Review Effects of phthalates on the development and expression of allergic disease and asthma Michelle L. North, PhD * , y, jj ; Tim K. Takaro, MD, MPH, MSc, FACOEM z ; Miriam L. Diamond, MSc, MScEng, PhD x ; and Anne K. Ellis, MD, MSc, FRCPC, FAAAAI * , y, jj * Department of Biomedical and Molecular Sciences, Queen’s University, Kingston, Ontario, Canada y Allergy Research Unit, Kingston General Hospital, Kingston, Ontario, Canada z Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada x Department of Earth Sciences, University of Toronto, Toronto, Ontario, Canada jj Division of Allergy and Immunology, Department of Medicine, Queen’s University, Kingston, Ontario, Canada A R T IC L E IN F O Article history: Received for publication November 16, 2013. Received in revised form February 7, 2014. Accepted for publication March 21, 2014. A B ST R AC T Objectives: To review recent evidence relating phthalate exposures to allergies and asthma and to provide an overview for clinicians interested in the relevance of environmental health research to allergy and who may encounter patients with concerns about phthalates from media reports. Data Sources: PubMed, TOXLINE, and Web of Science were searched using the term phthalate(s) combined with the keywords allergy, asthma, atopy, and inflammation. Study Selection: Articles were selected based on relevance to the goals of this review. Studies that involved humans were prioritized, including routes and levels of exposure, developmental and early-life exposures, immunotoxicity, and the development of allergic disease. Results: The general public and those with allergy are exposed to significant levels of phthalates via diet, pharmaceuticals, phthalate-containing products, and ambient indoor environment via air and dust. Intra- venous exposures occur through medical equipment. Phthalates are metabolized and excreted quickly in the body with metabolites measured in urine. Phthalates, which are known endocrine disrupting compounds, have been associated with oxidative stress and alterations in cytokine expression. Metabolites in human urine, particularly of the higher-molecular-weight phthalates, have been associated with allergies and asthma in multiple studies. Conclusion: Despite mounting evidence implicating phthalates, causation of allergic disease by these com- pounds cannot currently be established. In utero and early-life exposures and possible transgenerational effects are not well understood. However, considering the current evidence, reducing exposures to phthalates by avoiding processed and foods packaged and stored in plastics, personal care products with phthalates, polyvinyl chloride materials indoors, and reducing home dust is advised. Further longitudinal, molecular, and intervention studies are needed to understand the association between phthalates and allergic disease. Ó 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved. Introduction North Americans have widespread exposure to phthalates. 1 An increasing literature documents widespread exposure to phthalates and putative links to adverse health effects. Among those potential links is the development and exacerbation of allergic disease. 1 As more evidence comes to light, practicing allergists may find that they are being asked by patients, or parents of patients, whether chemicals such as phthalates cause allergies and how to avoid them. This article provides some background on phthalates and sources of exposure. We review recent studies that have linked phthalates to allergies and asthma, potential mechanisms of action, and some early research into potential interventions to reduce exposure. The Structure and Uses of Phthalates Phthalates are synthetic diesters of phthalic acid that are used in many consumer and building products. 2,3 Individual phthalate compounds vary in molecular weight and physical-chemical properties according to hydrocarbon chain and branching pattern. The most common phthalates can be loosely grouped into lower molecular weight (dimethyl phthalate [DMP], diethyl phthalate [DEP], and dibutyl phthalate [DBP]), and higher molecular weight (diethyl hexyl phthalate [DEHP], diisononyl phthalate [DINP], dii- sodecyl phthalate [DIDP], and benzyl butyl phthalate [BBP]). These Reprints: Anne K. Ellis, MD, MSc, FRCPC, FAAAAI, Division of Allergy & Immunology, Department of Medicine, Queen’s University, Doran 1, Kingston General Hospital, 76 Stuart St, Kingston, ON K7L 2V7, Canada; E-mail: ellisa@queensu.ca. Disclosures: Authors have nothing to disclose. Contents lists available at ScienceDirect 1081-1206/14/$36.00 - see front matter Ó 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.anai.2014.03.013 Ann Allergy Asthma Immunol xxx (2014) 1e7