Formation of DNA Adducts in Skin, Lung and Lymphocytes After Skin Painting of Rats with Undiluted Bitumen or Coal-Tar Fume Condensates

Genevois, C; Brandt, H.; Bartsch, Helmut; Obrecht-Pflumio, Sophie; Wild, Christopher P.; Castegnaro, M.

doi:10.1080/10406639608048337

Cited by 25 publications

(20 citation statements)

References 18 publications

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“…In order to compare the data from the inhalation study with those of the previously performed skin-painting study using the BD4 ratstrain, a skin application was performed on one rat of the specific pathogen-free BD6 strain, using condensates prepared from the same bitumen (45/60 pen) heated at 200°C as described in Genevois et al [9].…”

Section: Rat Exposure By Skin-paintingmentioning

confidence: 99%

“…These batches were used for the production of the fume condensates [8,9,12]. In the inhalation study, only the Venezuelan batch of bitumen and the coal-tar were used.…”

Section: Products Tested and Conditionsmentioning

confidence: 99%

“…The skin-painting of rats with these BFCs, or with similar amounts of CTFCs as positive controls, led to DNA adduct formation in lungs, skin and lymphocytes [9], the patterns of DNA adducts formed by BFCs being completely different from those formed by CTFCs.…”

mentioning

confidence: 98%

“…In order to identify possible biomarkers of exposure to bitumen fumes, IARC has performed a number of studies, comprising in vitro DNA adduct formation [8], in vivo skin-painting [9] and an inhalation study [lo, 111. For the first two studies we generated fume condensates that are representative of the fumes to which workers are exposed in the field and demonstrated that bitumen fume condensates (BFCs) and, as reference, coal-tar fume condensates (CTFCs) generated in the same way, are mutagenic in the Ames test and induce the formation of DNA adducts in vitro and in vivo [8,9].…”

mentioning

confidence: 99%

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Inhalation Study on Exposure to Bitumen Fumes: Formation of DNA Adducts in Various Rat Tissues Following Nose-only Inhalation

Genevois-charmeau

Binet

Bonnet

et al. 2001

Polycyclic Aromatic Compounds

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During the hot application of bitumen containing materials, e.g., in hot paving or roofing, fumes are emitted that contain traces of polycyclic aromatic compounds (PACs) including heterocyclic and/or substituted PACs. Previous studies of DNA adduct formation by bitumen and coal-tar fume condensates (BFCs and CTFCs, respectively) indicated that the genotoxic compounds responsible for DNA adduct formation in BFCs and CTFCs were of different nature. Moreover, it was suggested that the major adduct found in the lungs and also in skin and lymphocytes of BFC-treated rats might be usable as a marker of exposure to bitumen fumes.In the present study, we compared the genotoxic activity of inhaled bitumen and coaltar fumes generated under controlled conditions as measured by the formation of DNA adducts. Rats were exposed for 6 hours/day on 5 days, to bitumen and coal-tar fumes by nose-only. At concentration of 5 mg/m3 particulate matter in the inhalation chamber, neither bitumen fumes nor coal-tar fumes produced detectable levels of adducts in any of the tissues analysed (lungs, liver, kidneys and lymphocytes). The absence of DNA adducts in the 5 mg/m3 bitumen and the 5 mg/m3 coal-tar inhalation experiments is possibly due to low dose of inhaled PACs. These levels were probably below a threshold dose necessary for the formation of detectable adducts. To confirm this hypothesis, a 50 mg/m3 total particulate matter (TPM) level bitumen fume inhalation experiment was performed. The quantitative composition of the fumes at 50mg/m3 differed from that at the 5 mg/m3 level and, the 50mg/m3 was not considered to be representative of fumes to which workers are exposed in the field. Notwithstanding those quantitative differences in fume composition it was felt that these fumes could be used for the qualitative detection of DNA adducts in this inhalation study. At this level of particulate matter, a DNA adduct was detected only in the lungs of the three exposed rats. This adduct had similar chromatographic properties to the major one detected in the lungs of rats treated by skin-painting with the BFCs.Further experimental and epidemiological research is needed to characterise this DNA adduct and to use it as a possible marker for exposure to fumes from bitumen.

