The potential of sheep in preclinical models for bone infection research - A systematic review.

Background: Reliable animal models are critical for preclinical research and should closely mimic the disease. With respect to route of infection, pathogenic agent, disease progression, clinical signs, and histopathological changes. Sheep have similar bone micro- and macrostructure as well as comparable biomechanical characteristics to humans. Their use in bone research is established, however their use in bone infection research is limited. This systematic review will summarise the key features of the available bone infection models using sheep, providing a reference for further development, validation, and application. Method: This systematic review was designed according to the PRISMA guidelines and registered with PROSPERO. Quality was assessed using SYRICLE's risk of bias tool adapted for animal studies. PubMed, MEDLINE, Web of Science and EMBASE were searched until March 2022.1921 articles were screened by two independent reviewers, and 25 were included for analysis. Results: Models have been developed in nine different breeds. Staphylococcus aureus was used in the majority of models, typically inoculating 108 colony forming units in tibial or femoral cortical defects. Infection was established with either planktonic or biofilm adherent bacteria, with or without foreign material implanted. Most studies used both radiological and microbiological analyses to confirm osteomyelitis. Conclusions: There is convincing evidence supporting the use of sheep in bone infection models of clinical disease. The majority of sheep studied demonstrated convincing osteomyelitis and tolerated the infection with minimal complications. Furthermore, the advantages of comparable biology and biomechanics may increase the success for translating in vivo results to successful therapies. The Translational potential of this article: In the realm of preclinical research, the translation to viable clinical therapies is often perilous, and the quest for reliable and representative animal models remains paramount. This systematic review accentuates the largely untapped potential of sheep as large animal models, especially in bone infection research. The anatomical and biomechanical parallels between sheep and human bone structures position sheep as an invaluable asset for studying osteomyelitis and periprosthetic joint infection. This comprehensive exploration of the literature demonstrates the robustness and translational promise of these models. Furthermore, this article underscores the potential applicability for sheep in developing effective therapeutic strategies for human bone infections.

Efficacy, toxicity, and quality-of-life outcomes of ultrahypofractionated radiotherapy in patients with localized prostate cancer: A single-arm phase 2 trial from Asia.

AIMS: Ultra-hypofractionated radiotherapy (UHF-RT) is widely utilized in men with localized prostate cancer (PCa). There are limited data in Asian cohorts. We report the outcomes of a single-arm, phase II trial of UHF-RT from an Asian center. METHODS: We recruited men with histologically confirmed, nonmetastatic localized PCa. UHF-RT regimens were 36.25 Gy (Cohort A) and 37.5 Gy (Cohort B) delivered in five fractions every other day over 1.5-2.5 weeks. Primary endpoint was physician-scored late genitourinary (GU) and gastrointestinal (GI) adverse events (AEs). Quality-of-life (QoL) was assessed by Expanded Prostate Cancer Index Composite (EPIC) at baseline, 1- and 2-year post-UHF-RT. RESULTS: Between March 2014 and August 2019, 105 men were recruited; four were subsequently excluded from analysis. Median age was 68.0 (Interquartile range (IQR): 63.8-73.0) years. 26 (24.8%) and 68 (64.8%) men had NCCN-defined low-and intermediate-risk PCa, respectively. No late ≥G3 GU or GI toxicities were reported in both cohorts. Peak incidence of acute ≥G2 GU AEs at 14 days post-UHF-RT was 23.6% (17/72) and 24.0% (6/25) in Cohorts A and B, respectively; ≥G2 GI AEs were observed in 9.7% (7/72) and 36.0% (9/25), respectively. Late ≥G2 GU and GI AEs occurred in 4.7% and 3.1% of Cohort A patients, and 5.0% in Cohort B at 12 months, with no AEs at 24 months. EPIC scores changed minimally across all domains. At a median follow-up of 44.9 months, we recorded one (1.3%) biochemical relapse by the Phoenix criteria (Cohort A). CONCLUSION: UHF-RT is well tolerated in Asian men and can be a recommended fractionation schema for localized PCa.

