COMMUNICATION 9 Evaluation of Human Health Risk from Cerium Added to Diesel Fuel August 2001 Contributors to the Project PROJECT LEADER Maria G Costantini, Senior Scientist, Health Effects Institute ADVISORS Rogene Henderson, Senior Scientist and Deputy Director, National Edo D Pellizzari, Vice President for Analytical and Chemical Environmental Respiratory Center, Lovelace Respiratory Research Sciences, Research Triangle Institute and HEI Review Committee Institute and HEI Research Committee Robert Sawyer, University of California at Berkeley and Chair, HEI Daniel S Greenbaum, President, Health Effects Institute Special Committee on Emerging Technologies Helmut Greim, Professor and Chair of Toxicology, Technical Jane Warren, Director of Science, Health Effects Institute University Munich, GSF–National Research Center for Environment and Health and HEI Research Committee HEI CONTRIBUTORS Martha Richmond, currently at Suffolk University Jenny Lamont, Scientific Copy Editor Sally Edwards, Director of Publications Ruth E Shaw, Senior DTP Specialist OUTSIDE REVIEWERS James Ball, Ford Motor Company John McAughey, AEA Technology, Great Britain Steve Cadle, General Motors Corporation Roger McClellan, Consultant, President Emeritus Chemical J Michael Davis, US Environmental Protection Agency, Industry Institute of Toxicology National Center for Environmental Assessment Robert F Phalen, University of California College of Norbert Englert, Umweltbundesamt, Germany Medicine, Irvine David Kittelson, University of Minnesota Glenn Simon, Rhodia Andreas Mayer, Technik Thermische Maschinen, Switzerland Michael Waalkes, National Cancer Institute The Health Effects Institute thanks Dr Glen Simon and Mr Jacques Lemaire of Rhodia, and Mr Andreas Mayer of Technik Thermische Maschinen for providing many of the reports and papers cited in this document and for clari- fying aspects of the Eolys technology. Evaluation of Human Health Risk from Cerium Added to Diesel Fuel Health Effects Institute Communication 9 August 2001 Copyright © 2001 Health Effects Institute, Boston MA USA. Printed at Flagship Press in North Andover MA. The paper in this publication meets the minimum standard requirements of the ANSI Standard Z39.48-1984 (Permanence of Paper). CONTENTS HEI Communication 9 Abstract . 1 Health Effects of Cerium . 20 Introduction. 2 Acute Toxicity . 21 Cerium Occurrence and Use . 3 Target Organ Effects. 21 Proposed Use. 3 Inhalation Exposure . 21 Characterization of Emissions with Cerium Ingestion Exposure . 22 Additive. 4 Intravenous and Subcutaneous PM Emissions with Additive But No Filter . 4 Administration . 22 PM Emissions with Additive and Filter . 5 Immune Sensitization. 23 Gaseous Emissions with Additive and Filter . 9 Behavioral and Developmental Effects . 23 Discussion . 9 Carcinogenicity and Genotoxicity . 24 Characterization of Exposure to Cerium In Vitro Cellular Effects . 24 from Additive. 10 Macrophages . 24 Cerium Emission Factors . 11 Myocytes . 25 Estimated Cerium Levels in the Biological Molecules . 25 Environment . 11 Discussion . 25 Air . 11 Overall Assessment . 27 Soil. 12 Emission of Cerium . 28 Considerations About Estimated Cerium in Air and Soil . 28 Levels . 12 Fate of Cerium in the Body. 28 Baseline Cerium Levels in the Environment . 12 Health Effects of Cerium. 29 Air . 12 Conclusions. 30 Soil. 12 References . 31 Discussion . 13 Appendix A. Diesel Emissions Standards Deposition and Fate of Cerium in the Body . 14 for PM . 36 Inhalation Exposure. 14 Appendix B. Details About Studies Reported Ingestion Exposure. 18 in Tables 1 Through 5. 39 Intravenous, Intraperitoneal, and Appendix C. Summary Tables of Animal and Subcutaneous Administration. 19 In Vitro Studies . 41 Discussion . 19 Abbreviations and Other Terms. 57 Publishing History: This document was posted as a preprint on www.healtheffects.org and then finalized for print. Citation for whole report: Health Effects Institute, 2001. Evaluation of Human Health Risk from Cerium Added to Diesel Fuel. Communication 9. Health Effects Institute, Boston MA. When specifying a section of this report, cite it as a chapter of this document. HEI COMMUNICATION 9 Evaluation of Human Health Risk from Cerium Added to Diesel Fuel cerium concentrations from its use as a fuel additive sug- ABSTRACT gested that the expected increase could be several orders of The fuel efficiency and durability of diesel technology magnitude (in areas with a high volume of diesel traffic) are particularly desirable in the transportation and con- and that cerium concentrations in soil may double over struction industries. Concerns about the health effects of several decades. Specifically, an ambient cerium concentra- 3 diesel particulate emissions have led to progressively tion of 0.6 µg/m