals from their structure without the input of any other experimental data.
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DDC classification: 1548,T Dissertation note: Piroxicam and Meloxicam are enolic acid derivatives and belong to oxicam class of non steroidal anti-inflammatory drugs. They are therapeutically used in rheumatoid arthritis and osteoarthritis. This study was designed to evaluate mutagenicity and cytotoxicity of piroxicam and meloxicam by Ames Salmonella/microsome mutagenicity assay and MTT assay. In this study, ten concentrations (100µg/ml, 300µg/ml, 500µg/ml, 700µg/ml, 900µg/ml, 1000µg/ml, 3000µg/ml, 5000µg/ml, 7000µg/ml and 10,000µg/ml) of piroxicam and meloxicam were used in Ames test against Salmonella strain TA100 in plate incorporation method, with and without metabolic activation S-9 mixture in triplicate manner. In MTT assay, confluent monolayer of BHK-21 cell lines was used and grown in 96-well cell culture plates treated with same concentrations of both drugs in triplicate manner. The results indicated that piroxicam had no mutagenic potential at concentrations of 100µg/plate ...
Olmesartan medoxomil. Olmesartan was not carcinogenic when administered by dietary administration to rats for up to 2 years. The highest dose tested (2000 mg/kg/day) was, on a mg/m 2 basis, about 480 times the maximum recommended human dose (MRHD) of 40 mg/day. Two carcinogenicity studies conducted in mice, a 6-month gavage study in the p53 knockout mouse and a 6-month dietary administration study in the Hras2 transgenic mouse, at doses of up to 1000 mg/kg/day (about 120 times the MRHD), revealed no evidence of a carcinogenic effect of olmesartan. Both olmesartan medoxomil and olmesartan tested negative in the in vitro Syrian hamster embryo cell transformation assay and showed no evidence of genetic toxicity in the Ames (bacterial mutagenicity) test. However, both were shown to induce chromosomal aberrations in cultured cells in vitro (Chinese hamster lung) and tested positive for thymidine kinase mutations in the in vitro mouse lymphoma assay. Olmesartan medoxomil tested negative in vivo for ...
An organic extract from fresh shrimp (Litopenaeus vannamei) was studied for antimutagenic and antiproliferative properties using Salmonella typhimurium tester strains TA98 and TA100 with metabolic activation (S9) and a cancer cell line (B-cell lymphoma), respectively. Shrimp extract was sequentially fractionated by thin layer chromatography (TLC) and each fraction was tested for antimutagenic and antiproliferative activities. Crude organic extracts obtained from shrimp reduced the number of revertants caused by aflatoxina B1, showing a dose-response type of relationship. Sequential TLC fractionation of the active extracts produced several antimutagenic and/or antiproliferative fractions. These results suggested that the lipid fraction of the tested species contained compounds with chemoprotective properties that reduce the mutagenicity of AFB1 and proliferation of a cancer cell line.
TY - JOUR. T1 - Inhibitory effect of saturated fatty acids on the mutagenicity of N-nitrosodimethylamine. AU - Negishi, Tomoe. AU - Hayatsu, Hikoya. PY - 1984. Y1 - 1984. N2 - Saturated fatty acids, C5C12, inhibited the mutagenic activity of N-nitrosodimethylamine (NDMA) in E. coli WP2 uvrA/pKM101. The inhibition by laurate (C12) was due to the suppression of the enzymatic demethylation of NDMA, whereas that by caprate (C10) was simply due to the bactericidal effect of the fatty acid. Caproate (C6) did not affect the NDMA-demethylase, and evidence is presented to show that the inhibition of mutagenesis by caproate was a result of its interference with the uptake of NDMA metabolites into bacterial cells. Possible biological significance of the inhibition is discussed.. AB - Saturated fatty acids, C5C12, inhibited the mutagenic activity of N-nitrosodimethylamine (NDMA) in E. coli WP2 uvrA/pKM101. The inhibition by laurate (C12) was due to the suppression of the enzymatic demethylation of NDMA, ...