Real-World Data on Clinical Outcomes of Patients with Liver Cancer: A Prospective Validation of the National Cancer Centre Singapore Consensus Guidelines for the Management of Hepatocellular Carcinoma.

INTRODUCTION: Real-world management of patients with hepatocellular carcinoma (HCC) is crucially challenging in the current rapidly evolving clinical environment which includes the need for respecting patient preferences and autonomy. In this context, regional/national treatment guidelines nuanced to local demographics have increasing importance in guiding disease management. We report here real-world data on clinical outcomes in HCC from a validation of the Consensus Guidelines for HCC at the National Cancer Centre Singapore (NCCS). METHOD: We evaluated the NCCS guidelines using prospectively collected real-world data, comparing the efficacy of treatment received using overall survival (OS) and progression-free survival (PFS). Treatment outcomes were also independently evaluated against 2 external sets of guidelines, the Barcelona Clinic Liver Cancer (BCLC) and Hong Kong Liver Cancer (HKLC). RESULTS: Overall treatment compliance to the NCCS guidelines was 79.2%. Superior median OS was observed in patients receiving treatment compliant with NCCS guidelines for early (nonestimable vs. 23.5 months p < 0.0001), locally advanced (28.1 vs. 22.2 months p = 0.0216) and locally advanced with macrovascular invasion (10.3 vs. 3.3 months p = 0.0013) but not for metastatic HCC (8.1 vs. 6.8 months p = 0.6300), but PFS was similar. Better clinical outcomes were seen in BCLC C patients who received treatment compliant with NCCS guidelines than in patients with treatment only allowed by BCLC guidelines (median OS 14.2 vs. 7.4 months p = 0.0002; median PFS 6.1 vs. 4.0 months p = 0.0286). Clinical outcomes were, however, similar for patients across all HKLC stages receiving NCCS-recommended treatment regardless of whether their treatment was allowed by HKLC. CONCLUSION: The high overall compliance rate and satisfactory clinical outcomes of patients managed according to the NCCS guidelines confirm its validity. This validation using real-world data considers patient and treating clinician preferences, thus providing a realistic analysis of the usefulness of the NCCS guidelines when applied in the clinics.

The implementation of an advanced practice radiation therapy (APRT) program in Singapore.

BACKGROUND: The exploration of Advanced Practiced Radiation Therapists (APRTs) development in Singapore started in 2011. This study aims to provide an overview of the development of the APRT roles, and to discuss the approaches used to develop and implement these roles in Singapore. MATERIALS AND METHODS: A mixed methods approach was used in the development of the APRT program. A literature review was carried out to define the APRT scope of practice and core responsibilities. A competency and assessment framework were setup to assess the core competency areas. With this framework, a structured 1-year residency training program was developed. RESULTS: The scope of practice and core responsibilities of APRTs were defined with five proposed advanced practice profiles being successfully validated. A competency framework was set up to assess the core competency domains: clinical, technical and professional competencies, research, education and leadership. A 4-point scoring system was developed for the competency assessment based on two criteria; the frequency with which RTTs would demonstrate competency, and the ability of performing the task competently. A 1-year structured APRT residency program was developed and implemented. The programme consisted of structured lectures, and clinical practice-based modules where APRT residents receive structured mentoring under a mentorship program. CONCLUSION: The APRT program in Singapore employed an evidence-based implementation process that tested the feasibility of a new practice model. Multidisciplinary involvements, mentorship and clinical training were important factors for the success of the APRT program.

Early Outcomes of a National Cancer Center's Strategy Against COVID-19 Executed Through a Disease Outbreak Response Taskforce.