was estimated along a highway and of 3 stricter emission standards, which can be met only 1.25 µg/m in a street canyon; concentrations due to depo- through new technologic advances and fuel modifications. sition of cerium-containing PM in soil were predicted to be The cerium-based fuel additive Eolys*, used in conjunc- 5 to 30 ppm around roads with high traffic by the year 2050. tion with a particulate filter, is one of the approaches being Cerium in the soil may be absorbed into vegetation or may considered. However, this additive will result in emissions contaminate water, but the extent of such contamination of cerium compounds and an increase in cerium in the cannot be estimated. ambient air and soil. HEI developed this report to provide The main routes of exposure of the public to a qualitative assessment of the possible health risk of cerium-containing particles are inhalation and ingestion. cerium used as a fuel additive. Inhaled cerium is cleared from the respiratory tract by A limited number of short-term diesel engine tests different pathways and at different rates depending on its have confirmed that cerium (20 to 100 ppm in the fuel) solubility in body fluids. The clearance pathways used with the particulate filter substantially decreases include: mucociliary clearance to the mouth followed by both particle mass (> 90%) and number (99%) concentra- swallowing and excretion via the feces; translocation to tions in the exhaust. Despite the filter’s high efficiency in the pulmonary and tracheobronchial lymph nodes, and trapping particulate matter (PM), however, a small dissolution and absorption into the systemic circulation amount of cerium is emitted in the particulate phase of and distribution to various organs. Based on a 1978 clas- the exhaust. Cerium measured in emissions was found sification by the National Council on Radiation Protec- primarily in the oxide form and in particles less than 0.5 tion and Measurements (NCRP), relatively insoluble µm in diameter. Cerium mass relative to the total particle cerium compounds (such as hydroxides and oxides) are mass was between 3% and 18% based on two tests using cleared from the lung over a period of years. The more two different types of filters. soluble forms (such as chlorides, phosphates, and nitrates used in many of the experimental studies) are Because cerium is present in soil and is being used in cleared over a period of weeks. Insoluble forms are also some vehicle manufacturing and other industrial processes, less likely than soluble forms to reach the circulation and a baseline level exists in both ambient air and soil. The be deposited in other organs, while a proportionally most recent measurements in the Los Angeles area report greater amount would be found in the lymph nodes. Mod- cerium levels of about 0.5 ng/m3 in fine PM. The average eling of particle (1 µm in diameter) clearance estimated cerium level in the earth’s crust worldwide has been esti- that about 80% of inhaled cerium deposited in the lung mated to be 20 to 60 ppm although higher levels have been would clear through the gastrointestinal tract, about 5% measured in areas with anthropogenic sources of cerium. to 15% would translocate to the systemic circulation, and The one effort to estimate increases in environmental the remainder would translocate to the lymph nodes. Cir- culating cerium deposits primarily in the liver and bones * A list of abbreviations and other terms appears at the end of the Commu- nication. and then is slowly removed. Other organs that may accu- Although this document was produced with partial funding by the United mulate some cerium are spleen, heart, and brain. States Environmental Protection Agency under Assistance Award R828112 to the Health Effects Institute, it has not been subjected to the Agency's peer Cerium taken up by ingestion is excreted in the feces and administrative review and therefore may not necessarily reflect the after transiting in the digestive tract. Studies in rodents fed views of the Agency, and no official endorsement by it should be inferred. The contents of this document also have not been reviewed by private party cerium salts (in relatively soluble forms) showed that less institutions, including those that support the Health Effects Institute; there- than 0.1% of the ingested dose is absorbed by the gas- fore, it may not reflect the views or policies of these parties, and no endorse- ment by them should be inferred. trointestinal tract and distributed to other organs. Health Effects Institute Communication 9 © 2001 1 HEI Communication 9 Literature on the health effects of cerium is limited. concern when inhaled or ingested at the low levels that Inhalation of cerium is of more concern than ingestion would be encountered in