Carcinogenicity of Diesel Exhaust: Old and New Technology Diesel

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1 April 5-7, 2016 Carcinogenicity of Diesel Exhaust: Old and New Technology Diesel Katherine Walker Senior Scientist Health Effects Institute Boston, MA

2 Who is the Health Effects Institute? An independent, nonprofit corporation chartered in 1980 with balanced funding from USEPA and the worldwide motor vehicle industry Commissioned to provide high-quality, impartial, and relevant science on the health effects of air pollutants HEI s goal is simply to gain acceptance by all parties of the data that may be necessary for future regulation. Willam Ruckleshaus, Former EPA Administrator 2

3 Research, Critical Review, Communication Air Pollution Research 3

4 Old v. New Diesel Exhaust ACES 2007, 2010 engines Epidemiologic Studies 4

5 Closing the books on Old diesel exhaust and carcinogenicity 5

6 HEI Diesel Epi Panel Evaluation Charge: Multidisciplinary Panel To review and analyze the newest studies of lung cancer risk in workers exposed to older diesel exhaust and assess their potential for use in quantitative risk assessment (QRA) Chair: Daniel Krewski, Professor and Director McLaughlin Center for Population Health Risk Assessment, University of Ottawa 6

7 New evidence helps tip the balance: International Agency for Research on Cancer 2012 Group 2A: Probably Carcinogenic Group 1: Carcinogenic to Humans 7

8 The Diesel Exhaust in Miners Study: A Cohort Mortality Study with Emphasis on Lung Cancer Attfield et al The Diesel Exhaust in Miners Study: A Nested Case- Control Study of Lung Cancer and Diesel Exhaust Silverman et al T T T S L P P P 8-Non-metal mines 3 potash mines 3 trona (soda ash) mines 1 salt (halite) mine 1 low-silica limestone mine Adapted from D. Silverman presentation 8 Cohort: 12,315 males Diesel marker: Respirable elemental carbon (REC) Historical exposure estimates: ~1947 to 2001 Mortality follow-up: to 1997 Lung cancer cases: 200 Nested Case-Control: 198 cases, 666 matched controls

9 Lung Cancer and Elemental Carbon Exposure in Trucking Industry Workers Garshick et al Cohort: 31, 135 males employed in 1985 Diesel marker: Submicron elemental carbon (SEC) Historical exposure Estimates : Mortality follow-up: to 2000 Lung cancer cases: 779 9

10 A broad range of exposures. 1.7 Measured Annual Average MATES IV EC µg/m

11 DEMS results indicate an exposurerelated increase in lung cancer risk All Subjects: Ever-underground and surface only Odd s Ratio=1.0 (no effect) Silverman et al

12 Truckers results indicate weaker exposure-related response Entire Cohort N= 31,135 Excluding Mechanics N= 29,324 Hazard Ratio=1.0 (no effect) Main Models: Cumulative exposures 5-year lagged Adjusted for duration of work No association with average exposures Garshick et al HR (95% CI) 12

13 Does the evidence hang together? Many assumptions required exposure lags models exposure metrics (REC, SEC, EC) Uncertainties need to be taken into account 13 Vermeulen et al. 2013

14 Overall Panel Conclusions Both studies were well-designed and conducted according to high standards of epidemiological research. The results and data from both the Truckers and the DEMS can be usefully applied in quantitative risk assessments of older diesel engine exhaust. However, QRAs will need to take into account some key uncertainties and limitations. 14

15 What about New Diesel? Advanced Collaborative Emissions Study Emissions Characterization* Tox Studies Phase I Phase 2 Phase 3 4 new HDDEs Meeting 2007 PM Standards 3 new HDDEs meeting 2010 PM standards Health Effects Studies in Rats HDDE randomly chosen Overseen by Coordinated Research Council (CRC), conducted by Imad Khalek,(Southwest Research Institute) 15 Conducted at Lovelace Respiratory Research Institute