PURPOSE: We present the strategy of a comprehensive cancer center organized to make operations pandemic proof and achieve continuity of cancer care during the COVID-19 pandemic. METHODS: Disease Outbreak Response (DORS) measures implemented at our center and its satellite clinics included strict infection prevention, manpower preservation, prudent resource allocation, and adaptation of standard-of-care treatments. Critical day-to-day clinical operations, number of persons screened before entry, staff temperature monitoring, and personal protection equipment stockpile were reviewed as a dashboard at daily DORS taskforce huddles. Polymerase chain reaction swab tests performed for patients and staff who met defined criteria for testing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were tracked. Descriptive statistics of outpatient attendances and treatment caseloads from February 3 to May 23, 2020, were compared with the corresponding period in 2019. RESULTS: We performed COVID-19 swabs for 80 patients and 93 staff, detecting three cancer patients with community-acquired COVID-19 infections with no nosocomial transmission. Patients who required chemotherapy, radiotherapy, or surgery and patients who are on maintenance treatment continued to receive timely treatment without disruption. The number of intravenous chemotherapy treatments was maintained at 97.8% compared with 2019, whereas that of weekly radiotherapy treatments remained stable since December 2019. All cancer-related surgeries proceeded without delay, with a 0.3% increase in workload. Surveillance follow-ups were conducted via teleconsultation, accounting for a 30.7% decrease in total face-to-face clinic consultations. CONCLUSION: Through the coordinated efforts of a DORS taskforce, it is possible to avoid nosocomial SARS-CoV-2 transmissions among patients and staff without compromising on care delivery at a national cancer center.

Navigating the challenges of the COVID-19 outbreak: Perspectives from the radiation oncology service in Singapore.

In December 2019, pneumonia of unknown cause was reported by China to WHO. The outbreak was found to be caused by a coronavirus which was officially named "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2), and the disease caused by it was named 'COVID-19'. The first case in Singapore was confirmed on 23rd January 2020. With lessons learnt from the SARS epidemic in 2003 and the H1N1 flu pandemic in 2009, Singapore was much better prepared to deal with the virus outbreak. The government has taken swift measures to contain and break the chain of transmission. Healthcare workers face the challenge of keeping patients and staff safe from the disease. There is a higher risk of mortality of COVID-19 in cancer patients and hence unique considerations for a radiation oncology department operating in an infectious disease outbreak. This article is the recommendations and adapted workflow from the two National Cancer Centres in Singapore with the endorsement by the working committee of the Chapter of Radiation Oncology, Academy of Medicine, Singapore. It highlights the challenges that radiation oncology departments in Singapore face and the appropriate recommended responses. This includes interventions, business continuity plans and workflow in managing a COVID-19 positive patient on radiotherapy.

HDAC5 Expression in Urothelial Carcinoma Cell Lines Inhibits Long-Term Proliferation but Can Promote Epithelial-to-Mesenchymal Transition.

Class I histone deacetylases (HDACs) generally promote cell proliferation and tumorigenesis, whereas class IIA HDACs like HDAC4 and HDAC5 may promote or impede cancer development in a tissue-dependent manner. In urothelial carcinoma (UC), HDAC5 is often downregulated. Accordingly, HDAC5 was weakly expressed in UC cell lines suggesting a possible tumor-suppressive function. We therefore characterized the effects of stable HDAC5 expression in four UC cell lines (RT112, VM-Cub-1, SW1710 and UM-UC-3) with different phenotypes reflecting the heterogeneity of UC, by assessing proliferation, clonogenicity and migration ability. Further, we detailed changes in the proteome and transcriptome by immunoblotting, mass spectrometry and RNA sequencing analysis. We observed that HDAC5 overexpression in general decreased cell proliferation, but in one cell line (VM-Cub-1) induced a dramatic change from an epitheloid to a mesenchymal phenotype, i.e., epithelial-mesenchymal transition (EMT). These phenotypical changes were confirmed by comprehensive proteomics and transcriptomics analyses. In contrast to HDAC5, overexpression of HDAC4 exerted only weak effects on cell proliferation and phenotypes. We conclude that overexpression of HDAC5 may generally decrease proliferation in UC, but, intriguingly, may induce EMT on its own in certain circumstances.

