Biomedical subjects

Larry D Claxton

Publications and source records attributed to Larry D Claxton.

13 recordsLinked to original sources

PubMed2006

Mutagenic compounds generated from the chlorination of disperse azo-dyes and their presence in drinking water.

The water produced by the Cristais River Drinking Water Treatment Plant (CR-DWTP) repeatedly produced mutagenic responses that could not be explained by the presence of disinfection byproducts (DBPs) generated by the reaction of humic acids and chlorine. In order to determine the possible role of chlorinated dye products in this mutagenic activity, solutions of a black dye commercial product (BDCP) composed of C.I. Disperse Blue 373, C.I. Disperse Orange 37, C.I. Disperse Violet 93, and chemically reduced BDCP (R-BDCP) were chlorinated in a manner similar to that used by the CR-DWTP. The resulting solutions were extracted with XAD-4 along with one drinking water sample collected from the CR-DWTP. All extracts showed mutagenic activity in the Salmonella/microsome assay. Dye components of the BDCP as well as its reduced chlorinated (CI-R-BDCP) derivative were detected in the drinking water sample by analysis with a high performance liquid chromatography/diode array detector (HPLC/DAD). The mutagenicity results of these products suggest that they are, at least in part, accounting for the mutagenic activity detected in the drinking water samples from the Cristais River. The data obtained in this study have environmental and health implications because the chlorination of the BDCP and the R-BDCP leads to the formation of mutagenic compounds (CI-BDCP and CI-R-BDCP), which are potentially important disinfection byproducts that can contaminate the drinking water as well as the environment.

Chlorine↗

PubMed2006

The mutation spectra of chlorinated drinking water samples using the base-specific TA7000 strains of Salmonella in the microsuspension assay.

Mutation spectra analysis can provide important information about the types of genotoxic compounds that can be present in environmental samples. In this study, we used the TA7000 base-specific Salmonella typhimurium tester strains to characterize water samples from two drinking water treatment plants (DWTPs) in São Paulo, Brazil. Because of the small sample sizes of these environmental samples, the use of the microsuspension protocol was necessary. Acidic extracts of drinking water samples from the two DWTPs gave similar responses in the TA7000 strains and caused primarily CG to AT transversions. It is likely that halogenated disinfection by-products, generated during the chlorination of water, are causing the response seen with the TA7000 strains.

Animals↗

PubMed2006

Evaluation of new 2,2'-dimethyl-5,5'-dipropoxybenzidine- and 3,3'-dipropoxybenzidine-based direct dye analogs for mutagenic activity by use of the Salmonella/mammalian mutagenicity assay.

As part of a continuing study aimed at establishing structure-activity relationships and heuristic principles useful for the design of non-genotoxic azo dyes, a series of new direct dyes based on two non-mutagenic benzidine analogs, 2,2'-dimethyl-5,5'-dipropoxybenzidine and 3,3'-dipropoxybenzidine, were evaluated for mutagenic activity in Salmonella typhimurium strains TA98 and TA100. These strains are widely used for mutagenicity screening and have been shown to detect the mutagenic activity of benzidine analogs. While some toxicity was seen with some dyes at high doses, all of the dyes examined were judged non-mutagenic with and without metabolic activation in the standard Salmonella plate-incorporation assay. The results in the standard test are consistent with the properties of the diamines themselves. However, only one of the dyes was non-mutagenic when a reductive-metabolism pre-incubation assay was used. The results of this study suggest that although benzidine analogs are potential replacements for benzidine, there is a need to understand which mutagenic products are produced when reductive metabolism is present. There is also a need to know whether or not metal complexes of these dyes are mutagenic. Such information will allow the development of new non-mutagenic azo dyes.

Animals↗

PubMed2005

Review of the Salmonella typhimurium mutagenicity of benzidine, benzidine analogues, and benzidine-based dyes.

We have reviewed the mutagenicity of benzidine analogues (including benzidine-based dyes), with a primary emphasis on evaluating results of the Salmonella/microsome mutagenicity assay. Many of these amines are mutagenic in tester strains TA98 and TA100 but require exogenous mammalian activation (S9) for activity. A few amines with halogen or nitro-groups in the structure are direct-acting mutagens. The addition of a sulfonic acid moiety to the molecule of benzidine reduced the mutagenicity of benzidine; whereas, methoxy, chloro, or methyl group additions did not. Complexation with a metal ion also decreased the mutagenicity. A substitution of an alkyl group on the ortho position next to an amine group also influenced the mutagenicity. Most carcinogenic benzidine analogues are mutagenic, and their metabolism to electrophiles that interact with DNA, leading to mutations, plays a central role in their carcinogenesis.

Animals↗

PubMed2005

The contribution of azo dyes to the mutagenic activity of the Cristais River.

