Studies with Diesel Exhaust Particulate: Implications for the Potential Human Health Hazards of Nanoparticles

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1 Studies with Diesel Exhaust Particulate: Implications for the Potential Human Health Hazards of Nanoparticles Thomas W. Hesterberg, PhD, MBA Director, Product Stewardship, Sustainability, and Environmental Health Navistar, Inc. Chicago, USA Webinar Nanotoxicology Specialty Section Society of Toxicology December 14, 2011

2 Introduction At early stages of assessing human health risks of nanoparticles Animal and in vitro studies of nanoparticles Substantial uncertainties May not be relevant to humans Nanoparticles are a major constituent of diesel exhaust Many animal inhalation and human epidemiology studies of DE over last 30 years More recent human volunteer exposure studies 2

3 Diesel Exhaust Particles 3

4 Traditional Diesel Exhaust (TDE) Exhaust from engines utilizing old technologies: Pre-1988 diesel engines sold and in use prior to the US EPA diesel particulate standards Transitional diesel engines Progressive improvements in engine design, but Prior to the full-scale implementation of multi-component after-treatment systems 4

5 Diesel Particle Size Distribution 5

6 Occupational Exposures to Diesel PM Exposure Group DPM (ug/m 3 ) Ambient < 4 Truckers 10 Railroad works 70 Surface miners 88 Underground miners 830 6

7 Lung Cancer in Railroad Workers Small elevation in lung cancer risk, but cause is uncertain Cancer risk does not increase with exposure or duration of employment Lack of exposure measurements Possible confounding from cigarette smoking 7

8 Lung Cancer in Truck Drivers No change in lung cancer risk after truck dieselization 8

9 Lung Cancer in Underground Miners Despite underground miners having the highest occupational exposures to diesel exhaust, no change in lung cancer risk 9

10 Chronic Animal Studies of Diesel Exhaust and Carcinogenicity No tumors observed in mice or hamsters Tumors in rats only at very high exposures(1,000 ug/m 3 ) Thought to be non-specific response to lung overload Seen with inert dusts, e.g., talc, TiO 2, carbon black, that are not in the nanoparticle size range Lung overload-related tumors not observed in humans, even in coal miners exposed to overload levels of coal dust Inflammation and other lung effects observed were similar to what is seen with larger particles, e.g. amorphous silica 10

11 Lung Tumor Excess in Rats Seen Only Above Lung Overload Exposures Threshold for Lung Overload

12 Mutagenicity Studies Diesel particulate matter contains mutagenic compounds, but Mutagenic compounds are not bioavailable Explains why tumors not seen in animal studies, except above overload levels in rats Whole diesel exhaust not likely to be mutagenic 12

13 Summary Diesel Exhaust Lung Cancer Studies Human workplace studies show small increase in lung cancer, but no exposure-response demonstrated Miners, who have highest DE exposures show no increase in lung cancer Lung cancer not found in mice or hamsters and only at very high lung overload exposures in rats No unusual toxicity noted in the lungs of animals exposed chronically to diesel exhaust nanoparticles (Hesterberg et al. Critical Reviews in Toxicology 36: , 2006) 13

14 Human Volunteer Exposures to TDE Reviewed 30 human volunteer studies Studies used exposure chambers Allows control and precise measurement of exposure conditions Exposed 2-3 hours to diesel exhaust Studies performed in UK, Sweden, and USA Traditional Diesel Exhaust (TDE) engines Many used 20 year old diesel engine No exhaust after treatment which has been required since 2007 (Hesterberg et al. Inhalation Toxicology 22(8): , 2010) 14

15 Some Caveats Diesel exhaust (DE) exposure also contains: Larger-sized particles in the fine range Gases: carbon monoxide, nitrogen dioxide, nitric acid, carbon dioxide Volatile organic compounds Other nanoparticles (NPs) may have properties different diesel exhaust NPs DE particles may be less toxic than other nanoparticles 15

16 Controlled and Ambient Exposure to Diesel Particulate Matter Controlled diesel exposures 5 to 10 times higher than ambient exposures 16

17 Controlled and Ambient Exposure to Diesel Particles 17

18 Workplace Nanoparticles vs. DE Studies CNT Handling Metal Oxide Handling CNT Machining Metal Oxide Reactor Cleanout 18

19 Lung Function 19

20 Lung Inflammation 20

21 Lung Inflammation and Blood Clotting 21

22 Cardiovascular System ET-1) 22

23 Diesel Exhaust Studies and NP Toxicity High diesel exhaust nanoparticle exposures may elicit transient, subclinical effects in human volunteers Effects generally less or not seen at lower exposure levels Responses similar to those observed with larger particles These studies do not provide evidence of a unique toxicity of nanoparticles compared to larger particles Hesterberg et al. Inhalation Toxicology 22(8): ,

