Toxicological Review and Recommended Toxicological Reference Values for Environmental Lead Exposure in Canada Prepared for: Health Canada Healthy Environments and Consumer Safety Branch Safe Environments Directorate Environmental Health Bureau Contaminated Sites Division Ottawa, ON Prepared by: Norm Healey, Azimuth Consulting Group Inc. (formerly with Health Canada) Heather Jones-Otazo, Health Canada Mike Walker, Health Canada Anthony Knafla, Equilibrium Environmental Inc. March, 2010 T OXICOLOGICAL R EVIEW AND R ECOMMENDED TRVS F OR E NVIRONMENTAL L EAD E XPOSURE IN C ANADA Note to Readers Units The SI units for the concentration of lead in blood are µmol/L. Most studies, however, report blood lead concentrations in units of µg/dL. By convention, blood lead concentrations are presented in this report in units of µg/dL. To convert blood lead concentrations in µg/dL to µmol/L, divide by 20.72. i This report was prepared under contract to Health Canada's Contaminated Sites Division; however, this report does not necessarily reflect the opinion of Health Canada nor is it Health Canada guidance. T OXICOLOGICAL R EVIEW AND R ECOMMENDED TRVS F OR E NVIRONMENTAL L EAD E XPOSURE IN C ANADA Authorship & History of this Report Norm Healey is the first author and overall editor of this report. Heather Jones-Otazo researched and authored the review of epidemiological evidence of the carcinogenic effects of lead. Mike Walker used literature reported cancer bioassay data to conduct cancer dose- response modeling and calculate quantitative estimates of cancer potency. Anthony Knafla is the first author of a contract report on the toxicology of lead that was previously commissioned by Health Canada (Equilibrium Environmental Inc., 2008a). The review of the toxicological literature on lead in this report is based partly on Equilibrium Environmental Inc.( 2008a) and Anthony Knafla is the first author of the analysis of population health effects associated with a decrement in mean IQ of one point and an increase in mean systolic blood pressure of 1.3 mmHg (Appendix A). The first draft of this report (December 2008) was compiled and subject to international peer review while Norm Healey was employed by Health Canada. Norm Healey resigned from Health Canada and began working for Azimuth Consulting Group Inc. (Azimuth) in February 2009. Azimuth, under subcontract to Equilibrium Environmental Inc., was contracted during the 2009-2010 fiscal year to update the December 2008 draft report in response to referee comments. Suggested citation: Healey, N., H. Jones-Otazo, M. Walker, A. Knafla. 2010. Toxicological Review and Recommended Toxicological Reference Values for Lead Exposure in Canada. Report prepared for Health Canada, Healthy Environments and Consumer Safety Branch, Environmental Health Bureau, Ottawa, ON. ii T OXICOLOGICAL R EVIEW AND R ECOMMENDED TRVS F OR E NVIRONMENTAL L EAD E XPOSURE IN C ANADA As per direction from Health Canada (Mark Richardson, Chief, Contaminated Sites Division) publisher permissions were not required for reproduction of figures presented in this report, owing to the fact that the document is to serve as a Health Canada internal report. iii T OXICOLOGICAL R EVIEW AND R ECOMMENDED TRVS F OR E NVIRONMENTAL L EAD E XPOSURE IN C ANADA ACKNOWLEDGEMENTS A draft version of this report was peer reviewed by: Dr. Ellen Silbergeld, Johns Hopkins University, USA Dr. David Bellinger Harvard University, USA Dr. Mary Jean Brown, Center for Diseases Control, USA Dr. Bruce Lanphear, University of British Columbia, Canada Dr. Lisa Chiodo, Wayne State University, USA Dr. Esben Budtz-Joergensen, University of Copenhagen, Denmark Dr. Glyn R. Fox, British Columbia Ministry of the Environment, Canada Dr. Barbara S. Glen, U.S. Environmental Protection Agency, USA Ms. Josephine Archbold, Toronto Public Health, Canada Dr. Lesbia Smith, Environmental & Occupational Health Plus Inc. Canada Dr. Kenny S. Crump, Louisiana Tech, USA Dr. Mei-Tein Lo, Health Canada, Canada Mr. Mark Feeley, Health Canada, Canada Dr. Ana Navas-Acien, Johns Hopkins Bloomberg School of Public Health, USA Dr. Paul Mushak, PB Associates, USA Mr. Mark Payne, Public Health, York Region, Canada Dr. Deborah C. Rice, Maine Center for Disease Control, USA Dr. Ted Lidsky, New York State Institute for Basic Research in Developmental Disabilities, USA Dr. N. D. Vaziri, University of California, Irvine, USA Dr. Tim Nawrot, Universiteit Hasselt, Belgium Mr. Kyle Wivcharuk, Region of Peel, ON, Canada Mr. Ross Wilson, Wilson Scientific Inc., Vancouver, BC, Canada These referees provided many constructive comments that improved the final draft of this report, but they were not asked to endorse the conclusions or recommendations of this report nor did they review the final draft