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At least 1,153 records · Page 64Linked to original sources
PubMed2006

Effects of combined, multiple stressors on pyridostigmine-induced acute toxicity in rats.

A number of studies have evaluated the possibility that stress-induced changes in blood-brain barrier permeability enhanced the central effects of the carbamate acetylcholinesterase inhibitor, pyridostigmine. We previously found relatively little evidence of stress-induced changes in the acute toxicity of pyridostigmine in rats using a variety of restraint, forced running and forced swimming stress conditions. In this study, we evaluated the effects of sequential pre-exposure to multiple stressors on the acute toxicity of pyridostigmine. Rats (n = 8 per treatment group) were either un-stressed or stressed by restraint (60 min), forced running (60 min, 15 m/min, 6 degrees incline) and forced swimming (15 min), and then given either vehicle (saline, 1 ml/kg, po) or pyridostigmine (30 mg/kg, po) immediately after the final stressor. Functional signs of cholinergic toxicity (involuntary movements, autonomic dysfunction) were recorded at 0.5, 1 and 2 h after dosing. Body temperature was measured both before stress and 2 h after dosing. Rats were sacrificed immediately after 2-h functional observations to collect tissues (whole blood, diaphragm, frontal cortex, hippocampus and cerebellum) for measurement of cholinesterase activity. Stressed rats treated with pyridostigmine exhibited higher lethality (2/8) compared to unstressed rats given pyridostigmine (0/8). Pyridostigmine elicited classical signs of cholinergic toxicity, but the rats that died did not show increased cholinergic signs and no significant differences in cholinergic signs were noted between treatment groups. Cholinesterase activity was significantly inhibited in blood (47-50%) and diaphragm (80%) following pyridostigmine exposure regardless of stress conditions. Slight but significant inhibition (11-15%) of cerebellar cholinesterase activity was observed following pyridostigmine exposure, but inhibition was not influenced by stress. We conclude that while acute lethality from pyridostigmine may be increased by combined, multiple stressors, increased lethality does not appear due to enhanced cholinergic toxicity or via increased cholinesterase inhibition in either central or peripheral tissues.

Animals↗
PubMed2001

Chronic health risks from aggregate exposures to ionizing radiation and chemicals: scientific basis for an assessment framework.

Very little quantitative analysis is currently available on the cumulative effects of exposure to multiple hazardous agents that have either similar or different mechanisms of action. Over the past several years, efforts have been made to develop the methodologies for risk assessment of chemical mixtures, but mixed exposures to two or more dissimilar agents such as radiation and one or more chemical agents have not yet been addressed in any substantive way. This article reviews the current understanding of the health risks arising from mixed exposures to ionizing radiation and specific chemicals. Specifically discussed is how mixed radiation/chemical exposures, when evaluated in aggregation, were linked to chronic health endpoints such as cancer and intermediate health outcomes such as chromosomal aberrations. Also considered is the extent to which the current practices are consistent with the scientific understanding of the health risks associated with mixed-agent exposures. From this the discussion moves to the research needs for assessing the cumulative health risks from aggregate exposures to ionizing radiation and chemicals. The evaluation indicates that essentially no guidance has been provided for conducting risk assessment for two agents with different mechanisms of action (i.e., energy deposition from ionizing radiation versus DNA interactions with chemicals) but similar biological endpoints (i.e., chromosomal aberrations, mutations, and cancer). The literature review also reveals the problems caused by the absence of both the basic science and an appropriate evaluation framework for the combined effects of mixed-agent exposures. This makes it difficult to determine whether there is truly no interaction or somehow the interaction is masked by the scale of effect observation or inappropriate dose-response assumptions.

Animals↗
PubMedDate not supplied

Developing a pesticide policy for individuals with multiple chemical sensitivity: considerations for institutions.

Institutions are increasingly being asked to accommodate individuals with multiple chemical sensitivity (MCS). Most establishments have chosen to provide such accommodations on a case-by-case basis only. This paper investigates feasible actions that may be taken by institutions to reduce exposure of MCS individuals as well as the general institutional population to pesticides and other substances. Emphasis is placed on procedures that can be instituted on a regular basis and may be combined with case-by-case management for better resolution of problems.

Environmental Exposure↗
PubMed2006

Association of allergic rhinitis with pesticide use among grape farmers in Crete, Greece.