To verify whether dyes emitted within the discharge of a dye processing plant were contributing to the mutagenicity repeatedly found in the Cristais River, Sao Paulo, Brazil, we chemically characterized the following mutagenic samples: the treated industrial effluent, raw and treated water, and the sludge produced by a Drinking Water Treatment Plant (DWTP) located approximately 6 km from the industrial discharge. Considering that 20% of the dyes used for coloring activities might be lost to wastewaters and knowing that several dyes have mutagenic activity, we decided to analyze the samples for the presence of dyes. Thin layer chromatographic analysis indicated the presence of three prevalent dyes in all samples, except for the drinking water. This combination of dyes corresponded to a commercial product used by the industry, and it tested positive in the Salmonella assay. The structures of the dye components were determined using proton magnetic resonance and mass spectrometric (MS) methods, and the dyes were tested for mutagenicity. The blue component was identified as the C.I. Disperse Blue 373, the violet as C.I. Disperse Violet 93, and the orange as C.I. Disperse Orange 37. The dyes showed mutagenic responses of 6300, 4600, and 280 revertants/microg for YG1041 with S9 respectively. A bioassay-directed fractionation/chemical analysis showed that the C.I. Disperse Blue 373 contributed 55% of the mutagenic activity of the DWTP sludge. We showed that these dyes contributed to the mutagenic activity found in the Cristais River environmental samples analyzed and are indirectly affecting the quality of the related drinking water. Therefore, we believe that this type of discharge should be more thoroughly characterized chemically and toxicologically. Additionally, human and ecological risks associated with the release of dye processing plant effluents should be more fully investigated, especially where the resultant water is taken for human consumption.

Animals↗

PubMed2005

Mutagenicity evaluation of the commercial product CI Disperse Blue 291 using different protocols of the Salmonella assay.

Textile dyes can enter the water ecosystem through wastewater discharges potentially exposing humans through the consumption of water and food. The commercial disperse dye product CI Disperse Blue 291 containing the aminoazobenzene 2-[(2-bromo-4,6-dinitrophenyl)azo]-5-(diethylamino)-4-methoxyacetanilide (CAS registry no. 56548-64-2) was tested for mutagenic activity in the Salmonella assay. We used strains with different levels of nitroreductase and O-acetyltransferase (i.e., TA98DNP6, YG1024, and YG1041) that are relevant enzymes in the activation of nitrocompounds by the intestinal microflora. The commercial product tested also was mutagenic for TA1537, TA1538, TA98 and TA100. Presence of the pKM101 plasmid and the addition of S9 enhanced the mutagenic response. Specialized strains showed that both nitroreductase and O-acetyltransferase are important in activation of the product. The highest potency obtained was 240 revertants per microgram for YG1041 in the presence of S9. Besides being able to cause frameshift mutations (hisd3052), the dye was able to cause all types of base pair substitution with a preference for TA to AT; CG to TA and CG to AT changes. With these results clearly showing that the bacterial nitroreductase and O-acetyltransferase metabolites of this compound are mutagenic, there is a need to test this dye using in vivo systems to verify possible adverse effects of this product in mammalian tissues.

Acetanilides↗

PubMed2005

Scientific authorship. Part 2. History, recurring issues, practices, and guidelines.

One challenge for most scientists is avoiding and resolving issues that center around authorship and the publishing of scientific manuscripts. While trying to place the research in proper context, impart new knowledge, follow proper guidelines, and publish in the most appropriate journal, the scientist often must deal with multi-collaborator issues like authorship allocation, trust and dependence, and resolution of publication conflicts. Most guidelines regarding publications, commentaries, and editorials have evolved from the ranks of editors in an effort to diminish the issues that faced them as editors. For example, the Ingelfinger rule attempts to prevent duplicate publications of the same study. This paper provides a historical overview of commonly encountered scientific authorship issues, a comparison of opinions on these issues, and the influence of various organizations and guidelines in regards to these issues. For example, a number of organizations provide guidelines for author allocation; however, a comparison shows that these guidelines differ on who should be an author, rules for ordering authors, and the level of responsibility for coauthors. Needs that emerge from this review are (a) a need for more controlled studies on authorship issues, (b) an increased awareness and a buy-in to consensus views by non-editor groups, e.g., managers, authors, reviewers, and scientific societies, and (c) a need for editors to express a greater understanding of authors' dilemmas and to exhibit greater flexibility. Also needed are occasions (e.g., an international congress) when editors and others (managers, authors, etc.) can directly exchange views, develop consensus approaches and solutions, and seek agreement on how to resolve authorship issues. Open dialogue is healthy, and it is essential for scientific integrity to be protected so that younger scientists can confidently follow the lead of their predecessors.

