Reanalysis of the DEMS Nested Case‐Control Study of Lung Cancer and Diesel Exhaust: Suitability for Quantitative Risk Assessment

Crump, Kenny S.; Landingham, Cynthia Van; Moolgavkar, Suresh H.; McClellan, R.O.

doi:10.1111/risa.12371

Cited by 23 publications

(59 citation statements)

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“…We adapted these topics to our present review of studies on DE and lung cancer. In view of the comprehensive discussion about weaknesses in the exposure assessment including the development of alternative approaches (Crump 2006;Hesterberg et al 2006;Gamble 2010;Boffetta 2012a;Crump & Van Landingham 2012;Gamble et al 2012;Crump et al 2015;HEI 2015), we have elected not to discuss this issue in the present review. Any future QRA should proof the robustness of the study results with respect to exposure assessment.…”

Section: Criteria For the Methodological Evaluationmentioning

confidence: 99%

“…However, DE-exposure is influenced by various factors such as weather conditions, type of vehicle/machine and engine, fuel additives, traffic density, and ventilation. The weaknesses of the exposure assessment in the various DE studies assessing lung cancer risk have already been discussed in depth (Crump 2006;Hesterberg et al 2006;Gamble 2010;Boffetta 2012a;Crump & Van Landingham 2012;Gamble et al 2012;Crump et al 2015Crump et al , 2016HEI 2015).…”

Section: Introductionmentioning

confidence: 99%

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A critical review of the relationship between occupational exposure to diesel emissions and lung cancer risk

Möhner

Wendt

2017

Critical Reviews in Toxicology

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In 2012, a working group of the International Agency for Research on Cancer classified diesel exhaust (DE) as a human carcinogen (Group 1). This decision was primarily based on the findings of the Diesel Exhaust in Miners Study (DEMS). The disparity between the results of various methodological approaches applied to the DEMS led to several critical commentaries. An expert panel was subsequently set up by the Health Effects Institute to evaluate the DEMS results, together with a large study in the trucking industry. The panel concluded that both studies provided a useful basis for quantitative risk assessments (QRAs) of DE exposure. However, the results of both studies were non-definitive as the studies suffer from several methodological shortcomings. We conducted a critical review of the studies used by the International Agency for Research on Cancer (IARC) working group to evaluate the relationship between DE and lung cancer. The aim was to assess whether the available studies support the statement of a causal relationship and, secondarily if they could be used for QRA. Our review highlights several methodological flaws in the studies, amongst them overadjustment bias, selection bias, and confounding bias. The conclusion from our review is that the currently published studies provide little evidence for a definite causal link between DE exposure and lung cancer risk. Based on two studies in miners, the DEMS and the German Potash Miners study, QRA may be conducted. However, the DEMS data should be reanalyzed in advance to avoid bias that affects the presently published risk estimates.

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Section: Criteria For the Methodological Evaluationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A critical review of the relationship between occupational exposure to diesel emissions and lung cancer risk

Möhner

Wendt

2017

Critical Reviews in Toxicology

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“…Ergebnisse zur DEMS-Reanalyse wurden in einem HEI (Health Effects Institute) Webinar präsentiert [12,22] …”

Section: Einfluss Der Gewählten Inputdatenunclassified

“…2:[15], modifiziert), so ermittelt die Analyse einen Schwellenwert bei 150 µg/m 3 . Die Schwelle ist aber nicht statistisch signifikant von Null verschieden.Tab 12. Gemeinsame Analyse von Garshick et al[15] (modifizierte Koeffizienten), Silverman et al[36] und Möhner et al[21] (adaptiert) Vergleich der Schätzung der Wirkung für die kumulierte Exposition auf log RR, ermittelt mit unterschiedlichen Regressionsverfahren.…”

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“…Ein solcher Zugriff auf die Originaldaten der DEMS-Studie wurde bislang nur wenigen Forschern ermöglicht (Arbeitsgruppen um S. Moolgavkar und K. Crump), wobei derzeit unklar bleibt, ob diese Autoren uneingeschränkten Zugang zu allen Originaldaten hatten. Die Ergebnisse zur DEMS-Reanalyse wurden in dem HEI (Health Effects Institute) Webinar präsentiert [12,21] und nach Peer-review in "Risk Analysis" zur Publikation angenommen [13,22].…”

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Dieselmotoremissionen und Lungenkrebsrisiken

