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The metal-mediated formation of hydroxyl radical by aqueous extracts of cigarette tar.

Aqueous extracts of cigarette tar produce hydroxyl radicals that are spin trapped by 5,5-dimethyl-1-pyrroline-N-oxide. The addition of catalase almost completely inhibits and superoxide dismutase partially inhibits spin adduct formation. The addition of ethylenediamine tetraacetic acid greatly increases the amount of hydroxyl radical adduct observed; in contrast, diethylenetriamine pentaacetic acid causes complete inhibition of spin adduct formation. We suggest that the hydroxyl radical arises from the metal-mediated decomposition of hydrogen peroxide, and that hydrogen peroxide is formed from the reduction of dioxygen by the semiquinones present in the cigarette tar.

Catalase↗

Aqueous cigarette tar extracts damage human alpha-1-proteinase inhibitor.

The elastase inhibitory capacity (EIC) of human alpha-1-proteinase inhibitor (alpha 1PI) is severely compromised by aqueous cigarette tar extract (ACTE). An aqueous extract of the tar from two cigarettes causes a loss of EIC of at least 60% in 24 h at 37 degrees C (pH 7.4) and the damaging capability of the ACTE is retained for many hours. Hydrogen peroxide appears to be an essential component of the mechanism by which ACTE damages alpha 1 PI, since catalase substantially protects alpha 1PI from ACTE-mediated damage. Only mild protection is offered by 10 mM diethylenetriamine pentaacetic acid, indicating only a minor role for transition metal ions in the alpha 1PI-damaging process. Hydroxyl radicals are unlikely agents of alpha 1PI damage in the ACTE system, as judged from hydroxyl radical scavenger studies. Ascorbate and various thiols offer protection to different degrees, dependent on the incubation conditions. Of several amino acids tested, cysteine and methionine (but not methionine sulfoxide) are the only two that protect alpha 1PI. We suggest that components of cigarette smoke particulate matter extracted into the aqueous lung fluid environment may cause local deficiencies in alpha 1PI in smokers' lungs.

Amino Acids↗

The histopathologic features which follow repeated applications of tobacco tar to rat lip mucosa.

The response of rat lip mucosa to two tobacco tar preparations combined with heat was examined histopathologically. It was shown that the magnitude of irritational hyperplasia produced was related to the level of irritation. This was greatest in those rats subjected to the longest period of application of the tobacco extract with the greatest concentration of tar combined with heating the site of application. Neoplastic changes were not produced.

Animals↗

Tar, CO and delta 9THC delivery from the 1st and 2nd halves of a marijuana cigarette.

Previous in vitro studies suggest that, with successive puffs from a marijuana cigarette, delta-9-THC becomes concentrated in the remaining uncombusted portion of the cigarette. These observations are consistent with the common practice of smoking marijuana cigarettes to a smaller butt length than that to which tobacco cigarettes are smoked. The purpose of the present study was to compare the delivery of delta-9-THC, as well as total insoluble smoke particulates (tar) and carbon monoxide, from the distal ("first") versus the proximal ("second") halves of a standard marijuana cigarette during "natural" smoking of marijuana. On 4 separate days, ten habitual marijuana users smoked nearly all or approximately 1/2 of a standard marijuana cigarette (83 mm length; 800-900 mg; 1.24% THC), as follows: day 1, "whole" cigarette (60 mm smoked, leaving a 23-mm butt); day 2, "first" half (first 30 mm); day 3, "second" half (second 30 mm) after the "first" half was presmoked with a syringe; and day 4, "second" half after the "first" half was excised. A previously described smoking apparatus (20) was used for measurement of puff volume and inhaled tar. Puff volume and number were allowed to vary spontaneously (provided that the specified length of cigarette was consumed), while inhaled volume (1.5 liters), breathholding time (14 s) and interpuff interval (30 s) were held constant. Blood samples were withdrawn prior to smoking and serially after completion of smoking for analysis of blood carboxyhemoglobin (COHb) and serum delta-9-THC. Heart rate was measured before and 5 min after smoking. Subjects rated their level of "high" 20 min after completion of smoking.(ABSTRACT TRUNCATED AT 250 WORDS)

Carbon Monoxide↗

Polycyclic aromatic hydrocarbon-DNA and protein adducts in coal tar treated patients and controls and their relationship to glutathione S-transferase genotype.