Authorship↗

PubMed2005

Scientific authorship. Part 1. A window into scientific fraud?

The examination of a single scientific manuscript seldom alerts scientists, reviewers, editors, and scientific administrators to the fabrication and falsification of data and information. This review shows that most documented cases of scientific fraud involve falsification (altering truthful information) and fabrication (inventing information where none previously existed). Plagiarism is much less frequent. The review of published accounts also shows that the publication of scientific papers containing recognizable fraudulent material is very low, probably less than 0.02% and extremely difficult to detect. Because most reported cases of fraud have involved research done at prestigious organizations with distinguished co-authors, and that is published in journals with exacting review processes, it becomes evident that some unscrupulous scientists are adept at fabricating and falsifying data. However, "significant" scientific fraud is detected when scientists repeatedly report results that cannot be independently verified, when colleagues report suspicious behavior, or scientific audits are performed. This review documents and compares many of the better-known cases of scientific fraud. Fraudulent behavior has served as the impetus for the scientific community to develop publication procedures and guidelines that help to guard against not only fraudulent behavior but also against other types of unethical or undesirable behaviors. A companion paper reviews the non-fraudulent issues associated with scientific publication.

Authorship↗

PubMed2005

Biodegradation of simple chemical mixtures in soil.

Exogenous microorganisms often are used to enhance bioremediation. This study compared the capabilities of two exogenous microbial cultures and an indigenous population to detoxify a Weswood silt loam soil amended with a simple chemical mixture. The first three treatments were unamended soils inoculated with either indigenous microorganisms, Pseudomonas aeruginosa, or Phanerochaete sordida. Three additional treatments consisted of soil amended with benzo[a]pyrene, pentachlorophenol, and 2,4,6-trinitrotoluene, which were inoculated with either indigenous microorganisms, P. aeruginosa, or P. sordida. Samples were collected from the soils at several time points from 0 through 540 or 720 d, sequentially extracted with methylene chloride and methanol, and analyzed for genotoxicity (using the Salmonella/microsome assay) and chemical degradation. Although the indigenous microorganisms were effective for removal of benzo[a]pyrene, the Pseudomonas bacteria exhibited slightly greater removal rates for 2,4,6,-trinitrotoluene. The fungal cultures were significantly more effective at degrading pentachlorophenol. The day 540 extracts from all model chemical-amended treatments were genotoxic. In most cases, the day 540 extracts were more genotoxic than the day 0 extracts. The results suggest that, under appropriate conditions, enriched cultures of microorganisms may have an increased capacity to degrade individual chemicals. However, the products of degradation in some cases might be more genotoxic than the parent compounds.

Biodegradation, Environmental↗

PubMed2004

Developing azo and formazan dyes based on environmental considerations: Salmonella mutagenicity.

In previous papers, the synthesis and chemical properties of iron-complexed azo and formazan dyes were reported. It was shown that in certain cases iron could be substituted for the traditionally used metals such as chromium and cobalt, without having an adverse effect on dye stability. While these results suggested that the iron analogs were potential replacements for the commercially used chromium and cobalt prototypes, characterization of potentially adverse environmental effects of the new dyes was deemed an essential step in their further development. The present paper provides results from using the Salmonella/mammalian microsome assay to determine the mutagenicity of some important commercial metal complexed dyes, their unmetallized forms, and the corresponding iron-complexed analogs. The study compared the mutagenic properties of six unmetallized azo dyes, six commercial cobalt- or chromium-complexed azo dyes, six iron-complexed azo dyes, six unmetallized formazan dyes, and six iron-complexed formazan dyes. The results of this study suggest that the mutagenicity of the unmetallized dye precursors plays a role in determining the mutagenicity of the iron-complexes. For the monoazo dye containing a nitro group, metal complex formation using iron or chromium decreased or removed mutagenicity in TA100; however, little reduction in mutagenicity was noted in TA98. For the formazan dye containing a nitro group, metal-complex formation using iron increased mutagenicity. Results varied for metal-complexes of azo and formazan dyes without nitro groups, but in general, the metal-complexed dyes based on mutagenic ligands were also mutagenic, while those dyes based on nonmutagenic ligands were nonmutagenic.

Azo Compounds↗

PubMed2004

Investigating the sources of the mutagenic activity found in a river using the Salmonella assay and different water extraction procedures.

