Bitumen products alter bax, bcl‐2 and cytokeratin expression: An in vivo study of chronically exposed road pavers

Loreto, Carla; Rapisarda, Venerando; Carnazza, Maria Luisa; Musumeci, Giuseppe; D’Agata, Velia; Valentino, Matteo; Martinez, G

doi:10.1111/j.1600-0560.2006.00687.x

Cited by 12 publications

(15 citation statements)

References 25 publications

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“…Sixteen non‐smoking male Caucasian road pavers examined in a previous study were recruited 17 . The control group was also the same as in the previous investigation.…”

Section: Methodsmentioning

confidence: 99%

“…Punch skin biopsies 3‐mm diameter were collected from the forearm of all subjects. Sections 3–4 μm in thickness were obtained according to routine procedures, as described previously 17 …”

Section: Methodsmentioning

confidence: 99%

“…Urine samples collected from each subject at the end of an 8‐h shift were analyzed as described previously 17 …”

Section: Methodsmentioning

confidence: 99%

“…In a previous investigation, we showed the activation of apoptosis‐regulating proteins BAX and BCL‐2 in road pavers chronically exposed to bitumen fumes 17 . These molecules play a central role in activation of programmed cell death by the intrinsic pathway 18,19 …”

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confidence: 95%

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Bitumen products induce skin cell apoptosis in chronically exposed road pavers

et al. 2009

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“…Sixteen non‐smoking male Caucasian road pavers examined in a previous study were recruited 17 . The control group was also the same as in the previous investigation.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Urine samples collected from each subject at the end of an 8‐h shift were analyzed as described previously 17 …”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 95%

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Bitumen products induce skin cell apoptosis in chronically exposed road pavers

et al. 2009

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“…Chemical characterization of the paving bitumen was not reported. Results of the biopsies demonstrated statistically significant (p < .05) changes such as upregulation of heat-shock protein 27 (HSP 27) a cellular mechanism that protects against stress factors in inflammatory disease (Fenga et al 2000), overexpression of cytokeratin protein, and BAX (a pro-apoptotic peptide) and under expression of BEL-2 (an anti-apoptotic peptide), all components of an intrinsic pathway of apoptosis (Loreto et al 2007). From the same specimens, Rapisarda et al 2009 identified statistically significant overexpression of components of an extrinsic pathway of apoptosis, the tumor necrosis factor related apoptosis inducing ligand [TRAIL] and its death receptor [DR5], caspase-3, and enhancement of terminal deoxynuceleotidyl transferasemediated dUTP nick ending labeling [TUNEL].…”

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 bei der Heißverarbeitung) [MAK value documentation in German language, 2019]

Hartwig

Arand

2019

The MAK‐Collection for Occupational Health and Safety

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The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the classification of bitumen [ 8052‐42‐4 ; 64741‐56‐6 ; 64742‐93‐4 ] in Carcinogen Category 2 considering all toxicological endpoints. New data allowed a separate assessment of the harmful properties of vapours and aerosols from high‐temperature processing of two bitumen groups. Straight‐Run and Air‐Rectified Bitumen For the derivation of a maximum concentration at the workplace (MAK value), a 2‐year inhalation study in rats exposed to vapours and aerosols from a mixture of straight‐run and air‐rectified bitumen is used. Due to an increased incidence of bronchioalveolar hyperplasia in the lungs and of inflammatory cells in the nasal epithelium, the study resulted in a NOAEC of 6 mg/m 3 . Taking into account the extrapolation from an animal study and the increased respiratory volume at the workplace compared with the exposure of the animals at rest, a MAK value of 1.5 mg/m 3 (sum of vapour and inhalable fraction) is derived for straight‐run and air‐rectified bitumen based on bitumen condensate standard. The MAK value is one‐third of the mean concentration at which three out of 12 inflammation markers are elevated in the sputum of exposed workers. However, the clinical relevance of this finding is unclear and the margin to the MAK value is considered sufficient. The effects on the lung is the most sensitive endpoint, so vapours and aerosols of bitumen are assigned to Peak Limitation Category II with an excursion factor of 2. All in all, the investigated straight‐run and air‐rectified bitumens did not exhibit distinct genotoxic or carcinogenic properties. However, due to the wide range in the chemical composition, harmful emissions of carcinogenic and mutagenic substances during high‐temperature processing cannot be completely excluded. Therefore, vapours and aerosols of straight‐run and air‐rectified bitumens, as commonly used in road paving, are regarded as suspicious carcinogens and classified in Carcinogen Category 3 B. As no data are available for developmental toxicity they are assigned to Pregnancy Risk Group D. Skin contact may contribute significantly to systemic toxicity and the “H” notation is confirmed. Sensitization is not expected from the available data. Oxidized Bitumen There are no inhalation studies available for evaluation of the carcinogenicity of oxidized bitumen (“Roofing Bitumen”). The new animal studies published since 2001 and most of the previous studies show the carcinogenicity of condensates of vapours and aerosols of oxidized bitumens in skin painting studies in mice, so that a significant number of tested oxidized bitumens must be considered carcinogenic. The positive animal experiments on the carcinogenicity are consistent with the results of a genotoxicity study in roofing workers with increased DNA strand break rates. Vapours and aerosols of oxidized bitumen are classified in Carcinogen Category 2. A MAK value could not be derived. Mutations in bacteria and higher levels of benzo[a]pyrene in oxidized bitumen condensates compared to those of straight‐run and air‐rectified bitumen and the systemic availability of inhaled vapours and aerosols of oxidized bitumen support suspicion of germ cell mutagenicity. Therefore, vapours and aerosols of oxidized bitumen are classified in Category 3 B for germ cell mutagens. Skin contact may contribute significantly to systemic toxicity and the “H” notation is confirmed. Sensitization is not expected from the available data.

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Bitumen products alter bax, bcl‐2 and cytokeratin expression: An in vivo study of chronically exposed road pavers

Abstract: Overexpression of the cytokeratin pattern and bax and underexpression of bcl-2 in chronically bitumen-exposed skin suggest that bitumen fumes induce activation of apoptosis as a defense mechanism.

Cited by 12 publications

References 25 publications

Bitumen products induce skin cell apoptosis in chronically exposed road pavers

Bitumen products induce skin cell apoptosis in chronically exposed road pavers

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

Bitumen (Dampf und Aerosol bei der Heißverarbeitung) [MAK value documentation in German language, 2019]

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