24 A study investigated anti-mutagenic. activity of H. antidysenterica, where methanolic bark extract of the plant demonstrated anti-mutagenic potency in sodium azide and methyl methane sulphonate induced mutagenicity in Salmonella typhimurium strains. 25 Plants with anti-hypertensive activity are investigated on their ability to inhibit the secretion of angiotensin, which causes vasoconstriction leading to increased blood pressure. Ethanolic seed extracts showed a satisfactory 24% angiotensin-converting enzyme (ACE) inhibition.26 Bark extracts tested for in vitro and in vivo anti-malarial Luminespib in vivo activity against Plasmodium falciparum isolates and P. berghei infected Swiss mice respectively, showed significant results. 27 Chloroform bark extract demonstrated the greatest anti-plasmodial activity, with an average IC50 value of 5.7 μg/ml in the in vitro experiment and 70% suppression of parasitaemia in the in vivo experiment when administered at 30 mg/kg. 27 Most of the known chemical ...
The Comet Assay, also called single cell gel electrophoresis (SCGE), is a sensitive and rapid technique for quantifying and analyzing DNA damage in individual cells.
Half the population in the world is chronically infected with H.pylori. This infection has been proven to be associated with gastritis, duodenal and gastric ulcers but also with gastric cancer and MALT-lymphoma. The aims of this thesis were to explore some possible mechanisms by which H.pylori may contribute to the onset of gastric cancer.. The first approach was to study whether H. pylori is mutagenic. Three different H.pylori strains (NCTC 11637, Ca 18, 13/12), all cagA and VacApositive, were studied with the Salmonella mutagenicity assay (the Ames test). No dose-response curve and no increase in revertants were seen. These results show that H. pylori is not likely to be mutagenic.. A special feature ofH.pylori gastritis is that it is practically always linked to inflammation with varying degrees of mucosal activity. Neutrophils and monocytes produce and liberate nitric oxide and oxygen radicals, which are capable of inducing mutations of DNA. In order to test if the bacterium alone or ...
GENE-TOX provides genetic toxicology (mutagenicity) test data from expert peer review of open scientific literature for more than 3,000 chemicals from the United States Environmental Protection Agency (EPA). GENE-TOX was established to select assay systems for evaluation, review data in the scientific literature, and recommend proper testing protocols and evaluation procedures for these systems. GENE-TOX covers the years 1991 - 1998. It is no longer updated.. ...
A HPLC-ESI-IT-MSn method, based on high-performance liquid chromatography coupled to electrospray negative ionization multistage ion trap mass spectrometry, was developed for rapid identification of 24 flavonoid and naphthopyranone compounds. The methanol extracts of the capitulae and scapes of P. chiquitensis exhibited mutagenic activity in the Salmonella/microsome assay, against strain TA97a.
Two-year feeding studies in mice and rats conducted under the auspices of the National Toxicology Program (NTP) uncovered no evidence of a carcinogenic potential of hydrochlorothiazide in female mice (at doses of up to approximately 600 mg/kg/day) or in male and female rats (at doses of approximately 100 mg/kg/day). The NTP, however, found equivocal evidence for hepato-carcinogenicity in male mice. Hydrochlorothiazide was not genotoxic in vitro in the Ames mutagenicity assay of Salmonella typhimurium strains TA 98, TA100, TA 1535, TA 1537, and TA 1538 and in the Chinese Hamster Ovary (CHO) test for chromosomal aberrations, or in vivo in assays using mouse germinal cell chromosomes, Chinese hamster bone marrow chromosomes, and the Drosophila sex-linked recessive lethal trait gene. Positive test results were obtained only in the in vitro CHO Sister Chromatid Exchange (clastogenicity) and in the Mouse Lymphoma Cell (mutagenicity) assays, using concentrations of hydrochlorothiazide from 43 to 1300 ...
An investigation into the effects of aneugens in the mouse lymphoma assay - a genetic toxicological assay for mamaalian gene mutation ...