OBJECTIVE: To explore the association of allergic rhinitis with the use of pesticides among grape farmers in Crete. METHODS: A cross-sectional study of 120 grape farmers and 100 controls at the Malevisi region in Northern Crete was conducted. The protocol consisted of a questionnaire, skin prick tests for 16 common allergens, measurement of specific IgE antibodies against 8 allergens, and spirometry before and after bronchodilatation. RESULTS: Grape farmers who used pesticides had higher prevalence rates of allergic rhinitis symptoms (OR, 3.0; 95% CI, 1.4 to 6.2) compared with grape farmers who reported no current use of pesticides, and control subjects. Logistic regression models controlling for age, sex and smoking status showed that 6 of the 12 predefined groups of major pesticides were significantly related to allergic rhinitis symptoms. The highest risks were observed for paraquat and other bipyridyl herbicides (OR, 2.2; 95% CI, 1.0 to 4.8), dithiocarbamate fungicides (OR, 2.5; 95% CI, 1.1 to 5.3) and carbamate insecticides (OR, 3.0; 95% CI, 1.4 to 6.5). A factor analysis of pesticides used identified 3 distinct factors. The most common factor was that of multiple pesticide use that included 9 pesticides and was significantly associated with allergic rhinitis (OR, 1.5; 95% CI, 1.0 to 2.3). ORs were higher when allergic rhinitis was defined using both questionnaire data on symptoms and atopy. CONCLUSIONS: Occupational exposure to multiple agricultural chemicals could be related to allergic rhinitis in grape farmers.

Adult↗
PubMed1987

Mortality among flavour and fragrance chemical plant workers in the United States.

Vital status on 1 January 1981 was determined for a cohort of 1412 white men employed in a flavour and fragrance chemical plant between 1945 and 1965 in order to investigate the risks from fatal diseases among men exposed to multiple chemicals in the manufacture of fragrances, flavours, aroma chemicals, and other organic substances. Cause specific standardised mortality ratios (SMRs) were calculated for the entire study population and for several subsets by likelihood of exposure to chemicals, duration of employment, and year of hire. SMRs for rectal cancer and ischaemic heart disease were raised among white male employees whose jobs were in production, maintenance, laboratory, or other jobs that would involve exposure to multiple chemicals used and produced in the plant. The excess of rectal cancer was confined to employees who had worked as chemical operators and mortality was significantly raised among men who worked for ten or more years. Traces of dioxin were recently found in and around plant buildings that used trichlorophenol in the production of hexachlorophene. The study group was small and had limited power to detect excess risk of rare causes of death; however, no soft tissue sarcomas were observed during the study period.

Chemical Industry↗
PubMedDate not supplied

Neurotoxicity in single photon emission computed tomography brain scans of patients reporting chemical sensitivities.

The subset of patients reporting chemical sensitivity with neurocognitive complaints usually exhibits specific abnormalities of brain metabolism consistent with neurotoxicity, on imaging with single photon emission computed tomography (SPECT). These recurrent neurotoxic patterns are characterized by a mismatch in tracer uptake between early- and late-phase imaging, multiple hot and cold foci throughout the cortex, temporal asymmetry and increased tracer uptake into the soft tissues and, sometimes, the basal ganglia. Previous studies confirm these neurotoxic findings in patients with neurotoxic chemical exposures and breast implants. Affective processes such as depression do not, alone, show this pattern. These abnormalities in SPECT images correlate with documented neurocognitive impairment. Controlled challenges to ambient chemicals can induce profound neurotoxic changes seen on SPECT imaging in chemically sensitive patients. Detoxification treatment techniques frequently produce significant improvement on brain SPECT brain imaging in these patients. Neurotoxicity appears to be characteristic in many cases of chemical sensitivity.

Brain↗
PubMed2005

Prior multiple ethanol withdrawals enhance stress-induced anxiety-like behavior: inhibition by CRF1- and benzodiazepine-receptor antagonists and a 5-HT1a-receptor agonist.

