TOXICOLOGICAL PROFILE FOR NONYLPHENOL September 2009 Integrated Risk Assessment Branch Office of Environmental Health Hazard Assessment California Environmental Protection Agency Toxicological Profile for Nonylphenol September 2009 Prepared by Office of Environmental Health Hazard Assessment Prepared for Ocean Protection Council Under an Interagency Agreement, Number 07-055, with the State Coastal Conservancy LIST OF CONTRIBUTORS Authors Jim Carlisle, D.V.M., Ph.D., Senior Toxicologist, Integrated Risk Assessment Branch David Chan, D.Env., Staff Toxicologist, Integrated Risk Assessment Branch Page Painter, M.D., Ph.D., Senior Toxicologist, Integrated Risk Assessment Branch Lily Wu, Ph.D., Associate Toxicologist, Reproductive and Cancer Hazard Assessment Branch Reviewers David Siegel, Ph.D., Chief, Integrated Risk Assessment Branch i Table of Contents Executive Summary ..................................................................................................................... iv Use and Exposure .................................................................................................................... iv Environmental Occurrence ...................................................................................................... iv Effects on Aquatic Life ........................................................................................................... iv Health Hazard and Toxicity in Humans and Laboratory Animals ........................................... v Abbreviations ............................................................................................................................. vii Introduction .................................................................................................................................. 1 Properties and Uses ...................................................................................................................... 1 Environmental Criteria and Contamination .................................................................................. 2 Environmental Fate, Transport, and Bio-uptake .......................................................................... 3 Toxicology: Marine and Other Aquatic Organisms .................................................................... 5 Reproductive and Developmental Toxicity .............................................................................. 5 Vitellogenin (VTG) Assay in Fish ....................................................................................... 5 Other Reproductive Endpoints in Fish ................................................................................. 6 Reproductive Effects on Invertebrates ................................................................................. 7 Other Types of Toxicity ........................................................................................................... 8 Other Toxicity in Fish .......................................................................................................... 8 Other Toxicity in Invertebrates ............................................................................................ 9 Summary and Aquatic Hazard Assessment .............................................................................. 9 Animal and Human Human Studies ............................................................................................. 9 Reproductive Toxicity .............................................................................................................. 9 Introduction .......................................................................................................................... 9 Laboratory Animal Studies ................................................................................................. 10 In Vitro Human Cell-Line Study ........................................................................................ 12 Summary ............................................................................................................................. 12 Developmental Toxicity ......................................................................................................... 12 Introduction ........................................................................................................................ 12 Laboratory Rodent Studies ................................................................................................. 13 Avian Studies ...................................................................................................................... 14 Human Studies .................................................................................................................... 14 Summary ............................................................................................................................. 14 Cancer ..................................................................................................................................... 14 Introduction ........................................................................................................................ 14 Laboratory Rodent Studies ................................................................................................. 15 Effects on Cultured Cells .................................................................................................... 15 Summary ............................................................................................................................. 15 Obesity .................................................................................................................................... 15 Introduction ........................................................................................................................ 15 Laboratory Studies .............................................................................................................. 15 Summary ............................................................................................................................. 16 Thyroid ................................................................................................................................... 16 Introduction ........................................................................................................................ 16 Laboratory Studies .............................................................................................................. 17 Summary ............................................................................................................................. 18 Immune System ...................................................................................................................... 18 ii Introduction ........................................................................................................................ 18 Laboratory Animal Studies ................................................................................................. 18 In Vitro Studies ................................................................................................................... 19 Summary ............................................................................................................................. 20 Nervous System ...................................................................................................................... 20 Introduction ........................................................................................................................ 20 In Vitro Studies ................................................................................................................... 20 Dopaminergic System ........................................................................................................ 21 Summary ............................................................................................................................. 22 Conclusions ................................................................................................................................ 23 Findings .................................................................................................................................. 23 Data Gaps ............................................................................................................................... 24 Recommendations .................................................................................................................. 24 References .................................................................................................................................. 25 Appendix 1: Effects of nonylphenol on aquatic organisms ....................................................... 37 iii Executive Summary This toxicological profile on nonylphenol (NP) describes its effects freshwater and marine life, humans, and laboratory animals. In recent years, NP and related chemical forms of NP have raised concerns because of their effects on the endocrine system, the organ system producing hormones that regulates many of the body's functions. Such concerns have led to many restrictions on the use of NPs within the European Union. Use and Exposure NP is a synthetic organic chemical produced in relatively large quantities in the United States. Primary uses include: (1) a building block of nonionic surfactants (i.e., agents that reduce surface tension of liquids) used in lubrication, defoaming agents, scouring fibers, emulsifiers, wetting