The long history of herbal prescriptions seems that they are nontoxic and clinically effective. However, for present medicinal therapeutics, there have been few scientific studies undertaken to determine the safety of traditional medicinal herbs. Therefore, concerns have been raised about the lack of scientific evidence for the safety of herbal medicines [17]. SCRT was proven to be safe in a 90-day oral toxicity study in rats [18]. In a series of safety evaluations for SCRT, a genotoxicity test was conducted in the present work to check its capacity for mutagenicity. Here, we performed to detect chromosome aberrations in CHL cells, a bacterial reverse mutation test using the S. typhimurium/E. coli incorporation assay (Ames test), and an in vivo micronucleus test recommended by the KFDA. We evaluated acute toxicity using the standard battery of tests recommended by the KFDA. The present study was performed according to OECD guidelines for the testing of chemicals in accordance with modern Good ...
The Ames test is a widely employed method that uses bacteria to test whether a given chemical can cause mutations in the DNA of the test organism. More formally, it is a biological assay to assess the mutagenic potential of chemical compounds. A positive test indicates that the chemical is mutagenic and therefore may act as a carcinogen, because cancer is often linked to mutation. The test serves as a quick and convenient assay to estimate the carcinogenic potential of a compound because standard carcinogen assays on mice and rats are time-consuming (taking two to three years to complete) and expensive. However, false-positives and false-negatives are known. The procedure was described in a series of papers in the early 1970s by Bruce Ames and his group at the University of California, Berkeley. The Ames test uses several strains of the bacterium Salmonella typhimurium that carry mutations in genes involved in histidine synthesis. These strains are auxotrophic mutants, i.e. they require ...
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Health Canada Paul White is a research scientist at Health Canada, and an adjunct professor of biology at the University of Ottawa. He completed his PhD at McGill University in Montreal, and conducted post-doctoral research at the US Environmental Protection Agency laboratories in Narragansett, Rhode Island and Research Triangle Park, North Carolina. His research focuses on the detection, sources, fate and hazards of mutagenic and carcinogenic substances, including those present in complex environmental matrices such as urban air, vehicle exhaust, house dust, and contaminated soils. His current work is investigating the mutagenic hazards of complex PAH mixtures, the suitability of various in vitro and in vivo approaches for effective assessment of genetic toxicity, and the use of quantitative methods for the analysis and interpretation of genetic toxicity dose-response data. Interpretation of Genetic Toxicity Benchmark Dose (BMD) Values - Comparisons Across Covariates, Determination of ...
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The aim of the present study was to investigate the antimutagenic effects of chrysin (CR), a flavonoid compound contained in many fruits, vegetables and honey. Earlier investigations with bacterial indicators showed that CR is one of the most potent antimutagens among the flavonoids. In the present study, we tested the compound in the Salmonella strains TA98 and TA100 in combination with benzo(a)pyrene (B(a)P) and 2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP) and found pronounced protective activity over a concentration range between 10 and 100 microg/ml. The compound itself was devoid of mutagenic activity at all concentrations tested. In the micronucleus (MN) assay with human-derived HepG2 cells, a different pattern of activity was seen. CR itself caused significant induction of MN at dose levels > or =15 microg/ml; in combination experiments with B(a)P and PhIP, U-shaped dose-response curves were obtained and protection was found only in a narrow dose range (5 - 10 microg/ml). Our ...
Literature References: Prepn: O. C. Billeter, Ber. 38, 2015 (1905). Mutagenicity studies: T. Alderson, Nature 207, 164 (1965); J. B. Jenkins, Mutat. Res. 4, 90 (1967); A. P. Schalet, ibid. 49, 313 (1978). Review of carcinogenicity studies: IARC Monographs 7, 245-252 (1974). Review of comparative mutagenicity of EMS and methyl methanesulfonate, q.v.: S. Kondo, Environ. Sci. Res. 24, 743-785 (1981). ...