of the report. iv T OXICOLOGICAL R EVIEW AND R ECOMMENDED TRVS F OR E NVIRONMENTAL L EAD E XPOSURE IN C ANADA The following research scientists gave generously of their time to answer questions from the report authors or to provide information or data that was required for this report but was not included in their published papers: Dr. Bruce Lanphear, Simon Fraser University Dr. Richard Hornung, Cincinnati Children's Hospital Medical Center Dr. David Bellinger, Harvard School of Public Health Dr. Suma Vupputuri, Kaiser Permanente (formerly NIEHS) Dr. Lisa Chiodo, Wayne State University Dr. Deborah C. Rice, Maine Center for Disease Control (formerly Health Canada) Dr. Deborah Cory-Slechta, University of Rochester Dr. Gunnar Nordberg, University of Umea, Umea, Sweden Dr. Michael P. Waalkes, National Cancer Institute at National Institute of Environmental Health Sciences, USA Health Canada, with the support of consulting scientists, has been working on the review of its toxicological reference values for lead since 2004. Over the past five years a great number of people have contributed to the ideas and data that are presented in this report. The efforts and contributions of the following individuals are gratefully acknowledged: Dr. Mark Richardson, Health Canada Ms Kimberly Brewer, Health Canada Ms. Chun Lei Liang, Health Canada Mr. Mike Inskip, Health Canada Ms. Reva Berman, Health Canada Mr. Paul Walters, Health Canada v T OXICOLOGICAL R EVIEW AND R ECOMMENDED TRVS F OR E NVIRONMENTAL L EAD E XPOSURE IN C ANADA Ms. Shairoz Ramji, Health Canda Ms. Sanya Petrovic, Health Canada Ms. Elizabeth Hardacre and the other library staff at the Health Canada, Healthy Environments Consumer Safety Branch, BC Regional and National libraries Ms. Pamela Olson and the other library staff at the Institute of Ocean Sciences, Fisheries and Oceans Canada Dr. Hans Damman, Fisheries and Oceans Canada Ms. Jillian Carey, Equilibrium Environmental Inc. The members of: Health Canada Lead Workng Group Health Canada Interdepartmental Lead Issues Working Group The referees of: Equilibrium Environmental Inc. (2008a). Critical Review of Potential Health Effects Associated with Lead (Pb). Health Canada, Healthy Environment and Consumer Safety Branch, Safe Environments Programme, Contaminated Sites Division, Burnaby, BC. Report No. HECS-SEP-BC/Yukon 05-06-22 Mr. Ross Wilson, Wilson Scientific Inc. Dr. Lesbia Smith, Environmental & Occupational Health Plus Inc. Dr. Angella Li-Muller, Health Canada Ms. Mary Ellen Starodub, Starodub Associates Inc. Dr. Michele Joffres, Simon Fraser University vi T OXICOLOGICAL R EVIEW AND R ECOMMENDED TRVS F OR E NVIRONMENTAL L EAD E XPOSURE IN C ANADA Dr. David Chettle, McMaster University Dr. David Fleming, Mount Allison University Dr. Mei-Tein Lo, Health Canada The peer collaborators and referees of: Equilibrium Environmental Inc. (2008b). Lead (Pb) Toxicokinetic Modeling in Support of the Development of a Toxicity Reference Value. Health Canada, Healthy Environment and Consumer Safety Branch, Safe Environments Programme, Contaminated Sites Division, Burnaby, BC. Dr. David Chettle, McMaster University Dr. David Fleming, Mount Allison University Mr. Sean Hayes, Summit Toxicology Inc. Dr. Paul Mushak, PB Associates Inc. Dr. Deborah C. Rice, Maine Center for Disease Control Dr. Fiona McNeill, McMaster University Dr. Ron Brecher, Globaltox Inc. Mr. Mike Inskip, Health Canada The authors and referees of: Cantox Environmental Inc., Environmental and Occupational Health +Plus and GlobalTox International Consultants (2006). Update of Evidence for Low-Level Effects of Lead and Blood Lead Intervention Levels. Health Canada, Healthy Environment and Consumer Safety Branch, Safe Environments Programme, Toxic Substances Division, Ottawa, ON. vii T OXICOLOGICAL R EVIEW AND R ECOMMENDED TRVS F OR E NVIRONMENTAL L EAD E XPOSURE IN C ANADA Extended Summary Introduction This report presents a critical review of the evidence of the toxicological effects of lead (Pb) and recommends toxicological reference values (TRVs) for primary prevention of adverse population health effects from environmental lead exposure in Canada. The lead TRVs presented in this report are not intended to define the maximum amount of environmental lead exposure that is tolerable or acceptable. The lead TRVs presented in this report are points of reference to help risk assessors quantify the potential health risks associated with a given lead exposure scenario and describe the associated uncertainty. Whether or not the potential health risks are tolerable or acceptable is a value judgement that is within the purview of risk managers and stakeholders. This report has three general parts: (1) an overview of the diverse systemic toxic effects of lead and a comparison