Estimated daily intake of phthalates in occupationally exposed groups CYNTHIA J. HINES a , NANCY BN. HOPF a , JAMES A. DEDDENS a,b , MANORI J. SILVA c AND ANTONIA M. CALAFAT c a National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Cincinnati, Ohio, USA b Department of Mathematical Sciences, University of Cincinnati, Cincinnati, Ohio, USA c National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA Improved analytical methods for measuring urinary phthalate metabolites have resulted in biomarker-based estimates of phthalate daily intake for the general population, but not for occupationally exposed groups. In 2003–2005, we recruited 156 workers from eight industries where materials containing diethyl phthalate (DEP), dibutyl phthalate (DBP), and/or di(2-ethylhexyl) phthalate (DEHP) were used as part of the worker’s regular job duties. Phthalate metabolite concentrations measured in the workers’ end-shift urine samples were used in a simple pharmacokinetic model to estimate phthalate daily intake. DEHP intake estimates based on three DEHP metabolites combined were 0.6–850 mg/kg/day, with the two highest geometric mean (GM) intakes in polyvinyl chloride (PVC) film manufacturing (17 mg/kg/day) and PVC compounding (12 mg/kg/day). All industries, except phthalate manufacturing, had some workers whose DEHP exposure exceeded the U.S. reference dose (RfD) of 20 mg/kg/day. A few workers also exceeded the DEHP European tolerable daily intake (TDI) of 50 mg/kg/day. DEP intake estimates were 0.5–170 mg/kg/day, with the highest GM in phthalate manufacturing (27 mg/kg/day). DBP intake estimates were 0.1–76 mg/kg/day, with the highest GMs in rubber gasket and in phthalate manufacturing (17 mg/kg/day, each). No DEP or DBP intake estimates exceeded their respective RfDs. The DBP TDI (10 mg/kg/day) was exceeded in three rubber industries and in phthalate manufacturing. These intake estimates are subject to several uncertainties; however, an occupational contribution to phthalate daily intake is clearly indicated in some industries. Journal of Exposure Science and Environmental Epidemiology (2011) 21, 133–141; doi:10.1038/jes.2009.62; published online 16 December 2009 Keywords: phthalates, biomonitoring, personal exposure. Introduction Phthalates are used as plasticizers in polyvinyl chloride (PVC) plastics, as lubricants in certain rubbers (e.g. nitrile and neoprene), and as fixatives (or carriers) in perfumes and fragrances (Stanley et al., 2003; Wypych, 2004). Phthalates are not covalently bound to polymeric materials and can migrate to the environment over time resulting in human exposure. Sources of phthalate exposure include the work- place, diet, off-the-job activities, personal care products, and other home or environmental sources. Phthalates have been evaluated as possible reproductive and developmental toxicants in animals and humans (Hauser and Calafat, 2005; Latini, 2005; Heudorf et al., 2007; Matsumoto et al., 2008) and may also have a function in respiratory disease (Bornehag et al., 2004; Hoppin et al., 2004; Jaakkola and Knight, 2008; Kolarik et al., 2008). Sensitive and specific analytical methods have been developed over the past decade to measure concentrations of phthalate metabolites in urine (Koch et al., 2003a; Itoh et al., 2005; Kato et al., 2005; Preuss et al., 2005; Silva et al., 2007, 2004). Phthalate urinary metabolite concentrations can be used in simple pharmacokinetic models to estimate daily intake (David, 2000; Kohn et al., 2000). These models assume steady state excretion of metabolites and a constant daily creatinine excretion (CE) rate, conditions that depend on the temporal variability of the phthalate exposure and the characteristics of the sampled individual. When multiple individuals are monitored in a given exposure setting, some of this temporal variability may be accounted for by averaging intake estimates across the group. Intake estimates can be useful for risk assessment by comparing them to chronic oral reference doses (RfDs) established by the U.S. Environmental Protection Agency (EPA) (U.S. EPA, 2007a,b,c,d) and to tolerable daily intakes (TDIs) established by the European Food Safety Authority (EFSA). (EFSA (European Food Safety Authority), 2005a, b, c). The RfD (or TDI) is an estimate of the daily exposure to the human population (including sensitive subgroups) that is likely to be without appreciable risk of deleterious effects during a lifetime. Biomonitoring for phthalate exposure offers the advantages of integrating exposure across all routes (e.g. Received 26 June 2009; accepted 4 November 2009; published online 16 December 2009 1. Abbreviations: boot, rubber boot; cmpd, PVC compounding; film, PVC film; filt, vehicle filters; gask, rubber gasket; hose, rubber hose; manf, phthalate manufacturing; nail, nail-only salons 2. Address all correspondence to: Cynthia J. Hines, National Institute for Occupational Safety and Health, 4676 Columbia Pkwy, R-14, Cincinnati, 45230, USA. Tel.: 513 841 4453. Fax: 513 841 4486. E-mail: cjh8@cdc.gov Journal of Exposure Science and Environmental Epidemiology (2011) 21, 133–141 r 2011 Nature America, Inc. All rights reserved 1559-0631/11 www.nature.com/jes