68Gallium-labelled PSMA-PET/CT as a diagnostic and clinical decision-making tool in Asian prostate cancer patients following prostatectomy.

OBJECTIVE: Prostate cancers (PCa) in Asian individuals are molecularly distinct from those found in their Caucasian counterparts. There is no risk stratification tool for Asian men with rapid biochemical recurrence (BCR) following radical prostatectomy (RadP). This study aims to assess the detection rate of 68Ga-prostate-specific membrane antigen-positron emission tomography/computed tomography (PSMA-PET/CT) for diagnosis of clinical recurrence and as a treatment decision making tool in Asian patients with BCR post-RadP. METHODS: 68Ga PSMA-PET and CT body with/without bone scan [conventional workup (CWU)] were performed in 55 Asian patients with BCR within 36 months post-RadP. Two blinded reviewers assessed the images. Detection rates of 68Ga PSMA-PET/CT were evaluated, and impact on management was reviewed by comparison with CWU. RESULTS: Median time to BCR post-RadP was 8.1 months. Detection rate for 68Ga PSMA-PET/CT was 80% (44/55). A positive scan was significantly associated with increasing prostate-specific antigen (PSA) level [odds ratio (OR) = 1.13 (95% CI 1.05-1.30), P = 0.017], but not with higher Gleason grade or shorter PSA doubling time. Compared to CWU, 68Ga PSMA-PET/CT detected an additional 106 lesions in 33/44 patients with a positive scan, resulting in a change in management in 25/44 (56.8%) patients: 10 to hormonal therapy (HT) and whole pelvis radiotherapy (RT) in addition to bed RT, and 15 to palliative HT alone. CONCLUSIONS: In the present report, we demonstrated the diagnostic and treatment decision utility of 68Ga PSMA-PET/CT in Asian men with rapid BCR. Detection of small volume nodal and systemic recurrences at low PSA levels (< 1.0 ng/mL) highlights the role of the tool in assigning patients to treatment intensification with HT-RT or palliative HT in polymetastatic disease.

National Cancer Centre Singapore Consensus Guidelines for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the 6th most common cancer in the world, but the second most common cause of cancer death. There is no universally accepted consensus practice guidelines for HCC owing to rapid developments in new treatment modalities, the heterogeneous epidemiology and clinical presentation of HCC worldwide. However, a number of regional and national guidelines currently exist which reflect practice relevant to the epidemiology and collective experience of the consensus group. In 2014, clinicians at the multidisciplinary Comprehensive Liver Cancer Clinic (CLCC) at the National Cancer Centre Singapore (NCCS) reviewed the latest published scientific data and existing international and regional practice guidelines, such as those of the National Comprehensive Cancer Network, American Association for the Study of Liver Diseases and the Asian Pacific Association for the Study of the Liver, and modified them to reflect local practice. These would serve as a template by which treatment outcomes can be collated and benchmarked against international data. The NCCS Consensus Guidelines for HCC have been successfully implemented in the CLCC since their publication online on 26(th) September 2014, and the guidelines allow outcomes of treatment to be compared to international data. These guidelines will be reviewed periodically to incorporate new data.

Pesticide exposures to migrant farmworkers in Eastern NC: detection of metabolites in farmworker urine associated with housing violations and camp characteristics.

