Occupational exposure to VOCs and formaldehyde are associated with some of the samesymptoms as SBS . However, levels of these compounds in office and other buildings are considerably lower than those found in industrial settings. Concentrations of total VOC in office buildings commonly range between less than 100 µg/m3 and several thousand micrograms per cubic meter, but maximum values of up to 50,000 µg/m3 have been reported . More than 350 VOCs have been detected at concentrations exceeding 1 ppb in indoor air , but generally only about 30 to 70 are routinely measured and even fewer are consistently detected in a majority of office buildings . When a group of Nordic scientists reviewed the literature up to early 1996 regarding VOC/ TVOC and health, they concluded that neither exposure nor epidemiological studies provided conclusive evidence that TVOC provided a risk index for health and comfort effects in buildings . A similar conclusion was reached in a review of studies that examined the association between SBS symptoms and indoor airborne PM, to which VOC can be adsorbed . However, the Nordic scientists stated that indoor air pollution, including VOCs, was most likely causally linked to effects on health and comfort. They also emphasized that there were “problems of principle with the concept of TVOC as such” because it is poorly defined— that is, it refers to different mixtures of chemicals with varying biological effects and is used in an unsystematic manner. Additionally, the use of various different sampling and analytical methods constitutes a major source of variability between studies . There are various other problems with the way current assessments of factors related to SBS symptoms are conducted. Measurements are often taken in only a few locations in a building, without accounting for the fact that there are microclimates in buildings resulting from differences in the ventilation rates,cannabis grow supplier in the number of occupants and the amount of bio-effluents they produce, and in the furnishing and equipment and, therefore, in the sources of chemical compounds and their source strength.

Additionally, symptoms are generally assessed via questionnaires, and these differ between studies and are not always validated. The period for which symptoms are assessed also varies from the single day on which environmental measurements are taken to as long as the previous year. In several studies, there is a considerable lapse of time between these measurements and the assessment of symptoms. The number and type of factors included as covariates or confounders in the statistical analysis also varies substantially between studies. Additionally, none of the available studies that we reviewed accounted for the fact that people are exposed to a wide variety of chemicals in micro-environments other than the workplace—particularly at home, where they spend the majority of their time. These considerations may explain the frequent failure to detect an association between VOC/TVOC and SBS. Various other hypotheses have been proposed to explain why VOCs may be an important factor in SBS, although the evidence is inconclusive . For example, it is possible that SBS is associated with a subgroup or subgroups of VOCs rather than TVOC and/or with intermediates or products of reactions between certain types of VOCs and ozone or various reactive oxygen and nitrogen species. Principal component analysis has become an important tool for identifying groups of chemicals and other factors that could explain the different frequencies of SBS symptoms in different buildings. It condenses a set of highly correlated variables into a smaller number of linearized sums . This works particularly well for VOCs because subsets of them have common sources. Because VOCs can originate from more than one source, they can be associated with more than one PC. PCA on a total of 39 VOCs measured in 12 California office buildings was used to identify exposure metrics—that is, mathematical expressions of the potential or actual agent that causes an adverse health effect . The exposure metric termed irritancy/PC emerged as the most significant predictor of irritant symptoms.

It consisted of the two most relevant vectors obtained by PCA, which were identified as representing carpet and building material emissions and emissions from cleaning products and water-based paint; it also accounted for the irritancy of VOCs relative to toluene. When analyzed separately, the cleaning products and water-based paints source vector provided the most important symptom prediction, with statistically significant adjusted ORs ranging from 1.7 to 2.2 for eye, skin, throat, stuffy nose, and overall symptoms. Other studies that used PCA on VOCs, but without accounting for their irritancy, linked photocopier emissions to mucous membrane symptoms; paint-derived VOCs to sore throat symptoms; construction material emission to dry eyes, mucous membrane symptoms overall, and short breath; and VOCs associated with furniture coating to shortness of breath . A combination of PCA and partial least squares analysis of VOCs desorbed from dust samples from nine office buildings identified a set of compounds that could account for 80% of the variance in the frequency of mucous membrane complaints and another set of compounds that explained 66% of the variance in difficulty concentrating . The possibility that oxidative degradation products of α- or β- pinene were among the compounds associated with mucous membrane irritation was particularly intriguing. As discussed later, the oxidation of terpenes produces formaldehyde and other aldehydes, and there are indications that some considerably more irritating substances are also formed. PCA was also used to identify factors that would be able to distinguish buildings with a high prevalence of SBS symptoms from those with a low prevalence of SBS symptoms . The most complex model was able to separate 71% of high-prevalence from low-prevalence buildings, and the most important variable was the higher concentration or more frequent detection of compounds with higher retention times in gas chromatography analysis in buildings with a low prevalence of symptoms.In five office buildings with different frequencies of reported SBS symptoms, cluster analysis was used to identify “hot” and “cold” spots—that is, areas with high and low symptom frequencies—in each building . Only people working in areas where chemical and other measurements had been taken were included in the analysis.