Repeated withdrawals from chronic ethanol induce a persistent adaptive change. Further, stress substitutes for the initial two withdrawals of a multiple-withdrawal protocol to sensitize rats to withdrawal-induced anxiety-like behavior ('anxiety'). Therefore, it was tested whether the persistent adaptation induced by multiple-withdrawal exposures allows stress to elicit anxiety after a period of abstinence. Social interaction was used to assess the degree of anxiety induced by 45 min of restraint stress 3, 7, or 14 days after rats were exposed to multiple withdrawals from a chronic 4.5% ethanol diet. Restraint stress reduced social interaction (ie anxiety-like behavior) at 3, but not at 7 or 14 days, after the multiple withdrawals. No anxiety response was observed in animals that received multiple withdrawals without stress or in animals that received stress when exposed only to control liquid diet. Drugs (ie a CRF1-receptor antagonist, a benzodiazepine receptor antagonist, and a 5-HT1A-receptor agonist) previously demonstrated to block the cumulative adaptation, when administered during repeated withdrawals, prevented stress-induced anxiety-like behavior during abstinence. Additionally, these drugs applied prior to stress in the rats previously exposed to the repeated withdrawal protocol, likewise, minimized stress-induced anxiety. The anxiety following stress during abstinence from previous chronic ethanol exposure is indicative of an interaction of stress with the persistent adaptive change caused by repeated withdrawals. Stress eliciting anxiety-like behavior during abstinence from previous ethanol exposures in rats is consistent with stress inducing anxiety during recovery (sobriety) in the alcoholic, a circumstance that can facilitate craving and relapse.

Analysis of Variance↗
PubMed1999

Hyperthermia-enhanced serotonin (5-HT) depletion resulting from D-fenfluramine (D-Fen) exposure does not evoke a glial-cell response in the central nervous system of rats.

D-Fen-induced hyperthermia has been shown to coincide with an enhanced depletion of 5-HT and 5-hydroxyindole acetic acid (5-HIAA). Because these observations have relied on D-Fen exposure at multiple environmental temperatures, some have questioned the validity of the findings. Therefore, this experiment was designed to determine if the correlation between elevated body temperature and 5-HT depletion could be observed when D-Fen exposure occurred in one warm environment (28 degrees C) and to determine if a hyperthermia-enhanced glial-cell response could be evoked by D-Fen exposure. Hyperthermia-enhanced 5-HT and 5-HIAA depletion resulting from D-Fen exposure was dependent on body temperature during drug exposure. In the frontal cortex, 5-HT concentrations ranged from 3 to 45% of control values. Likewise, in the striatum and hippocampus, 5-HT concentrations ranged from 13 to 53% and 6 to 40%, respectively. The 5-HIAA concentrations had a wider range than the 5-HT concentrations for each brain region. In the frontal cortex, striatum and hippocampus, 5-HIAA ranged from 0 to 93%, 15 to 72% and 0 to 83% of control, respectively. In spite of the substantial reductions in 5-HT, there was no detectable glial-cell response. D-Fen-induced hyperthermia does not appear to cause generalized damage to neurons in the frontal cortex, striatum and hippocampus.

Animals↗
PubMed1988

The effect of indomethacin on the psychomotor function of patients with rheumatic diseases.

We have compared the effect of single and multiple doses of indomethacin and placebo on objective measurements of psychomotor impairment in patients. Following a single 50 mg dose (n = 8), indomethacin produced psychomotor disturbance in only those patients who had no recent history of NSAID exposure. After multiple doses of indomethacin (25 and 50 mg tid for 5 days), significant psychomotor impairment was observed. We conclude that other NSAIDs may induce cross-tolerance to the psychomotor effects of indomethacin. Tachyphylaxis may develop to the psychomotor disturbance caused by indomethacin.

Arthritis, Rheumatoid↗
PubMed2005

Prolonged menstrual cycles in female workers exposed to ethylene glycol ethers in the semiconductor manufacturing industry.