BACKGROUND: The purpose of this paper is to present and evaluate descriptively bivariate associations between urinary metabolites of pesticides and herbicides and migrant camp conditions, violations, and personal worker behaviors at home for farmworkers who do not apply pesticides. METHODS: We studied 183 migrant farmworker camps in eastern North Carolina in 2010. Data and urine samples were collected from 371 men. Predictor measures included violations in six domains of housing regulations and nonviolation characteristics and personal behaviors that might impact urinary metabolites. RESULTS: Cockroaches and bathroom violations were predictive of increased exposure to pyrethroids and cyfluthrin/chlorpyrifos, respectively. Changing and storing clothing and shoes in sleeping rooms increased the number of detects for the diazinon metabolite. CONCLUSIONS: Farmworkers had exposures to multiple chemicals. No single housing domain was identified as critical to mitigating housing-related exposure; specific attention should be paid to changing and storing soiled clothing in sleeping rooms, and insect infestations.

Properties of proxy-derived modified Rankin Scale assessment.

BACKGROUND: Cognitive or communication issues may preclude direct modified Rankin Scale interview, necessitating interview with a suitable surrogate. The clinimetric properties of this proxy modified Rankin Scale assessment have not been described. AIMS: To describe reliability of proxy-derived modified Rankin Scale and compare with traditional direct patient interview. METHODS: Researchers assessed consenting stroke inpatients and their proxies using a nonstructured modified Rankin Scale approach. Paired interviewers (trained in modified Rankin Scale) performed independent and blinded modified Rankin Scale assessment of patients and appropriate proxies. Interobserver variability and agreement between patient and proxy modified Rankin Scale were described using kappa statistics (k, 95% confidence interval) and percentage agreement. RESULTS: Ninety-seven stroke survivors were assessed. Proxies were family members (n = 29), nurses (n = 50), or physiotherapists (n = 25). Median modified Rankin Scale from both patient and proxies was 3 [interquartile range (IQR): 2-4]. Reliability for patient modified Rankin Scale interview was weighted kappa = 0·70 (95% confidence interval: 0·30-1·00). Reliability for proxy modified Rankin Scale weighted kappa = 0·62 (95% confidence interval: 0·34-0·90). Subgroup analysis of various proxy information sources were as follows: family weighted kappa = 0·61; nurse weighted kappa = 0·58; therapist weighted kappa = 0·58. There was disagreement between patient-derived modified Rankin Scale and corresponding proxy modified Rankin Scale weighted kappa = 0·64 (95% CI: 0·42-0·86). CONCLUSIONS: There is potential for substantial interobserver variability in proxy modified Rankin Scale and validity of certain proxy assessments is questionable. Direct modified Rankin Scale interview is preferred.

High-dose helical tomotherapy with concurrent full-dose chemotherapy for locally advanced pancreatic cancer.

PURPOSE: To improve poor therapeutic outcome of current practice of chemoradiotherapy (CRT), high-dose helical tomotherapy (HT) with concurrent full-dose chemotherapy has been performed on patients with locally advanced pancreatic cancer (LAPC), and the results were analyzed. METHODS AND MATERIALS: We retrospectively reviewed 39 patients with LAPC treated with radiotherapy using HT (median, 58.4 Gy; range, 50.8-59.9 Gy) and concomitant chemotherapy between 2006 and 2009. Radiotherapy was directed to the primary tumor with a 0.5-cm margin without prophylactic nodal coverage. Twenty-nine patients (79%) received full-dose (1000 mg/m(2)) gemcitabine-based chemotherapy during HT. After completion of CRT, maintenance chemotherapy was administered to 37 patients (95%). RESULTS: The median follow-up was 15.5 months (range, 3.4-43.9) for the entire cohort, and 22.5 months (range, 12.0-43.9) for the surviving patients. The 1- and 2-year local progression-free survival rates were 82.1% and 77.3%, respectively. Eight patients (21%) were converted to resectable status, including 1 with a pathological complete response. The median overall survival and progression-free survival were 21.2 and 14.0 months, respectively. Acute toxicities were acceptable with no gastrointestinal (GI) toxicity higher than Grade 3. Severe late GI toxicity (≥ Grade 3) occurred in 10 patients (26%); 1 treatment-related death from GI bleeding was observed. CONCLUSION: High-dose helical tomotherapy with concurrent full-dose chemotherapy resulted in improved local control and long-term survival in patients with LAPC. Future studies are needed to widen the therapeutic window by minimizing late GI toxicity.