16 Phase I and 2: Major declines in PM Mass and Numbers Emissions 16

17 Meet emissions standards by large margins* (FTP cycle, g/bhp-hr) Year PM Measured NO Measured Emissions Standards *Aside light duty VW s also meet the PM emissions standards in on road tests 17

18 Elemental carbon (EC) is no longer 4% 1998 the major component 23% 73% EC 53.1% 2007 PAH s have been reduced by >90-99% 30% 4% 13% 2% 13% 2010 OC EC 1% Elements 2% Sulfate 16% 66% Ammonium Nitrate 18

19 What does this all mean for health? ACES Phase 3: first-ever lifetime animal study of effects of new technology diesel engine emissions (NTDE) 2007 engine, randomly chosen Substantially more rigorous than normal National Toxicology Program cancer tests: 80 hours of exposure per week Tough Engine operating cycle Twice as many animals (200) Exposures up to 30 months 2015 Full Report available at: 19

20 No sign of tumors with NTDE 2007 DE Engine: Mild changes consistent with NO2 exposures, no tumors Old DE engines: High particle loading, tumors 20

21 What are the implications for you? 21

22 Need to focus on where highest exposures occur to which pollutants and to whom? 22

23 Non-cancer mortality (cardiovascular disease) drives benefits estimates ~$1.7 billion for PM alone On/non road diesel play important roles Measuring Clean Air Act Progress: Costs vs. Benefits (Section 812 Prospective Analysis) 23

24 US Burden of Disease: Air pollution remains an important risk factor 13th Lung cancer: ~25% of air pollution deaths, ~1% of deaths from all risk factors. 24 Institute for Health Metrics and Evaluation

25 Deaths per 100,000 Progress: Estimated cancer death rates attributable to air pollution are going down US Burden of Disease : Institute for Health Metrics and Evaluation 25 Year

26 We ve come a long way Los Angeles Beijing, China Thank-you! All our publications are available online at: 26

27 EXTRA SLIDES 27

28 Questions for future quantitative cancer risk analyses What is the observed risk of lung cancer? Risk characterization: modeling, assumptions, adjustments uncertainties: Population demographics Differences in smoking, other risk factors Levels and timing of personal exposures over a lifetime Changes in emission levels and composition (ACES) Real world emissions compliance What is the predicted risk of lung cancer? Image of general population Other relevant data methods, and analyses 28

29 Challenges: DEMS Retrospective exposure assessment REC data : DEMS Survey (dust, EC, OC, gases) at 7/8 mines Validation datasets 1976: MESA Air Monitoring Survey 1994: Feasibility study (Stanevich et al., 1997) Determinants of Exposure : MIDAS mine inspection records (stationary CO, other gases) : Mine ventilation maps : Diesel equipment inventories Diesel trends : Work histories : Diesel begins 1990 s: New engine technology

30 Greater than 90% reduction in PAHs (including known carcinogens) Many PAHs now below detection limits (Khalek et al 2011) Polycyclic Aromatic Hydrocarbons (PAHs), including nitro-pahs, have been of major concern in diesel exhaust Many known to cause cancer Some of the most toxic comds. are so low they can no longer be measured 30

31 Phase 3B Study Design: Rat Exposures to NTDE Expose male and female rats (Wistar Han strain) for a lifetime = 28 months for males, 30 months for females, 16 hr/day, 5 days/wk engine: Three dilutions of whole emissions + clean air controls 4.2 ppm NO 2 = High (filter PM chamber inlet = 12.3 ug/m 3 ) 0.8 ppm NO 2 = Medium (filter PM chamber inlet = 1.07 ug/m 3 ) 0.1 ppm NO 2 = Low (filter PM chamber inlet = 0.3 ug/m 3 ) NO 2, rather than PM, chosen as target pollutant 31 Months after start of exposure (males and females) Assignment and 30 Chronic bioassay (histopathology) Intermediate sacrifice (biologic endpoints) Cumulative total