BACKGROUND: It has been shown that female workers exposed to ethylene glycol ethers (EGEs) in the semiconductor industry have higher risks of spontaneous abortion, subfertility, and menstrual disturbances, and prolonged waiting time to pregnancy. AIMS: To examine whether EGEs or other chemicals are associated with long menstrual cycles in female workers in the semiconductor manufacturing industry. METHODS: Cross-sectional questionnaire survey during the annual health examination at a wafer manufacturing company in Taiwan in 1997. A three tiered exposure-assessment strategy was used to analyse the risk. A short menstrual cycle was defined to be a cycle less than 24 days and a long cycle to be more than 35 days. RESULTS: There were 606 valid questionnaires from 473 workers in fabrication jobs and 133 in non-fabrication areas. Long menstrual cycles were associated with workers in fabrication areas compared to those in non-fabrication areas. Using workers in non-fabrication areas as referents, workers in photolithography and diffusion areas had higher risks for long menstrual cycles. Workers exposed to EGEs and isopropanol, and hydrofluoric acid, isopropanol, and phosphorous compounds also showed increased risks of a long menstrual cycle. CONCLUSIONS: Exposure to multiple chemicals, including EGEs in photolithography, might be associated with long menstrual cycles, and may play an important role in a prolonged time to pregnancy in the wafer manufacturing industry; however, the prevalence in the design, possible exposure misclassification, and chance should be considered.

Adolescent↗
PubMed2006

Persuasive evidence that formocresol use in pediatric dentistry is safe.

Concern has been expressed about the safety of formocresol use in pediatric dentistry. Formaldehyde, a primary component in formocresol, is a hazardous substance and is considered a probable human carcinogen by Health Canada. However, humans inhale and ingest formaldehyde daily and also produce this compound as part of normal cellular metabolism. The human body is physiologically equipped to handle this exposure through multiple pathways for oxidation of formaldehyde to formate and incorporation into biological macromolecules via tetrahydrofolate-dependent one-carbon biosynthetic pathways. Recent re-evaluation of earlier research that examined potential health risks associated with formaldehyde exposure has shown that the research was based on flawed assumptions, which resulted in erroneous conclusions. This review examines more recent research about formaldehyde metabolism, pharmacokinetics and carcinogenicity, the results of which indicate that formaldehyde is probably not a potent human carcinogen under conditions of low exposure. Extrapolation of these research results to pediatric dentistry suggests an inconsequential risk of carcinogenesis associated with formaldehyde use in pediatric pulp therapy. Areas for further investigation are suggested.

Animals↗
PubMed2004

Baseline measurements of smoke exposure among wildland firefighters.

Extensive measurements of smoke exposure among wildland firefighters are summarized, showing that firefighters can be exposed to significant levels of carbon monoxide and respiratory irritants, including formaldehyde, acrolein, and respirable particulate matter. Benzene was also measured and found to be well below permissible exposure limits, with the highest concentrations occurring among firefighters working with engines and torches burning petroleum-based fuel. Exposures to all pollutants were higher among firefighters at prescribed burns than at wildfires, while shift-average smoke exposures were lowest among firefighters who performed initial attack of wildfires in the early stages of the fires. Smoke exposure reaches its highest levels among firefighters maintaining fire within designated firelines and performing direct attack of spot fires that cross firelines. These events and the associated smoke exposures were positively correlated with increasing ambient wind speeds, which hamper fire management and carry the convective plume of the fire into firefighters' breathing zone. The pollutants measured in smoke were reasonably well-correlated with each other, enabling estimation of exposure to multiple pollutants in smoke from measurements of a single pollutant such as carbon monoxide.

Air Pollutants↗
PubMed2004

Reducing attenuation in exposure-response relationships by exposure modeling and grouping: the relationship between wood dust exposure and lung function.

BACKGROUND: In a study of wood dust exposure and lung function, we tested the effect on the exposure-response relationship of six different exposure metrics using the mean measured exposure of each subject versus the mean exposure based on various methods of grouping subjects, including job-based groups and groups based on an empirical model of the determinants of exposure. METHODS: Multiple linear regression was used to examine the association between wood dust concentration and forced expiratory volume in 1s (FEV(1)), adjusting for age, sex, height, race, pediatric asthma, and smoking. RESULTS: Stronger point estimates of the exposure-response relationships were observed when exposures were based on increasing levels of aggregation, allowing the relationships to be found statistically significant in four of the six metrics. The strongest point estimates were found when exposures were based on the determinants of exposure model. CONCLUSIONS: Determinants of exposure modeling offers the potential for improvement in risk estimation equivalent to or beyond that from job-based exposure grouping.

Adolescent↗
PubMed1995

Stress-induced atrophy of apical dendrites of hippocampal CA3c neurons: comparison of stressors.