Coal tar treated psoriasis patients were used as a model population to evaluate a panel of immunoassays for monitoring exposure to benzo[a]pyrene (BP) and related polycyclic aromatic hydrocarbons (PAH). The assays included measurement of PAH diol epoxide-DNA adducts in white blood cells by competitive enzyme-linked immunosorbent assay (ELISA) with fluorescence endpoint detection, PAH-albumin adducts by competitive ELISA with color endpoint detection and serum levels of antibodies recognizing BP diol epoxide-DNA adducts by noncompetitive color ELISA. PAH-DNA adducts by ELISA were elevated in patients (mean 6.77 +/- 12.05/10(8)) compared to controls (4.90 +/- 8.81/10(8), p = 0.12). There was no difference in PAH-albumin adducts between patients (mean 0.61 +/- 0.31 fmol/micrograms) and controls (0.63 +/- 0.30 fmol/micrograms). Glutathione S-transferase M1 genotype was also determined but no relationship was found between presence of the gene and either DNA or protein adduct levels. About 30% of both patients and controls had measurable titer of antibodies recognizing BPDE-I-DNA adducts. Measurement of white blood cell DNA adducts by ELISA was the most sensitive method for detecting PAH exposure in coal tar-treated psoriasis patients.

Benzo(a)pyrene↗

Suppression of mutation induction and failure to detect mutagenic activity with athabasca tar sand fractions.

5 different histidine-requiring strains of Salmonella typhimurium were used to test the mutagenic activity of 7 different fractions of Athabasca tar-sand. None of the 7 fractions (bitumen, maltenes, asphaltenes, saturated, monoaromatic, diaromatic and polyaromatic hydrocarbons), showed positive mutagenic response in any of the Salmonella typhimurium strains. We have tested a wide range of concentrations. The results obtained so far are consistent with the lack of mutagenic activity of all investigated fractions in the absence and in the presence of metabolic activation. Assuming that there might be an association between the absence of mutagenic activity and the complexity of the tar-sand fractions, we investigated the effect of the polyaromatic hydrocaron fraction on the mutagenicity of the carcinogenic agent 2-aminoanthracene. The data obtained indicate clearly that the polyaromatic hydrocarbon fraction suppresses the mutagenic activity of 2-aminoanthracene.

Dose-Response Relationship, Drug↗

Determining the mutagenic activity of a tar, its vapors and aerosols.

The Ames test was performed on Salmonella typhimurium, strain TA98, TA100, TA1535, TA1537, TA1538, to evaluate the mutagenic potential of a tar as well as its vapors and aerosols emitted at 250, 350 and 550 degrees C. Two chemical procedures were used: extractions of aromatics for DMSO; elimination of acids, alcohols and phenols. Weak mutagenic activity was demonstrated at each temperature. Then, using only Salmonella typhimurium strains TA98 and TA100, a study was made on the effects of the mutagenic compounds, benzo[a]pyrene, 2-aminoanthracene, nitrofluorene, methyl methanesulfonate and on the vapors and aerosols emitted at 350 degrees C by road-coating tar. For promutagenic compounds, an enhancing effect was observed before an inhibition effect. For direct mutagenic compounds, only the inhibition effect appeared. The mutagenic and/or carcinogenic activity was usually tested on a pure isolated chemical compound.

Aerosols↗

Detection of volatile mutagens in creosote and coal tar.

Creosote and coal tar were examined for the presence of volatile mutagens by use of the so-called "taped plate assay". Application of this method, recently published by Distlerath et al., reveals that vapour escaping from creosote and coal tar at 37 degrees C was able to revert the Salmonella typhimurium strains TA98 and TA100 in the presence of S9 mix. The simplicity of this method makes it useful for routine screening of industrial fluids or solid products for the presence of volatile mutagens.

Animals↗

Fluoranthene, a volatile mutagenic compound, present in creosote and coal tar.

Creosote, a coal-tar distillation product, contains mutagens which are volatile at 37 degrees C. After distillation of creosote we found that these volatile mutagens were present in the distillation fraction with the highest boiling range (greater than 360 degrees C). The "volatile mutagenic activity" was connected with the presence of fluoranthene, a polycyclic aromatic hydrocarbon. Commercially available fluoranthene was positive in the so-called "taped-plate assay" (the test system used for the detection of volatile mutagens) towards the strains TA98 and TA100 in the presence of S9 mix. The tested creosote and coal tar contained fluoranthene in concentrations of 5.2 and 2.2%, respectively.