The most striking finding was that the same factors were associated with different symptoms and the same symptoms were associated with different factors in the various buildings. Furthermore, a recent comparison of personal exposures to aldehydes, amines, NO2 , O3 , particles, and VOCs in eight office buildings in a town in northern Sweden found that intra-individual differences accounted for the variation of 78% of the 123 measured compounds, whereas differences among buildings were the major source of variability for only 14% of the compounds . This highlights the inadequacy of a few stationary measurements in buildings and underscores the need for personal exposure measurements. Weschler and Shields noted that the inability to identify irritants in an indoor setting does not mean that the setting is free of irritants but may simply reflect the difficulty or even impossibility to detect the relevant compound with the analytical techniques routinely used to monitor indoor air quality. It may not be the VOCs that cause SBS symptoms; rather, it may be reaction products,cannabis drainage system particularly the reaction of unsaturated VOCs with O3 and various oxygen and nitrogen radicals . The major source of O3 in indoor air is outdoor-to-indoor transport . Additionally, office equipment, such as laser printers and photocopiers, has been shown to emit not only VOC but also O3 . Monoterpenes are unsaturated VOCs that contain one or two double bonds that react readily with O3 , OH radicals, and nitrate radicals to yield various aldehydes, ketones, carboxylic acids, and organic nitrates . The reaction of terpenes at concentrations below their no observed effect level with O3 yielded reaction products that acted as strong airway irritants in an established mouse bio-assay . Although known irritants were among the reaction products, they did not fully account for the observed effect, suggesting that one or more highly irritating intermediates and/or as yet unidentified products were formed. A possible candidate is submicron particles, which have been shown to form when O3 reacts with terpenes under simulated office conditions . Modeling and experimental measurements demonstrated that the product formation of uni- and bimolecular reactions increased at decreasing ventilation rates, whether or not there was sufficient time for the system to achieve steady state .Therefore, the decrease in SBS symptom frequency observed with increasing ventilation rates is likely to reflect not only the removal of pollutants with indoor sources but the restriction of reactions among indoor pollutants. A study of 29 office buildings in northern Sweden is frequently cited to support the hypothesis that reaction products, rather than VOCs themselves, are associated with SBS symptoms . Compared with buildings where TVOCs were higher in the room air than in the intake air, buildings where VOCs were “lost” from intake to room air had an OR of 39 of being SBS buildings .

The more TVOCs were lost, the higher the concentration of formaldehyde was, providing indirect confirmation of prior experimental data and indicating that VOCs reacted with O3 to form various aldehydes, including formaldehyde . A major shortcoming of this study is that VOCs were measured up to 6 mo after SBS symptoms had been assessed by questionnaire. Furthermore, PCA of the data from the same 29 office buildings did not confirm the significant association of lost TVOCs with the prevalence of SBS symptoms . However, this may have been attributable to the simultaneous “loss” and “gain” of TVOCs in separate rooms within the same building. It is rather striking that investigations of the possible associations between VOCs and SBS have focused exclusively on VOCs at the workplace, although exposure occurs in almost all micro-environments—particularly at home, but also in cars, public transportation, restaurants, pubs, stores, and movie theaters . Although rather different half-lives of elimination have been reported for VOCs from blood, there is general agreement that VOCs are rapidly taken up and that their elimination is characterized by a two-exponential, and in some cases a three-exponential, equation . This suggests that blood VOCs are distributed to multiple tissues for storage and that the kinetics of elimination vary with the storage site. This is confirmed by measurements of VOCs in breath, which suggest that under steady state conditions, the residence times for bloodor liver, organs, muscle, and fat are approx 3 min, 30 min, 3 h, and 3 d, respectively . From these data, it appears possible that bio-accumulation occurs and, therefore, that not only the kinetics of VOC uptake and elimination but also the threshold for adverse health effects may differ after acute and chronic exposure. It remains to be established whether cumulative exposure to certain groups of VOCs is a better predictor of SBS symptoms than exposure in the work environment alone.In recent years, several environmental monitoring studies other than those attempting to identify factors involved in SBS symptoms have focused on VOC exposure. A major impetus for such studies was provided by the fact that several VOCs are among the 189 hazardous air pollutants listed in the US Clean Air Act Amendment. These include the known human carcinogens, benzene and 1,3-butadiene, and the probable human carcinogens, styrene, methylene chloride, and carbon tetrachloride. The International Agency for Research on Cancer also recently reclassified formaldehyde from Group 2A to Group 1 . Until recently, the majority of research on VOCs focused on identifying exposures in outdoor air, but data on indoor residential exposure to VOCs are beginning to accumulate . In studies measuring personal and residential indoor as well as outdoor concentrations of VOCs, personal exposure of adults and children generally exceeded residential indoor exposure by a substantial margin, and indoor concentrations were considerably higher than outdoor levels . An analysis of data on personal, residential indoor and outdoor, and work environment indoor concentrations of VOCs in Helsinki, Finland indicated that the geometric means of residential concentrations of VOCs exceeded those of work environments . Notably, the sample was representative of the population of Helsinki and included people with occupational exposures to VOCs, as indicated by the high maxima reported for the work environment, which were two orders of magnitude higher than mean residential concentrations.