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Estimation of the Exposure-Response Relation between Benzene and Acute Myeloid Leukemia by Combining Epidemiologic, Human Biomarker, and Animal Data

Scholten, B. (author), Portengen, L. (author), Pronk, A. (author), Stierum, R. (author), Downward, G.S. (author), Vlaanderen, J. (author), Vermeulen, R. (author)

Background: Chemical risk assessment can benefit from integrating data across multiple evidence bases, especially in exposure–response curve (ERC) modeling when data across the exposure range are sparse. Methods: We estimated the ERC for benzene and acute myeloid leukemia (AML), by fitting linear and spline-based Bayesian meta-regression models...

article 2022

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Automated Network Assembly of Mechanistic Literature for Informed Evidence Identification to Support Cancer Risk Assessment

Krishnan, S. (author), Vermeulen, R. (author), Pronk, A. (author), Gyori, B.M. (author), Bachman, J.A. (author), Vlaanderen, J. (author), Stierum, R. (author)

BACKGROUND: Mechanistic data is increasingly used in hazard identification of chemicals. However, the volume of data is large, challenging the efficient identification and clustering of relevant data. OBJECTIVES: We investigated whether evidence identification for hazard assessment can become more efficient and informed through an automated...

article 2022

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Thin Functional Zeolite Layer Supported on Infrared Resonant Nano-Antennas for the Detection of Benzene Traces

Nuñez, J. (author), Boersma, A. (author), Grand, J. (author), Mintova, S. (author), Sciacca, B. (author)

Infrared absorption spectroscopy is a powerful analytical tool that enables the identification of molecular species. The sensitivity of this technique, that is strongly limited by the small absorption cross-section of molecular vibration, can be greatly improved by resonant interaction with nano-antennas via the surface-enhanced infrared...

article 2021

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A Quantitative Meta-Analysis of the Relation between Occupational Benzene Exposure and Biomarkers of Cytogenetic Damage

Scholten, B. (author), Vlaanderen, J. (author), Stierum, R. (author), Portengen, L. (author), Rothman, N. (author), Lan, Q. (author), Pronk, A. (author), Vermeulen, R. (author)

BACKGROUND: The genotoxicity of benzene has been investigated in dozens of biomonitoring studies, mainly by studying (classical) chromosomal aberrations (CAs) or micronuclei (MN) as markers of DNA damage. Both have been shown to be predictive of future cancer risk in cohort studies and could, therefore, potentially be used for risk assessment of...

article 2020

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Neurobehavioral effects of acute exposure to aromatic hydrocarbons

McKee, R.H. (author), Lammers, J.H.C.M. (author), Muijser, H. (author), Owen, D.E. (author), Kulig, B.M. (author), TNO Kwaliteit van Leven (author)

This article reports the results of neurobehavioral tests on representative aromatic constituents, specifically C₉ to C₁₁ species. The testing evaluated effects in several domains including clinical effects, motor activity, functional observations, and visual discrimination performance. Exposures ranging from 600 to 5000 mg...

article 2010

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Isolation and characterization of Alicycliphilus denitrificans strain BC, which grows on benzene with chlorate as the electron acceptor

Weelink, S.A.B. (author), Tan, N.C.G. (author), ten Broeke, H. (author), van den Kieboom, C. (author), van Doesburg, W. (author), Langenhoff, A.A.M. (author), Gerritse, J. (author), Junca, H. (author), Stams, A.J.M. (author), TNO Bouw en Ondergrond (author)

A bacterium, strain BC, was isolated from a benzene-degrading chlorate-reducing enrichment culture. Strain BC degrades benzene in conjunction with chlorate reduction. Cells of strain BC are short rods that are 0.6 μm wide and 1 to 2 μm long, are motile, and stain gram negative. Strain BC grows on benzene and some other aromatic compounds with...

article 2008

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A physiologically based biokinetic (PBBK) model for estragole bioactivation and detoxification in rat

Punt, A. (author), Freidig, A.P. (author), Delatour, T. (author), Scholz, G. (author), Boersma, M.G. (author), Schilter, B. (author), van Bladeren, P.J. (author), Rietjens, I.M.C.M. (author), TNO Kwaliteit van Leven (author)

The present study defines a physiologically based biokinetic (PBBK) model for the alkenylbenzene estragole in rat based on in vitro metabolic parameters determined using relevant tissue fractions, in silico derived partition coefficients, and physiological parameters derived from the literature. The model consists of eight compartments including...