Coal Tar↗

Detection of benzo[a]pyrene-diol-epoxide-DNA adducts in white blood cells of psoriatic patients treated with coal tar.

An enzyme-linked immunosorbent assay (ELISA) was used to detect BPDE-DNA adducts in white blood cells of 23 psoriatic patients undergoing clinical coal tar therapy. Ten of these patients were reanalyzed 2-5 months after the end of the coal tar treatments. The results show that the mean adduct level during the treatment period was 0.26 +/- 0.16 fmole BPDE/micrograms DNA (7.7 +/- 4.9 adducts/10(8) nucleotides), while 2-5 months later the mean adduct level had decreased significantly (P less than 0.005) to 0.11 +/- 0.08 fmole BPDE/micrograms DNA (3.3 +/- 2.4 adducts/10(8) nucleotides). No relationship could be ascertained between the level of exposure and the amount of BPDE-DNA adducts. In addition, no difference in the level of DNA adducts was found between smoking and non-smoking patients.

Adult↗

UVABA therapy for psoriasis. Efficacy with shortened treatment times with the combined use of coal tar, anthralin, and metal halide ultraviolet machines.

Rapid clearing of psoriasis in a psoriasis treatment center setting has been obtained with a combination of short-contact coal tar, phototherapy from high-pressure metal halide lamps (consisting of UVA and UVB), and short-contact high-potency anthralin therapy. These intensive 1 1/2- to 2-hour treatment sessions done three or four times weekly were as efficacious as reported responses to PUVA therapy or conventional psoriasis day care therapy. The treatment schedule allows minimal time away from work, decreased hours per week in contact with crude coal tar, shortened UV treatment times, decreased cost, and a low risk of side effects. It is suggested that the use of UVA and UVB combined with anthralin (UVABA) is effective for many patients with moderate to severe psoriasis.

Adolescent↗

Evaluation of the dermal carcinogenic potential of tar sands bitumen-derived liquids.

The carcinogenic potential of Athabasca tar sands and six experimental liquids derived from crude bitumen was evaluated utilizing the mouse epidermal carcinogenesis model. Tar sands, bitumen, and untreated naphtha produced few, if any, tumors. Three thermally and catalytically cracked liquids, light (nominal boiling range: 149-316 degrees C) and heavy (nominal boiling range: greater than 316 degrees C) gas oils and gas oil blend (boiling range: greater than 316 degrees C), produced a significant number of epidermal neoplasms. A synthetic crude oil, prepared by blending naphtha and light and heavy gas oils, was moderately carcinogenic; however, the activity of this sample fell within the range of values obtained in studies of crude petroleum samples. Since the bitumen-derived streams do not differ substantially in carcinogenic potency from petroleum-derived materials of comparable boiling range and process history, industrial hygiene practices which limit exposures to levels comparable to those observed in the petroleum-refining industry should provide similar measures of protection.

Animals↗

Smoker intake from cigarettes in the 1-mg Federal Trade Commission tar class.

Cigarette yields measured by the standard analytical procedures of the U.S. Federal Trade Commission (FTC) may not be sufficiently informative to smokers of low-yield brands because actual intake is likely to depend mainly on the aggressiveness of personal behavior. This study determined intake in smokers of 1-mg FTC tar class cigarettes, as they switched brands. Plasma cotinine levels, used as a marker of intake, spanned over a similar range of values from nondetectable to about 800 ng/ml in all brands tested. Pharmacokinetic considerations suggest that smokers of these brands--as a group--intake nicotine in excess of posted FTC values. However, mean values across smokers for each brand, as well as the brand differences in individual smokers, were closely proportional to the analytical differences of FTC nicotine yields for each brand smoked. Thus, standard analytical values may not predict absolute intake of smoke, but they appear to inform about the relative intake smokers can expect from different brands in the 1-mg FTC tar class.

Adult↗

Gas chromatographic-mass spectrometric analysis of tar compounds formed during pyrolysis of rice husks.