In the routine São Paulo state (Brazil) surface water quality-monitoring program, which includes the Salmonella microsome mutagenicity assay as one of its parameters, a river where water is taken and treated for drinking water purposes has repeatedly shown mutagenic activity. A textile dyeing facility employing azo-type dyes was the only identifiable source of mutagenic compounds. We extracted the river and drinking water samples with XAD4 at neutral and acidic pH and with blue rayon, which selectively adsorbs polycyclic compounds. We tested the industrial effluent, raw, and treated water and sediment samples with YG1041 and YG1042 and compared the results with the TA98 and TA100 strains. The elevated mutagenicity detected with YG-strains suggested that nitroaromatics and/or aromatic amines were causing the mutagenicity detected in the samples analyzed. Positive responses for the blue rayon extracts indicated that mutagenic polycyclic compounds were present in the water samples analyzed. The mutagen or mixture of mutagens present in the effluent and water samples cause mainly frameshift mutations and are positive with and without metabolic activation. The Salmonella assay combined with different extraction procedures proved to be very useful in the identification of the origin of the pollution and in the identification of the classes of chemical compounds causing the mutagenic activity in the river analyzed.

Brazil↗

PubMed2004

The genotoxicity of ambient outdoor air, a review: Salmonella mutagenicity.

Mutagens in urban air pollution come from anthropogenic sources (especially combustion sources) and are products of airborne chemical reactions. Bacterial mutation tests have been used for large, multi-site, and/or time series studies, for bioassay-directed fractionation studies, for identifying the presence of specific classes of mutagens, and for doing site- or source-comparisons for relative levels of airborne mutagens. Early research recognized that although carcinogenic PAHs were present in air samples they could not account for the majority of the mutagenic activity detected. The mutagenicity of airborne particulate organics is due to at least 500 identified compounds from varying chemical classes. Bioassay-directed fractionation studies for identifying toxicants are difficult to compare because they do not identify all of the mutagens present, and both the analytical and bioassay protocols vary from study to study. However, these studies show that the majority of mutagenicity is usually associated with moderately polar/highly polar classes of compounds that tend to contain nitroaromatic compounds, aromatic amines, and aromatic ketones. Smog chamber studies have shown that mutagenic aliphatic and aromatic nitrogen-containing compounds are produced in the atmosphere when organic compounds (even non-mutagenic compounds) are exposed to nitrogen oxides and sunlight. Reactions that occur in the atmosphere, therefore, can have a profound effect on the genotoxic burden of ambient air. This review illustrates that the mutagenesis protocol and tester strains should be selected based on the design and purpose of the study and that the correlation with animal cancer bioassay results depends upon chemical class. Future emphasis needs to be placed on volatile and semi-volatile genotoxicants, and on multi-national studies that identify, quantify, and apportion mutagenicity. Initial efforts at replacing the Salmonella assay for ambient air studies with some emerging technology should be initiated.

Air Pollutants↗

PubMed2004

Mutagens in contaminated soil: a review.

The intentional and accidental discharges of toxic pollutants into the lithosphere results in soil contamination. In some cases (e.g., wood preserving wastes, coal-tar, airborne combustion by-products), the contaminated soil constitutes a genotoxic hazard. This work is a comprehensive review of published information on soil mutagenicity. In total, 1312 assessments of genotoxic activity from 118 works were examined. The majority of the assessments (37.6%) employed the Salmonella mutagenicity test with strains TA98 and/or TA100. An additional 37.6% of the assessments employed a variety of plant species (e.g., Tradescantia clone 4430, Vicia faba, Zea mays, Allium cepa) to assess mutagenic activity. The compiled data on Salmonella mutagenicity indicates significant differences (p<0.0001) in mean potency (revertents per gram dry weight) between industrial, urban, and rural/agricultural sites. Additional analyses showed significant empirical relationships between S9-activated TA98 mutagenicity and soil polycyclic aromatic hydrocarbon (PAH) concentration (r2=0.19 to 0.25, p<0.0001), and between direct-acting TA98 mutagenicity and soil dinitropyrene (DNP) concentration (r2=0.87, p<0.0001). The plant assay data revealed excellent response ranges and significant differences between heavily contaminated, industrial, rural/agricultural, and reference sites, for the anaphase aberration in Allium cepa (direct soil contact) and the waxy locus mutation assay in Zea mays (direct soil contact). The Tradescantia assays appeared to be less responsive, particularly for exposures to aqueous soil leachates. Additional data analyses showed empirical relationships between anaphase aberrations in Allium, or mutations in Arabidopsis, and the 137Cs contamination of soils. Induction of micronuclei in Tradescantia is significantly related to the soil concentration of several metals (e.g., Sb, Cu, Cr, As, Pb, Cd, Ni, Zn). Review of published remediation exercises showed effective removal of genotoxic petrochemical wastes within one year. Remediation of more refractory genotoxic material (e.g., explosives, creosote) frequently showed increases in mutagenic hazard that remained for extended periods. Despite substantial contamination and mutagenic hazards, the risk of adverse effect (e.g., mutation, cancer) in humans or terrestrial biota is difficult to quantify.

Industrial Waste↗