Bijdrage Van Nieuwe Epidemiologische Studies Aan De .
Bijdrage van nieuwe epidemiologischestudies aan de onderbouwing van declassificatie van dieselmotoremissies alshumaan carcinogeenRoel Vermeulen, PhDIRAS, Environmental Epidemiology DivisionUtrecht University, the NetherlandsJulius Center, Health Sciences and Primary CareUniversity Medical Center Utrecht, The NetherlandsCGC December 4
Monograph 105
Outline IARC evaluation process Exposure to diesel engine exhaust (DEE) Human cancer evidence of DEE Evidence available at previous evaluation New epidemiological evidence
“The encyclopaedia of carcinogens”The IARC Monographs evaluate ChemicalsComplex mixturesOccupational exposuresPhysical and biological agentsLifestyle factorsMore than 900 agents have been evaluated 107 are carcinogenic to humans (Group 1) 63 are probably carcinogenic to humans (Group 2A) 271 are possibly carcinogenic to humans (Group 2B)Lorenzo Tomatis1929-2007National and international health agencies use the Monographs As a source of scientific information on known or suspected carcinogens As scientific support for their actions to prevent exposure to known orsuspected carcinogens
IARC Evaluations - Subgroup WorkCancer inhumans Cancer inexperimental animalsSufficient evidenceLimited evidenceInadequate evidenceEvidence suggesting lack ofcarcinogenicity Sufficient evidenceLimited evidenceInadequate evidenceEvidence suggesting lack ofcarcinogenicityMechanistic andother relevant data Mechanistic data “weak,”“moderate,” or “strong”? Mechanism likely to beoperative in humans?Overall evaluation Group 1Carcinogenic to humans Group 2AProbably carcinogenic to humans Group 2BPossibly carcinogenic to humans Group 3Not classifiable as to its carcinogenicity to humans Group 4Probably not carcinogenic to humans
IARC Evaluations – Dimensions and ClassesEVIDENCE IN EXPERIMENTAL ANIMALSSufficientSufficientInadequateESLCGroup 1 (carcinogenic to humans)Group 2ALimitedLimited(probablycarcinogenic)Group 2B (possibly carcinogenic)(exceptionally, Group 2A)EVIDENCEIN HUMANSGroup 2BInadequateESLC(possiblycarcinogenic)Group 3 (not classifiable)Group 4
Mechanistic Data can be Pivotal when theHuman Data are not ConclusiveEVIDENCE IN EXPERIMENTAL oup 1é1 strong evidence in é2A belongs to a mechanistic class where other members areLimitedEVIDENCEIN HUMANSInadequateexposed humansGroup 2Aclassified in Groups 1 or 2AGroup 2B (exceptionally, Group 2A)é1 strong evidence in é2A belongs to aexposed humansmechanistic classmechanistic classé2A strong evidence é2B with supporting é2B with strong mechanism alsooperates in humansGroup 2Bê3 strong evidence evidence frommechanistic andother relevant dataGroup 3mechanism doesnot operate inhumansESLCé2A belongs to aGroup 3evidence frommechanistic andother relevant dataGroup 3Group 3ê4 consistently andstrongly supportedby a broad range ofmechanistic andother relevant dataGroup 4
Overall Evaluation – Vol 105,Diesel Engine Exhaust There is sufficient evidence for the carcinogenicity inhumans of DEE. DEE causes lung cancer. Also, apositive association between DEE and bladder cancerhas been observed. There is sufficient evidence for the carcinogenicity inexperimental animals of whole diesel engine exhaust. Overall evaluationDEE is carcinogenic for humans
Outline IARC evaluation process Exposure to diesel engine exhaust Human cancer evidence of DEE Evidence available at previous evaluation New epidemiological evidence
Exposure to DEE Diesel engines are predominantly used for heavy dutyequipment trains converting to diesel locomotive mainly after World War heavy-duty trucks dieselized primarily during the mid and late1950s. Occupational exposure prevalence (ever) European Union: 12 million workers North America: 12 million workers
ge DE Exposure Levels (EC ug/m3) byOccupational Categories250200150100500
DEE Qualitatively Changes Overtime
DEE Qualitatively Changes OvertimeScheepers and Vermeulen, 2012
Outline IARC evaluation process Exposure to diesel engine exhaust Human cancer evidence of DEE Evidence available at previous evaluation New epidemiological evidence
Previous Human Evidence Moderate increase in risk of lung cancer at levels ofexposure experienced by workers(RR 1.33, 95% 1.24 – 1.44, based on 29 risk estimates; Bhatia et al., 1998) Some evidence of a modest increase in risk of bladdercancer among workers exposed to diesel exhaust(RR 1.1 - 1.3; Boffetta and Silverman, 2001) Inconsistent evidence for multiple myeloma, pancreas,prostate, larynx, kidney cancer
Relative Risks Lung Cancer and Diesel ExposureBhatia et al., 1998
Relative Risks Lung Cancer and Diesel ExposureBhatia et al., 1998
Weaknesses Lack of control for confounding Smoking Insufficient (quantitative) exposure assessment Lack of dose-response within and across occupations
EPICOH 2013 - Utrecht 18 – 21 June 2013
The IARC Monographs evaluate Chemicals Complex mixtures Occupational exposures Physical and biological agents . experimental animals of whole diesel engine exhaust. Overall evaluation DEE is carcinogenic for humans . Outline IARC evaluation process Exposure to diesel engine exhaust
naar een 'nieuwe' marker bij triple-negatieve borstkankercellen. Als eenmaal een 'nieuwe' marker inclusief bijbehorend gen is gevonden, onderzoekt Luuk de rol van dit gen bij de ontwikkeling van kanker met behulp van knock-out muizen. Uiteindelijk hoopt Luuk een nieuwe behandelmethode 'op maat' te vinden voor deze groep patiënten.
De bijdrage van ICT tot energie-efficiëntie: Lokale en regionale initiatieven . Dat is de rol van deze toolkit. Aangezien ICT reeds alomtegenwoordig zijn en alom gebruikt worden, is energie-efficiëntie in vele gevallen niet de belangrijkste nagestreefde doelstelling; dankzij verder inzicht in de .
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overeenkomst in de vraagstelling van de auteurs en de verscheidenheid in de uit-werking daarvan hebben een rijke bijdrage opgeleverd die kan worden aange-wend om de status van de publieke dimensie van kennis opnieuw te bepalen. Als voorbereiding op dit wrr-rapport zijn tevens twee studies verricht naar de rol van ict in het onderwijs.
The Audit and Accounting Thresholds . AAT is a registered charity. No. 1050724. 3. Accounting Threshold The . regulations apply in respect of financial years beginning on or after 1 January 2016 whereby the audit threshold and the accounting threshold have become the same for private limited companies. The requirements for a private limited company that is also a charity are different. Please .