Osteoradionecrosis of the cervical spine complicated by pneumocephalus and meningitis in a nasopharyngeal cancer patient radically treated with radiotherapy 11 years ago.

Superimposed infection of osteoradionecrotic cervical spine with cranial extension is difficult to treat and potentially fatal. This report describes the case of a middle-aged Chinese man 11 years post radical radiotherapy for nasopharyngeal cancer with no evidence of disease presenting initially with neck pain secondary to cervical osteoradionecrosis. He was re-admitted a month later with aspiration pneumonia associated with Streptococcus milleri bacteraemia, complicated by septic shock. The last re-admission was 2 months later with fever, expressive dysphasia and right upper motor neuron signs. There was interval increase of dental and peridental soft tissue mass, interval widening of atlantodental distance on MRI cervical spine associated with pneumocephalus, meningeal enhancement and pre-pontine soft tissue mass on CT brain consistent with infected osteoradionecrotic cervical spine complicated by cranial extension. The patient also had concomitant bilateral pneumonia and subsequently passed away from fulminant sepsis.

An assessment of the data quality for NHEXAS--Part I: Exposure to metals and volatile organic chemicals in Region 5.

A National Human Exposure Assessment Survey (NHEXAS) was performed in U.S. Environmental Protection Agency (U.S. EPA) Region V, providing population-based exposure distribution data for metals and volatile organic chemicals (VOCs) in personal, indoor, and outdoor air, drinking water, beverages, food, dust, soil, blood, and urine. One of the principal objectives of NHEXAS was the testing of protocols for acquiring multimedia exposure measurements and developing databases for use in exposure models and assessments. Analysis of the data quality is one element in assessing the performance of the collection and analysis protocols used in NHEXAS. In addition, investigators must have data quality information available to guide their analyses of the study data. At the beginning of the program quality assurance (QA) goals were established for precision, accuracy, and method quantification limits. The assessment of data quality was complicated. First, quality control (QC) data were not available for all analytes and media sampled, because some of the QC data, e.g., precision of duplicate sample analysis, could be derived only if the analyte was present in the media sampled in at least four pairs of sample duplicates. Furthermore, several laboratories were responsible for the analysis of the collected samples. Each laboratory provided QC data according to their protocols and standard operating procedures (SOPs). Detection limits were established for each analyte in each sample type. The calculation of the method detection limits (MDLs) was different for each analytical method. The analytical methods for metals had adequate sensitivity for arsenic, lead, and cadmium in most media but not for chromium. The QA goals for arsenic and lead were met for all media except arsenic in dust and lead in air. The analytical methods for VOCs in air, water, and blood were sufficiently sensitive and met the QA goals, with very few exceptions. Accuracy was assessed as recovery from field controls. The results were excellent (> or = 98%) for metals in drinking water and acceptable (> or = 75%) for all VOCs except o-xylene in air. The recovery of VOCs from drinking water was lower, with all analytes except toluene (98%) in the 60-85% recovery range. The recovery of VOCs from drinking water also decreased when comparing holding times of < 8 and > 8 days. Assessment of the precision of sample collection and analysis was based on the percent relative standard deviation (% RSD) between the results for duplicate samples. In general, the number of duplicate samples (i.e., sample pairs) with measurable data were too few to assess the precision for cadmium and chromium in the various media. For arsenic and lead, the precision was excellent for indoor, and outdoor air (< 10% RSD) and, although not meeting QA goals, it was acceptable for arsenic in urine and lead in blood, but showed much higher variability in dust. There were no data available for metals in water and food to assess the precision of collection and analysis.

Identification of 1,3-butadiene, benzene, and other volatile organics from wok oil emissions.