24 Evolution of US Heavy Duty Diesel On-Road Emission Standards 1994 Fuel Sulfur PPM (10/93) NOx [g/bhp-hr] (NTDE) 2002 FUEL SULFUR ULSD 15 PPM (10/06) (NTDE) PM [g/bhp-hr] 24

25 New Technology Diesel Exhaust (NTDE) Exhaust from engines utilizing new technologies: Meets EPA & CARB 2007 emissions standards Fully integrated electronic control systems Ultra low sulfur diesel fuel (< 15 ppm) Oxidation catalysts Wall-flow diesel particulate filters (DPFs) Applies to both new and retrofitted engines 25

26 Key to Emissions Reductions in NTDE Wall-flow Diesel Particulate Filter Trapped PM Cell Plugs Exhaust (CO2, H2O) Out Exhaust (PM, CO, HC) Enter Reductions: 95+% PM 80 to 100% HC, CO 80 to 99+% toxins Porous Ceramic Wall Adapted from MECA,

27 NTDE: Lower Particulate Emissions TDE Percent of TDE NTDE Veh1-baseline Veh1-DPF1 Veh1-DPF1+SCR1 Veh1-DPF1+SCR2 Veh2-DPF2 Veh3-DPF3 Veh4-DPF4 CARB Study: Herner et al., EST 43: , 2009, data from Table 2. Transit Buses: UDDS Test Cycle 27

28 Most Toxic Air Contaminants (TACs) in TDE are Not Found in NTDE Others Reduced to Near-Zero Levels Aniline Antimony compounds Arsenic Beryllium compounds Cadmium Chlorine (chloride) Chlorobenzene and derivatives Chromium compounds Cobalt compounds Ethylbenzene Inorganic lead Manganese Mercury 4-Nitrobiphenyl Nickel Selenium Styrene Xylene isomers and mixtures o-xylenes p-xylenes m-xylenes Ullman et al, SAE ,

29 NTDE Reduces Emissions Across a Broad Spectrum of Compounds Category Reduction Relative to TDE Single Ring Aromatics 82% PAH 79% Alkanes 85% Hopanes/Steranes 99% Alcohols & Organic Acids 81% Nitro-PAHs 81% Carbonyls 98% Inorganic Ions 71% Metals & Elements 98% Organic Carbon 96% Elemental Carbon 99% Dioxins/Furans 99% Khalek et al., JAWMA

30 Percent TDE PM Composition and Mass Comparisons TDE NTDE PM Mass CNG OC EC Sulfate Nitrate Lev-On et al., SAE , Transit Bus TDE NTDE CNG 30

31 PM Composition and Mass Comparisons Percent of TDE TDE PM Mass NTDE OC EC Gasoline WSOC Nitrate Cheung et al., Env. Sc. Tech. 43: , Passenger TDE NTDE Gasoline 31

32 Percent of TDE NTDE: Lower Regulated Emissions Also Similar or Better than CNG or Gasoline NTDE CNG Gasoline TDE 0 CO PM NOx HC NMHC CO2 (2010 Std) Hesterberg et al., ES&T 42: ,

33 Recent NTDE Nanoparticle Study In Vitro Test Results Catalytic after-treatment results in higher number of nanoparticles More nanoparticles associated with lower toxicity in DTT and macrophage assays Herner et al. ES&T 45: ,

34 Relative Response Animal Inhalation Study Traditional Diesel Exhaust (TDE) vs New Technology Diesel Exhaust (NTDE) TDE 2.5 NTDE Filtered Air Viral Burden Histopathology Inflammation (TNFa) Oxidative Stress McDonald et al., Env Health Perspectives 112: , 2004, developed from Figures

35 Percent Filtered Air Recent Human Volunteer Studies Traditional Diesel Exhaust (TDE) vs New Technology Diesel Exhaust (NTDE) Ex Vivo Thrombus Formation NTDE gave same response as Filtered Air Acetylcholine Vasodilation TDE NTDE Filtered Air Lucking et al. Circulation 123: ,

36 Research In Progress Advanced Collaborative Emissions Study (ACES) Managed by the Health Effects Institute Funded by government agencies and industry Lifespan inhalation study in rodents Lung disease and cancer are main endpoints Two more years to complete 36

37 Summary on NTDE vs TDE PM levels in NTDE are 100-fold lower than in TDE NTDE PM is chemically very different from TDE Similar to CNG and gasoline PM NTDE emissions generally lower than CNG or gasoline Biological effects of TDE were not observed with NTDE NTDE should be evaluated separately from TDE Hesterberg et al, JAWMA, 61: ,

38 NTDE and NP Toxicity High diesel exhaust nanoparticle exposures may elicit transient, subclinical effects in human volunteers Effects generally less or not seen at lower exposure levels Responses similar to those observed with larger particles Effects not observed with New Technology Diesel Exhaust These studies do not provide evidence of a unique toxicity of nanoparticles compared to larger particles Hesterberg et al., Inhalation Toxicology 22(8): , Hesterberg et al., JAWMA, 61: ,