Authors did not report the cross-sectional risk of atopy to common allergens from exposure to formaldehyde. They hypothesized that formaldehyde causes inflammation and the release of cytokines, which leads to the upregulation of inducible NO synthetase. This view was supported by another study that found intranasal exposure to 400 ppb formaldehyde in healthy subjects caused eosinophilia in the nasal epithelium . Given that a key marker of the asthmogenic effects of formaldehyde may be specific IgE to formaldehyde-albumin, other air toxics could be similarly screened to evaluate their potential influence on atopic responses.Some experimental evidence in controlled human exposure studies supports an respiratory irritant mechanism for VOCs , but the human experimental research on lower respiratory or pulmonary immunologic effects of VOCs is scarce apart from studies of agents associated with occupational asthma . Koren et al. conducted a randomized crossover chamber study of 14 healthy nonsmoking young adult men. Subjects were exposed for 4 hr 1 week apart to clean air and 25 µg/m3 of a VOC mixture typical of indoor nonindustrial micro-environments. Nasal lavage performed immediately after exposure and 18 hr later showed significant increases in neutrophils at both time points. Harving et al. conducted a randomized crossover chamber study of 11 asthmatic individuals who were hyperreactive to histamine. Subjects were exposed for 90 min, 1 week apart to clean air and VOC mixtures at 2.5 and 25 µg/m3. Investigators found FEV1 decreased to 91% of baseline with 25 µg/m3, but this was not significantly different from sham exposure,indoor plant growing rack and there was no change in histamine reactivity. It is possible that the null results do not reflect inflammatory changes that influence small airways, which could be missed with FEV1 measurements.
What may be occurring in natural environments is another story, with mixed exposures possibly interacting under a wide range of exposure–dose conditions. This is best investigated with epidemiologic designs.Indirect evidence of a role for ambient VOCs in asthma comes from research linking a buildup of indoor irritants including VOCs and bio-aerosols in office buildings to a nonspecific cluster of symptoms called the “sick building syndrome,” which includes upper and lower respiratory tract symptoms, eye irritation, headache, and fatigue. Other studies have also found new-onset asthma occurring in relation to particular nonresidential indoor environments, especially where problems with ventilation systems or dampness have been found . It is possible that fungal spores or other aeroallergens, mycotoxins, and endotoxins could increase in parallel with VOCs under conditions of inadequate air exchange at work, and be responsible for some of these findings. Epidemiologic evidence linking indoor home VOCs with asthma or related respiratory outcomes come largely from cross-sectional studies. A survey of 627 students 13–14 years of age attending 11 schools in Uppsala, Sweden, showed self-reported asthma prevalence was higher in schools with higher VOCs . Other risk factors were not controlled for in this association. In addition, passive, not active, VOC measurements were associated with asthma. Norbäck et al. , using a survey sample of 600 adults 20–44 years of age in Uppsala, Sweden, selected a nonrandom sub-sample of 47 subjects reporting asthma attacks or nocturnal breathlessness the last 12 months or reporting current use of asthma medications.Logistic regression models adjusted for age, sex, smoking, carpeting, and house dust mites, but not dampness, which was significant. There were no effects on daytime breathlessness from concentrations of 2-hr active VOC samples in the homes. Nocturnal breathlessness was associated with toluene, C8-aromatics, terpenes, and formaldehyde in adjusted models. Bronchial hyper responsiveness was correlated only with limonene.
PEF variability was correlated only with terpenes. Wieslander et al. aimed to examine respiratory symptoms and asthma outcomes in relation to indoor paint exposures in the last year. They selected an enriched random sample of 562 adult subjects, including asymptomatic responders along with all reporting asthma or nocturnal dyspnea , using the same survey source population as Norbäck et al. in Uppsala. Asthma was defined as positive bronchial hyper responsiveness to methacholine plus asthma symptoms . Thirty-two percent of homes and 23% of workplaces were painted within the last year. Total VOC was elevated by 100 µg/m3 in 62 newly painted homes. Logistic regression models adjusted for age, sex, and current smoking but not ETS. Asthma prevalence was greater for newly painted homes [OR 1.5 ], consistent with greater differences in VOCs . Blood eosinophil concentrations were also elevated in newly painted homes. In newly painted workplaces, asthmalike symptoms were significantly increased , but there was no association with bronchial hyper responsiveness or eosinophils. There were no associations for newly painted homes or workplaces and atopy , serum eosinophilic cationic protein, serum IgE, PEF variability , or in-clinic FEV1. Biases in the above cross-sectional studies in Uppsala include potential selection bias and the possibility that health outcomes preceded exposures. Diez et al. studied 266 newborn children born with birth weight of 1,500–2,500 g, or with elevated IgE in cord blood, or with a positive primary family history of atopic disease. Concentrations of 25 VOCs were monitored indoors during the first 4 weeks of life. Parents filled out questionnaires after 6 weeks and 1 year of age. Postnatal respiratory infections were associated with benzene > 5.6 µg/m3 [OR 2.4 ] and styrene > 2.0 µg/m3 [OR 2.1 ]. Wheezing was associated with reports of restoration during the first year of life, but not with total or specific IgE at the age of 1 year. These models controlled for heating, gas cooking, home size, new furniture, and animals but did not control for significant effects of ETS, which was correlated with benzene.