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Section: Rat Exposure By Skin-paintingmentioning

confidence: 99%

“…These batches were used for the production of the fume condensates [8,9,12]. In the inhalation study, only the Venezuelan batch of bitumen and the coal-tar were used.…”

Section: Products Tested and Conditionsmentioning

confidence: 99%

mentioning

confidence: 98%

mentioning

confidence: 99%

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Inhalation Study on Exposure to Bitumen Fumes: Formation of DNA Adducts in Various Rat Tissues Following Nose-only Inhalation

Genevois-charmeau

Binet

Bonnet

et al. 2001

Polycyclic Aromatic Compounds

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“…Genevois et al 1996Genevois et al , 1998 explored this activity in adduct formation with calf thymus DNA and skin painting of rats with bitumen fume condensate collected at 160 or 200 C from Venezuelan 45/60 pen. CYP1A isoforms and aryl hydrocarbon receptor (AHR) both played important roles in PAC activation, although CYP1A2 played a lesser role than CYP1A1.…”

Section: Mechanistic Studiesmentioning

confidence: 99%

Assessing cancer hazards of bitumen emissions – a case study for complex petroleum substances

Kriech¹,

Schreiner²,

Osborn³

et al. 2017

Critical Reviews in Toxicology

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When assessing cancer hazard and risk associated with a complex petroleum substance, like bitumen emissions, there are often conflicting results related to human, animal and mechanistic studies. Validation of the complex composition to assure that it matches real-world exposures and control of confounders are pivotal factors in study design to allow the necessary read-across during assessments. Several key studies on bitumen emissions in two-year dermal cancer assays reported variable outcomes ranging from high cancer incidence to no cancer incidence. Here, we synthesize findings from published studies to explain the differences and discuss critical factors in cancer hazard evaluation for complex petroleum substances. Using these critical factors, we reviewed relevant human genetic toxicity, mammalian toxicity and mechanistic studies with bitumen to understand the divergence in results. We assess the most reliable and scientifically supported information on the potential carcinogenic hazards of bitumen emissions and comment on quality and completeness of data. Human hazard data are typically considered highest priority because they eliminate the need for interspecies extrapolation and reduce the range of high -to low-dose extrapolation during the risk assessment process. Finally, two well-conducted comprehensive animal studies are discussed that have well-defined test material, exposure concentration and composition representative of worker exposure, evidence of systemic uptake, no confounding exposures and provide consistency across all elements within both studies. Studies that allow effective read-across from human, animal and mechanistic components, control for confounders and are well-validated analytically against workplace exposures, provide the strongest evidence base for evaluating cancer hazard. ARTICLE HISTORY

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Bitumen (Dampf und Aerosol) [MAK Value Documentation in German language, 2001]

2012

The MAK‐Collection for Occupational Health and Safety

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Veröffentlicht in der Reihe Gesundheitsschädliche Arbeitsstoffe , 32. Lieferung, Ausgabe 2001 Der Artikel enthält folgende Kapitel: Zusammensetzung und Analytik Allgemeiner Wirkungscharakter Wirkungsmechanismus Toxikokinetik und Metabolismus Erfahrungen beim Menschen Einmalige Exposition Wiederholte Exposition Wirkung auf Haut und Schleimhäute Allergene Wirkung Reproduktionstoxizität Genotoxizität Kanzerogenität Tierexperimentelle Befunde und In‐vitro‐Untersuchungen Akute Toxizität Subakute, subchronische und chronische Toxizität Wirkung auf Haut und Schleimhäute Allergene Wirkung Reproduktionstoxizität Gentoxizität Kanzerogenität Sonstige Wirkungen Bewertung

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Formation of DNA Adducts in Skin, Lung and Lymphocytes After Skin Painting of Rats with Undiluted Bitumen or Coal-Tar Fume Condensates

Cited by 25 publications

References 18 publications

Inhalation Study on Exposure to Bitumen Fumes: Formation of DNA Adducts in Various Rat Tissues Following Nose-only Inhalation

Inhalation Study on Exposure to Bitumen Fumes: Formation of DNA Adducts in Various Rat Tissues Following Nose-only Inhalation

Assessing cancer hazards of bitumen emissions – a case study for complex petroleum substances

Bitumen (Dampf und Aerosol) [MAK Value Documentation in German language, 2001]

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