Pyrolysis of agricultural waste to produce fuel gas involves formation of tars as noxious by-products. In this paper the qualitative analysis of tars formed during pyrolysis of rice husks is presented, based on identification by gas chromatography-mass spectrometry and interpolation of retention times on a polyaromatic hydrocarbon index scale. The influence of some reaction parameters on product formation is briefly discussed.

Gas Chromatography-Mass Spectrometry↗

Bioremediation of polycyclic aromatic hydrocarbons (PAH) in an aged coal-tar-contaminated soil using different in-vessel composting approaches.

The biodegradation of 16 USEPA-listed PAHs (SigmaPAHs) during simulated in-vessel composting-bioremediation of an aged coal-tar-contaminated soil amended with fresh green waste compost (FGWC) collected from two landfill sites in the United Kingdom (UK) were studied over 56 days. The experimental design compared three constant temperature profiles (TC=38, 55 and 70 degrees C) with one variable temperature profile including treatment at 70 degrees C to comply with regulatory requirements (TP1). The highest disappearance of SigmaPAHs was observed in the soil amended with FGWC (53.2% and 48.1% SigmaPAHs disappearance in soil amended with FGWC-Site 1 and FGWC-Site 2, respectively) containing lower initial organic mater (TOM) (Initial TOM(FGWC-Site 1)=25.6+/-0.6%<Initial TOM(FGWC-Site 2)=32.5+/-0.1%). Compared with previous investigations, higher disappearance of SigmaPAHs occurred when the same coal-tar soil was amended with fresh green waste (56.0% SigmaPAHs disappearance in soil amended with fresh green waste) instead of FGWC. Using a constant TC1=38 degrees C resulted in a higher disappearance of SigmaPAHs when compared to other temperature treatments. However, using a variable temperature profile TP1 during in-vessel composting of a soil amended with fresh green waste is required to promote contaminant degradation and pathogen control.

Bioreactors↗

Using a battery of bioassays, benthic phytoplankton and the AUSRIVAS method to monitor long-term coal tar contaminated sediment in the Cache la Poudre River, Colorado.

This survey provides information on sediment toxicity and structural characteristics of the macroinvertebrates and benthic phytoplankton at 10 locations in the Cache la Poudre River after long-term exposure to coal tar residue. The application of the Australian river bioassessment system (AUSRIVAS) as well as a biotest battery was used to evaluate the river 'health' condition. Coal tar is a dense nonaqueous-phase liquid of significant environmental concern due to its toxicity and persistence in the subsurface. Organisms like Selenastrum capricornutum, Daphnia magna and Chironomus tentans, representing different complexities in the biosphere, were selected as test systems for ecotoxicological studies. The results obtained in this study indicate that a biotest battery, macroinvertebrate and benthic phytoplankton communities are in principle suitable biological tools for evaluation of toxic oil and coal-derived substances in long-term contaminated river sediment.

Animals↗

Synthesis of suspected carcinogenic metabolites of 7H-benzo[c]fluorene, a coal tar component implicated in causation of lung tumors.

High incidences of lung tumors were observed in mice fed coal tar in their diet. The principal component of tar that gives rise to DNA-bound adducts in mouse lung was identified as 7H-benzo[c]fluorene (BcF). We now report the synthesis of suspected active metabolites of BcF, specifically the trans-3,4-dihydrodiol of BcF (2), its likely proximate carcinogenic metabolite, and the corresponding anti- and syn-diol epoxides of BcF (3 and 4) in which the epoxide ring resides in the pseudobay region. The diol epoxide derivatives (3 and 4) are postulated to be ultimate carcinogenic metabolites of BcF that bind to DNA in mouse lung.

Animals↗

Pharmacological coal tar induces G:C to T:A transversion mutations in the skin of muta mouse.

Coal tar is a by-product of the distillation of coal. It consists of a complex chemical mixture of aromatic and aliphatic hydrocabons, with high concentrations of polycyclic aromatic hydrocarbons such as benzo[a]pyrene. We have previously shown that single painting on skin of mice increases the mutation frequency 16 times in murine epidermis cells (Thein et al. 2000). Here, we have determined the mutations by DNA sequencing. Coal tar was found to primarily induce G:C to T:A transversions and one-base pair deletions of G:C base pairs. More than half of the mutations were at CpG sites. The mutational spectrum is in agreement with that of benzo[a]pyrene and other polycyclic aromatic hydrocarbon mixtures.

Animals↗