article 2008

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Model studies for evaluating the neurobehavioral effects of complex hydrocarbon solvents. III. PBPK modeling of white spirit constituents as a tool for integrating animal and human test data

Hissink, A.M. (author), Krüse, J. (author), Kulig, B.M. (author), Verwei, M. (author), Muijser, H. (author), Salmon, F. (author), Leenheers, L.H. (author), Owen, D.E. (author), Lammers, J.H.C.M. (author), Freidig, A.P. (author), McKee, R.H. (author), TNO Kwaliteit van Leven (author)

As part of a project designed to develop a framework for extrapolating acute central nervous system (CNS) effects of hydrocarbon solvents in animals to humans, experimental studies were conducted in rats and human volunteers in which acute CNS effects were measured and toxicokinetic data were collected. A complex hydrocarbon solvent, white...

article 2007

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Human cytochrome P450 enzyme specificity for the bioactivation of estragole and related alkenylbenzenes

Jeurissen, S.M.F. (author), Punt, A. (author), Boersma, M.G. (author), Bogaards, J.J.P. (author), Fiamegos, Y.C. (author), Schilter, B. (author), van Bladeren, P.J. (author), Cnubben, N.H.P. (author), Rietjens, I.M.C.M. (author), TNO Kwaliteit van Leven (author)

Human cytochrome P450 enzymes involved in the bioactivation of estragole to its proximate carcinogen 1′-hydroxyestragole were identified and compared to the enzymes of importance for 1′-hydroxylation of the related alkenylbenzenes methyleugenol and safrole. Incubations with Supersomes revealed that all enzymes tested, except P450 2C8, are...

article 2007

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Evidence for large average concentrations of the nitrate radical (NO3) in Western Europe from the HANSA hydrocarbon database

Penkett, S.A. (author), Burgess, R.A. (author), Coe, H. (author), Coll, I. (author), Hov, O. (author), Lindskog, A. (author), Schmidbauer, N. (author), Solberg, S. (author), Roemer, M. (author), Thijsse, T. (author), Beck, J. (author), Reeves, C.E. (author), TNO Bouw en Ondergrond (author)

The nitrate radical (NO3) was first measured in the atmosphere in the 1970s and suggestions were made that it could play a major role in oxidising many unsaturated hydrocarbons, such as those emitted from the biosphere. Analysis of the hydrocarbon mix over the North Atlantic Ocean suggested subsequently that the influence of NO3 radical...

article 2007

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Physiological and phylogenetic characterization of a stable benzene-degrading, chlorate-reducing microbial community

Weelink, S.A.B. (author), Tan, N.C.G. (author), ten Broeke, H. (author), van Doesburg, W. (author), Langenhoff, A.A.M. (author), Gerritse, J. (author), Stams, A.J.M. (author), TNO Bouw en Ondergrond (author)

A stable anoxic enrichment culture was obtained that degraded benzene with chlorate as an electron acceptor. The benzene degradation rate was 1.65 mM benzene per day, which is similar to reported aerobic benzene degradation rates but 20-1650 times higher than reported for anaerobic benzene degradation. Denaturing gradient gel electrophoresis of...

article 2007

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Transcriptomics analysis of interactive effects of benzene, trichloroethylene and methyl mercury within binary and ternary mixtures on the liver and kidney following subchronic exposure in the rat

Hendriksen, P.J.M. (author), Freidig, A.P. (author), Jonker, D. (author), Thissen, U. (author), Bogaards, J.J.P. (author), Mumtaz, M.M. (author), Groten, J.P. (author), Stierum, R.H. (author), TNO Kwaliteit van Leven (author)

The present research aimed to study the interaction of three chemicals, methyl mercury, benzene and trichloroethylene, on mRNA expression alterations in rat liver and kidney measured by microarray analysis. These compounds were selected based on presumed different modes of action. The chemicals were administered daily for 14 days at the Lowest...

article 2007

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Quantum chemistry based quantitative structure-activity relationships for modeling the (sub)acute toxicity of substituted mononitrobenzenes in aquatic systems

Zvinavashe, E. (author), Murk, A.J. (author), Vervoort, J. (author), Soffers, A.E.M.F. (author), Freidig, A. (author), Rietjens, I.M.C.M. (author), TNO Kwaliteit van Leven (author)