Morfeld

Spallek

2015

Zbl Arbeitsmed

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Vermeulen et al. [44] publizierten eine Meta-Regressionsanalyse zu 3 wesentlichen epidemiologischen US-amerikanischen Studien [15,36,39], die den Zusammenhang zwischen Dieselmotoremissionen (DME, engl. DEE) -gemessen in der kumulierten Exposition gegenüber elementarem Kohlenstoff (EC) in µg/m 3 -Jahre -und der Lungenkrebsmortalität darstellten. Die Autoren beschreiben, dass einige von ihnen als Mitglieder der IARC-Working Group tätig waren [4], die 2012 ein Review und eine Neubewertung zur karzinogenen Wirkung von DME erstellte ("hazard assessment") und zur Einstufung von DME als Humankanzerogen führte (IARC Group 1). Vermeulen et al. [44] möchten mit dieser Folgearbeit die Überlegungen weiterführen und einen Beitrag zur quantitativen Risikoschätzung ("risk assessment") auf Basis der wesentlichen Studien leisten. Die Autoren ermittelten aus den Daten der 3 Studien als Hauptergebnis eine gemeinsame Expositions-Risiko-Kurve ohne Schwellenwert und folgerten: "We estimated a ln RR of 0,00098 (95 % CI 0,00055-0,0014) for lung cancer mortality with each 1-µg/ m 3 -year increase in cumulative EC based on a linear meta-regression model. Corresponding ln RRs for the individual studies ranged from 0,00061 to 0,0012. Estimated numbers of excess lung cancer deaths through 80 years of age for lifetime occupational exposures of 1, 10, and 25 µg/m 3 EC were 17, 200, and 689 per 10,000, respectively. For lifetime environmental exposure to 0.8 µg/m 3 EC, we estimated 21 excess lung cancer deaths per 10,000. (…) Our estimates suggest that stringent occupational and environmental standards for DEE should be set." Die Arbeit beschreibt somit erhöhte Krebsrisiken selbst bei sehr niedrigen DME-Belastungen. Der Arbeit von Vermeulen et al. [44] wird daher in den laufenden DME-Grenzwertdiskussionen eine wichtige Rolle zukommen. Das US-amerikanische National Institute for Occupational Health (NIOSH) hat nach seiner üblichen Vorgehensweise (Exzessfallberechnung) bereits eine Ableitung versucht [32]: Der Autor ermittelte auf Basis von Vermeulen et al. [44] eine Schät-zung für den 8-h-Grenzwert für DME am Arbeitsplatz von 0,59 µg/m 3 . Da diese Grenzwertableitung deutlich niedriger liegt als beispielsweise die Empfehlung von 100 µg/m 3 DEEE ("diesel engine exhaust emissions"), gemessen als "elemental carbon", des ACSH der EU [42] und der SHEcan-Arbeitsgruppe [9], ist eine kritische Auseinandersetzung mit der Meta-Regressionsanalyse von Vermeulen et al. [44] angezeigt. Material Vermeulen et al. 2014: Inputdaten zur Hauptanalyse ("Primary") Die Basisdaten der Metaanalysen von Vermeulen [mittlere Expositionsschät-zung jeder Expositionskategorie der eingeschlossenen Studien und jeweils zugehöriges relatives Risiko (RR) mit 95 % Konfidenzintervall] sind im Supplement von Vermeulen et al. [44] weitgehend enthalten. Diese Daten wurden extrahiert und in eine Stata-Datei übernommen. Lü-cken wurden gefüllt, soweit die fehlenden Angaben in den Originalpublikationen der Einzelstudien enthalten waren. Als Beispiel zeigt . Tab. 1 die Grunddaten, die in d...

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Diesel Engine Emissions

Greim

2023

Patty's Toxicology

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Emissions from Diesel engines contain several hundred chemical compounds, which are emitted partly as gas and partly as particles. The composition of Diesel exhaust and its concentrations in air have changed significantly over time, to the extent that now there is a distinction between “traditional” and “new technology” diesel emissions. This is important to recognize when evaluating epidemiology studies. New technology Diesel engines comply with emissions from EURO 3 vehicles and higher. Starting with EURO 5 a significant further reduction of particle emissions has been achieved by increased temperature, which however lead to increased emissions of NO x and exceeded the NO 2 emission limit. To overcome this problem some car manufacturers installed illegal software that detected the vehicle test bench operation, resulting in low emissions during the test cycle. Detection of such devices in 2015 led to the “Diesel scandal.” In 2017 the worldwide harmonized light vehicles test procedure (WLTP) was introduced for new cars, which simulates emissions under different driving conditions. It became mandatory for certification of all new vehicles by September 2018. In addition, fleet CO 2 emissions have been introduced for all cars, requiring that by 2020 95% of each manufacturer's passenger car must meet the CO 2 emission target of 95 mg/km, by 2021 100% of the fleet. All these regulations significantly reduced the emissions of Diesel and gasoline‐driven cars, which since the introduction of the EURO 6 regulation in 2014 are almost similar for both. Since the energy efficiency of Diesel motors is up to 20% higher than that of gasoline‐driven cars resulting in up to 20% lower CO 2 emission there is no reason to question the future use of Diesel engines. These regulations apply for new cars and sampling points close to streets with high traffic still exceed the limit values especially for NO 2 . In several cities, this led to restrictions for passenger cars of EURO 5 and below. Since concentrations close to streets are not relevant to evaluate the long‐term exposure of the population these measures are highly debatable. This chapter reviews the toxicology of Diesel exhaust and current regulatory requirements.

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Reanalysis of the DEMS Nested Case‐Control Study of Lung Cancer and Diesel Exhaust: Suitability for Quantitative Risk Assessment

Cited by 23 publications

References 29 publications

A critical review of the relationship between occupational exposure to diesel emissions and lung cancer risk

A critical review of the relationship between occupational exposure to diesel emissions and lung cancer risk

Dieselmotoremissionen und Lungenkrebsrisiken

Diesel Engine Emissions

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