As part of a program to determine the underlying factors responsible for genotoxicity and perhaps lung cancer risk in Chinese women, we qualitatively identified the volatile components emitted during the heating of cooking oils to 265 degrees C. 1,3-Butadiene, benzene, and a series of aldehydes, olefins, and saturated hydrocarbons were elucidated in vapors from Chinese rapeseed oil. On a relative basis, the intensity of 1,3-butadiene vapors from this were 15.7-, 6.3-, and 1.4-fold greater than in the vapors from peanut, soybean, and Canola oils, respectively. Thus, the Chinese rapeseed oil yielded a higher emission rate of 1,3-butadiene than the other three oils investigated. The benzene formation rate followed a similar trend, i.e., its intensity in Chinese rapeseed oil was 14-, 6.6-, and 1.7-fold greater than in vapors from peanut, soybean, and Canola oils, respectively.

Gasoline-contaminated ground water as a source of residential benzene exposure: a case study.

In a private residence using gasoline-contaminated ground water (approximately 300 micrograms/l benzene), a series of experiments were performed to assess the potential benzene exposures that may occur in the shower stall, bathroom, master bedroom, and living room as a result of a single 20-min, shower. Integrated fixed site SUMMA TM-polished canister and Tenax GC air samples were collected in the target microenvironments over 20, 60, and 240 min. periods. These results were compared with the long-term personal Tenax GC samples (6 h) and grab samples collected with glass, gas-tight syringes at 0, 10, 18, 20, 25, 25.5, and 30 min. Maximum benzene concentrations occurred in the shower stall (758-1670 micrograms/m3) and bathroom (366-498 micrograms/m3) during and immediately after the shower. Inhalation exposures in the shower stall during the 20-min. shower were 2.1-4.9 times higher than corresponding 20-min, bathroom exposures. The total benzene dose resulting from the shower was estimated to be approximately 281 micrograms, with 40% via inhalation and 60% via the dermal pathway. This total is 2 to 3.5 times higher than the mean inhalation dose received during a concurrent 6 h occupation of the house. These results indicate that domestic use of gasoline-contaminated water can produce relatively high benzene exposures that vary significantly according to an individual's proximity to the water use zone. The information in this document has been funded wholly or in part by the U.S. Environmental Protection Agency. It has been subjected to Agency review and approved for publication. Mention of trade names or commercial products does not constitute endorsement or recommendation for use. The entire experiment was reviewed and approved by the Research Triangle Institute Human Subjects Review Committee.

The influence of personal activities on exposure to volatile organic compounds.

Seven persons volunteered to perform 25 common activities thought to increase personal exposure to volatile organic chemicals (VOCs) during a 3-day monitoring period. Personal, indoor, and outdoor air samples were collected on Tenax cartridges three times per day (evening, overnight, and daytime) and analyzed by GC-MS for 17 target VOCs. Samples of exhaled breath were also collected before and after each monitoring period. About 20 activities resulted in increasing exposure to one or more of the target VOCs, often by factors of 10, sometimes by factors of 100, compared to exposures during the sleep period. These concentrations were far above the highest observed outdoor concentrations during the length of the study. Breath levels were often significantly correlated with previous personal exposures. Major exposures were associated with use of deodorizers (p-dichlorobenzene); washing clothes and dishes (chloroform); visiting a dry cleaners (1,1,1-trichloroethane, tetrachloroethylene); smoking (benzene, styrene); cleaning a car engine (xylenes, ethylbenzene, tetrachloroethylene); painting and using paint remover (n-decane, n-undecane); and working in a scientific laboratory (many VOCs). Continuously elevated indoor air levels of p-dichlorobenzene, trichloroethylene, 1,1,1-trichloroethane, carbon tetrachloride, decane, and undecane were noted in several homes and attributed to unknown indoor sources. Measurements of exhaled breath suggested biological residence times in tissue of 12-18 hr and 20-30 hr for 1,1,1-trichloroethane and p-dichlorobenzene, respectively.