Fifteen experimental literature data sets on the acute toxicity of substituted nitrobenzenes to algae (Scenedesmus obliquus, Chlorella pyrenoidosa, C. vulgaris), daphnids (Daphnia magna, D. carinata), fish (Cyprinus carpio, Poecilia reticulata), protozoa (Tetrahymena pyriformis), bacteria (Phosphobacterium phosphoreum), and yeast (Saccharomyces...

article 2006

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Toxicogenomic analysis of gene expression changes in rat liver after a 28-day oral benzene exposure

Heijne, W.H.M. (author), Jonker, D. (author), Stierum, R.H. (author), van Ommen, B. (author), Groten, J.P. (author), TNO Kwaliteit van Leven (author)

Benzene is an industrial chemical, component of automobile exhaust and cigarette smoke. After hepatic bioactivation benzene induces bone marrow, blood and hepatic toxicity. Using a toxicogenomics approach this study analysed the effects of benzene at three dose levels on gene expression in the liver after 28 daily doses. NMR based metabolomics...

article 2005

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Characterization of some synthetic Ru and Ir complexes by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

Lou, X. (author), van Buijtenen, J. (author), Bastiaansen, J.J.A.M. (author), de Waal, B.F.M. (author), Langeveld, B.M.W. (author), van Dongen, J.L.J. (author), TNO Industrie en Techniek (author)

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) was applied to the analysis of Ru(OCOCF 3)2(CO)(PPh3)2, Ru(OCOC 3F7)2(CO)(PPh3)2, Ir(tBuppy)3 and Ir(ppy)2(acac) complexes. A troublesome problem in the MALDI-TOFMS characterization of these metal complexes is the possible replacement of complex ligands by...

article 2005

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Dermal exposure assessment to benzene and toluene using charcoal cloth pads

van Wendel de Joode, B. (author), Tielemans, E. (author), Vermeulen, R. (author), Wegh, H. (author), Kromhout, H. (author), TNO Kwaliteit van Leven (author)

Charcoal cloth pads have been used to assess volatile chemicals on the skin in a laboratory setting; however, they have not yet been applied to measure dermal exposure in occupational settings. This study aimed at evaluating whether charcoal pads can be used to assess dermal exposure to benzene and toluene in workers of a petrochemical plant....

article 2005

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Exposure to combinations of substances: A system for assessing health risks

Feron, V.J. (author), van Vliet, P.W. (author), Notten, W.R.F. (author), TNO Voeding (author)

Combined exposures may be categorised as specified combinations or mixtures of substances, depending on composition and exposure scenario. The major characteristic of a specified combination is known composition and that of a mixture simultaneous exposure. A framework was developed as a guide for safety evaluation of combined exposures. This...

article 2004

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Differential susceptibility of rats and guinea pigs to the ototoxic effects of ethyl benzene

Cappaert, N.L.M. (author), Klis, S.F.L. (author), Muijser, H. (author), Kulig, B.M. (author), Ravensberg, L.C. (author), Smoorenburg, G.F. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

The present study was designed to compare the ototoxic effects of volatile ethyl benzene in guinea pigs and rats. Rats showed deteriorated auditory thresholds in the mid-frequency range, based on electrocochleography, after 550-ppm ethyl benzene (8 h/day, 5 days). Outer hair cell (OHC) loss was found in the corresponding cochlear regions. In...

article 2002

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Health risks associated with inhaled nasal toxicants

Feron, V.J. (author), Arts, J.H.E. (author), Kuper, C.F. (author), Slootweg, P.J. (author), Woutersen, R.A. (author)

Health risks of inhaled nasal toxicants were reviewed with emphasis on chemically induced nasal lesions in humans, sensory irritation, olfactory and trigeminal nerve toxicity, nasal immunopathology and carcinogenesis, nasal responses to chemical mixtures, in vitro models, and nasal dosimetry- and metabolism-based extrapolation of nasal data in...

article 2001

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Simultaneous exposure to ethyl benzene and noise: Synergistic effects on outer hair cells

Cappaert, N.L.M. (author), Klis, S.F.L. (author), Muijser, H. (author), Kulig, B.M. (author), Smoorenburg, G.F. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

The effects on hearing of simultaneous exposure to the ototoxic organic solvent ethyl benzene and broad-band noise were evaluated in rats. The effects of three ethyl benzene concentrations (0, 300 or 400 ppm) and three noise levels (95 or 105 dBlin SPL or background noise at 65 dBlin SPL) and all their combinations were investigated for a 5 day...

article 2001