All of the above studies of indoor VOCs may be subject to unmeasured confounding by other causal agents that increase indoors under low ventilation conditions, including aeroallergens, or that are correlated with VOCs for other reasons. Most, but not all, of the studies controlled for ETS. The research to date is too sparse to evaluate causality from indoor home VOCs, but there is even less information to evaluate the public health impact on respiratory health from outdoor VOCs, which include some of the same compounds found indoors. Ware et al. conducted a study in a large chemical manufacturing center in the Kanawha Valley, West Virginia. They surveyed 74 elementary schools with interviews of 8,549 children in and out of the valley and measured passive 8-week samples of 5 petroleum-related VOCs and 10 process related VOCs . Higher VOC concentrations were found in the valley. Cross-sectional results showed children in the valley had higher rates of physician-diagnosed asthma [OR 1.27 ]. Composite indicators for lower respiratory symptoms in the last year were weakly positively associated with petroleum-related VOC levels [OR per 10 µg/m3, 1.05 ] and process-related VOCs levels [OR per 2 µg/m3, 1.08 ]. Asthma diagnoses were weakly positively associated with petroleum-related VOCs [OR 1.05 ] but not process related VOCs . One school with high petroleum-related VOCs strongly influenced the model. The average concentrations measured in the Kanawha study do not differ greatly from average levels in large urban areas . For the Kanawha study compared with a Los Angeles ambient exposure study, for example, average toluene was 9.7 µg/m3 versus 13 µg/m3, respectively, and for benzene, 3.2 µg/m3 versus 3.5 µg/m3, respectively . In a study of 51 residents of Los Angeles, personal and indoor air concentrations of all prevalent VOCs except carbon tetrachloride were higher than outdoor ambient concentrations . Also,marijuana growing racks personal real time exposures can be even higher, particularly while in cars . For example, measurements of toluene taken inside cars in New York City ranged from 26 to 56 µg/m3 and for benzene ranged from 9 to 11 µg/m3 . Active ingredients in insecticide products used in residential and agricultural environments have changed over time due in part to regulations implemented to protect human health and the environment. Organochlorine insecticides such as dichlorodiphenyltrichloroethane were introduced in the 1940’s and used to treat termites and other insects in homes. DDT was banned from all use in the United States in 1972 due to concerns about ecological and human health.1 Chlordane, another OC insecticide, replaced DDT until it, too, was banned for residential use in 1988 due to concerns about potential carcinogenicity and developmental health effects.Organophosphate insecticides, including chlorpyrifos and diazinon, largely replaced OC insecticides for residential use beginning in the 1970’s. As a result of the Food Quality Protection Act of 1996 and in advance of a required phase out in 2005 due to concerns about exposure to children, sales of chlorpyrifos and diazinon for indoor home use were voluntarily ended by the manufacturers in 2001 and 2004, respectively.Carbamate insecticides, including carbaryl and propoxur, were widely used for residential indoor applications in the 1980’s and 1990’s but many registered residential uses have been cancelled, including all indoor applications of carbaryl in 2008,5 due to concerns about neurodevelopmental effects of carbamates and carcinogenic effects of propoxur,Synthetic pyrethroids, such as permethrin and cypermethrin, were developed as a less toxic alternative to OP and OC insecticides,and have largely replaced OPs and carbamates insecticides for residential uses.Carpet dust has been used as an indicator of potential long-term exposure in the residential environment for non-volatile and semi-volatile compounds because the indoor environment is protected from light, weather and microbes that degrade compounds outdoors.
Carpet dust is an especially good environmental medium for assessing exposure to children because they spend more time on the floor and have more hand-to-mouth activity than adults,resulting in greater estimated intake of chemicals from non-dietary ingestion.Based on exposure models for children three to five years of age, estimated non-dietary ingestion was the primary route of exposure to permethrin in U.S. homes with self-reported use of the insecticide,and to chlorpyrifos and diazinon among farmworkers’ children from an agricultural community in California.Sources of insecticides inside the home include indoor and outdoor residential applications,occupational take-home,16 and drift from nearby agricultural applications.In this study, we collected carpet dust from children’s homes between 2001 and 2006 and measured the concentrations of eight insecticides. This study provided an opportunity to evaluate changes in concentrations of insecticides in carpet dust over time, while adjusting for important covariates, such as home insect treatments and nearby agricultural use. The results of our analyses provide information on the impact of regulatory changes on indoor levels of these insecticides. Our analysis included 413 residences from the Northern California Childhood Leukemia Study , a population-based case-control study in 17 counties in the San Francisco Bay area and 18 counties in the Central Valley.A single carpet dust sample was collected from a subset of NCCLS homes between October 2001 and April2006. Homes were eligible for carpet dust sample collection if the child was < 8 years old at diagnosis and lived in the same home since he/she was diagnosed with leukemia and had a carpet or area rug that was at least one square meter in area. Our analysis also included 21 residences from the Agricultural Pesticide Study in Fresno, California, which was designed to evaluate temporal variability in levels and determinants of exposure to agricultural pesticides.Eligibility criteria for APS residences included having at least 25% of land within 500 m of the home in agricultural production and no residents working in pesticide-related jobs during the previous six months. All APS homes had at least 2.2 m2 of carpet or rugs that had been in the residence for at least one year and each home was visited from one to seven times between April 2003 and November 2005. Both study protocols were approved by the Institutional Review Boards of participating institutions and all participants gave written informed consent prior to participation. A dust sample was collected from each residence at the home visit, as described previously,using a High Volume Small Surface Sampler . For NCCLS participants, the dust sample was taken from a carpet or rug in the room where the child spent the most time while awake in the year prior to diagnosis/reference date to provide the best estimate of exposure since the bedroom would include time spent sleeping when the child would not be in contact with the carpet. For APS participants, a sample was collected from a carpet or rug in the room located on the side of the home facing agricultural fields at each home visit. Interview staff collected approximately 10 mL of dust.