Research Health Effects of a Mixture of Indoor Air Volatile Organics, Their Ozone Oxidation Products, and Stress Nancy Fiedler,1,2 Robert Laumbach,1,2 Kathie Kelly-McNeil,1,2 Paul Lioy,1,2 Zhi-Hua Fan,1,2 Junfeng Zhang,1,2,3 John Ottenweller,4 Pamela Ohman-Strickland,3 and Howard Kipen 1,2 1Department of Environmental and Occupational Medicine, University of Medicine and Dentistry of New Jersey–Robert Wood Johnson Medical School, Piscataway, New Jersey, USA; 2Environmental and Occupational Health Sciences Institute, Piscataway, New Jersey, USA; 3University of Medicine and Dentistry of New Jersey–School of Public Health, Piscataway, New Jersey, USA; 4Veterans Affairs Medical Center, East Orange, New Jersey, USA In our present study we tested the health effects among women of controlled exposures to volatile organic compounds (VOCs), with and without ozone (O3), and psychological stress. Each subject was exposed to the following three conditions at 1-week intervals (within-subject factor): VOCs (26 mg/m3), VOCs + O3 (26 mg/m3 + 40 ppb), and ambient air with a 1-min spike of VOCs (2.5 mg/m3). As a between-subjects factor, half the subjects were randomly assigned to perform a stressor. Subjects were 130 healthy women (mean age, 27.2 years; mean education, 15.2 years). Health effects measured before, during, and after each 140-min exposure included symptoms, neurobehavioral performance, salivary cortisol, and lung function. Mixing VOCs with O3 was shown to produce irritating compounds including aldehydes, hydrogen peroxide, organic acids, secondary organic aerosols, and ultraﬁne particles (particulate matter with aerodynamic diameter < 0.1 µm). Exposure to VOCs with and without O3 did not result in significant subjective or objective health effects. Psychological stress signiﬁcantly increased salivary cortisol and symptoms of anxiety regardless of exposure condition. Neither lung function nor neurobehavioral perfor- mance was compromised by exposure to VOCs or VOCs + O3. Although numerous epidemiologic studies suggest that symptoms are signiﬁcantly increased among workers in buildings with poor ventilation and mixtures of VOCs, our acute exposure study was not consistent with these epi- demiologic findings. Stress appears to be a more significant factor than chemical exposures in affecting some of the health end points measured in our present study. Key words: building-related illness, lung function, neurobehavioral, ozone, stress, symptoms, volatile organic compounds. Environ Health Perspect 113:1542–1548 (2005). doi:10.1289/ehp.8132 available via http://dx.doi.org/ [Online 21 July 2005] (Norback et al. 1990; Ryan and Morrow 1992). Therefore, we chose to include only women in our study and to expose subjects to chemical mixtures with and without psycholog- ical stress. We hypothesized that subjects would report signiﬁcantly greater symptom severity and would show a greater cortisol response when exposed to VOCs or VOCs + O3 with psychological stress compared with these expo- sure conditions without stress or to the MCA condition with or without psychological stress (hypothesis 2: exposure × stress interaction). In summary, indoor environmental quality is affected by numerous factors, including bio- logical, chemical, and particulate pollutants; temperature and humidity; quality of the heat- ing, ventilation, and air conditioning system; noise; light; and odor (Mendell and Heath 2005). Our present study assessed the interac- tion of chemical pollutants and psychological stress on subjective (i.e., symptoms) and objective (i.e., cortisol, lung function, neu- robehavioral performance) indicators of health effects, while holding temperature, humidity, noise, and light constant. Furthermore, our study added an untested exposure dimension created by combining VOCs with O3, shown in previous studies to produce a suite of irri- tating gas and condensed-phase products (Fan et al. 2003). Materials and Methods Subjects One hundred thirty healthy, nonsmoking women, who were on average 27.2 years of age (SD = 8.0) with 15.2 (SD = 1.9) years of edu- cation, were recruited via advertisements in local newspapers. The ethnic composition of the sample was as follows: Caucasian, 56% Address correspondence to N. Fiedler, Environ- mental and Occupational Health Sciences Institute, UMDNJ-Robert Wood Johnson Medical School, 170 Frelinghuysen Rd., Room 210, Piscataway, NJ 08854 USA. Telephone: (732) 445-0123 Ext. 625. Fax: (732) 445-0130. E-mail: nﬁedler@eohsi.rutgers.edu Funding for our research was supported by a grant from the National Institute for Occupational Safety and Health (R01 OH03691-01) and by National Institute of Environmental Health Sciences Center grant ES05022. The authors declare they have no competing ﬁnancial interests. Received 21 March 2005; accepted 21 July 2005. VOLUME 113 | NUMBER 11 | November 2005 • Environmental Health Perspectives Between 800,000 and 1.2 million buildings in the United States may be associated with building-related illnesses, and thus, between 30 and 70 million workers are exposed to poten- tially unhealthy working conditions (Kreiss 1990; Woods 1989). Mixtures of volatile organic compounds (VOCs) and ozone (O3) are prominent pollutants in indoor environ- ments (Fan et al. 2003). In some cases, VOCs measured in office buildings are associated with complaints of mucosal irritation and non- speciﬁc symptoms such as headache (Hodgson et al. 1991; Ten Brinke et al. 1998). Further- more, healthy men and women intentionally exposed to similar mixtures of VOCs report increased symptoms of eye, nose, and throat irritation and reduced air quality ratings relative to clean air conditions (Hudnell et al. 1992; Prah et al. 1998). The number of symptoms reported in controlled exposure studies, how- ever, are relatively few and of mild intensity compared with the ongoing complaints of ofﬁce workers (Apter et al. 1994; Mendell and Smith 1990; Nordstrom et al. 1994; Zweers et al. 1992). Thus, some investigators suggest that when O3 reacts with VOCs in building environments, secondary products including ultraﬁne particles (particulate matter with aero- dynamic diameter < 0.1 mµ) may mediate the 1542 more substantial effects found in ofﬁces (Bako- Biro et al. 2004; Fan et al. 2003; Rohr et al. 2002; Weschler and Shields 2000; Wolkoff and Nielsen 2001). Our study assesses a selected suite of subjective and objective mark- ers in response to the following exposure condi- tions: VOCs, VOCs + O3, and ambient air with a 1-min spike of VOCs [masked clean air (MCA)]. We hypothesized that exposure to VOCs or VOCs + O3 would result in greater symptom severity, compromised neurobehav- ioral performance, reduced lung function, and increased salivary cortisol relative to the MCA exposure (hypothesis 1: exposure main effect). Gender and psychological stress also con- tribute to health complaints in buildings (Crawford and Bolas 1996; Hodgson 1995; Mendell 1993). For example, Bachmann and Myers (1995) found gender and psychological symptoms to be signiﬁcant predictors of symp- toms in two problem and one nonproblem building. Temperature, uncomfortable humid- ity, and reported odors, however, were also associated with symptoms in the buildings investigated. Women consistently report the highest prevalence of symptoms (Skov et al. 1989; Stenberg and Wall 1995), although external psychological stress (work load and control) is also associated with complaints