Repeated restraint stress induces an atrophy of apical dendrites of CA3c pyramidal neurons in the hippocampus, but the relationship between stress and adrenocortical activation has not been thoroughly investigated. In order to better understand the relationship between neural and non-neural indices of the severity of stress, we investigated the temporal relationship between CA3c dendritic atrophy and indices of adrenal steroid stress responsiveness. For this purpose, we used two different stress regimens: repeated restraint stress (6 h/day) and a chronic multiple stress paradigm (shaking, restraint and swimming, each day), differing in the degree of adrenal activation produced over 14 and 21 days. Atrophy of dendrites of CA3c neurons was found after 21 days of stress, but not after 14 days, and was of a similar magnitude for both stressors. However, non-neural measures differed between the two stress paradigms: (i) chronic restraint stress caused a significant habituation by day 21 in the corticosterone response to acute restraint, whereas chronic multiple stress exposure was not accompanied by habituation of the corticosterone response to restraint; (ii) chronic restraint stress caused neither adrenal hypertrophy nor thymus atrophy, but did reduce the rate of body weight gain throughout the 21 days, whereas chronic multiple stress caused a transient adrenal hypertrophy (on day 14), delayed suppression of thymus weight (on day 21) and transient reduction of body weight gain (on days 7 and 14, but not on day 21). Thus the non-neural indices of response to stress--although complex in their time course--suggest that the multiple stress regimen is a somewhat more potent chronic stressor for corticosterone and adrenal responses. Yet both stress regimens produced the same degree of apical dendritic atrophy in CA3c pyramidal neurons. These results are consistent with a model in which adrenocortical secretion plays a permissive role in enabling another agent, namely, excitatory amino acids, to produce the final effect.

Animals↗
PubMed2000

Repeated cadmium exposures enhance the malignant progression of ensuing tumors in rats.

Prior studies show that a single subcutaneous (sc) exposure to cadmium (Cd) will induce injection site sarcomas (ISS) in rats. These tumors, thought clearly malignant, do not often metastasize or invade subdermal muscle layers because of their location. Recent evidence indicates that when tumorigenic cells chronically exposed to Cd in vitro are inoculated into mice, tumor progression and invasiveness in the mice are enhanced. Thus, we studied the effects of repeated Cd exposures on tumor incidence, progression, and metastatic potential in rats. Wistar (WF) and Fischer (F344) rats (30 per group) were injected sc in the dorsal thoracic midline with CdCl2 once weekly for 18 weeks with doses of 0, 10, 20, or 30 micromol Cd/kg. This resulted in total doses of 0, 180, 360, or 540 micromol/kg. One other group of each strain received a low, loading dose of Cd (3 micromol/kg) prior to 17 weekly injections of 30 micromol/kg (total dose 513 micromol/kg). Rats were observed for 2 years. Many F344 rats (57%) died within one week after the first injection of the highest dose, but WF rats were not affected. The low loading dose prevented acute lethality of the high dose in F344 rats. Surprisingly, latency (time to death by tumor) of ISS was the shortest in the groups given the low loading dose in both strains. ISS in these groups also showed the highest rate of metastasis and subdermal muscle layer invasion. Based on ISS incidence in the groups given the lowest total dose of Cd (180 micromoles/kg), F344 rats were more sensitive to tumor induction, showing an incidence of 37% compared to 3% in WF rats. On the other hand, Cd-induced ISS showed a higher overall metastatic rate in WF rats (18 metastatic ISS/68 total tumors in all treated groups; 27%) compared to F344 rats (6%). Immunohistochemically, the primary ISS showed high levels of metallothionein (MT), a cadmium-binding protein, while metastases were essentially devoid of MT. These results indicate that repeated Cd exposures more rapidly induce ISS. An initial low exposure to Cd further accelerates the appearance and enhances the metastatic potential and invasiveness of these tumors. The primary and metastatic ISS appear to have a differing phenotype, at least with regard to MT production. The association between multiple Cd exposures and enhanced metastatic potential of the ensuing tumors may have important implications in chronic exposures to Cd, or in cases of co-exposure of Cd with organic carcinogens, as in tobacco smoking.

Animals↗
PubMed1996

Reproductive and developmental effects of disinfection by-products in drinking water.

Recent epidemiologic studies have reported associations between the consumption of chlorinated drinking water and reproductive and developmental effects. Here we review the available epidemiologic data, assess the hazard potential posed by exposure to disinfection by-products, identify critical data gaps, and offer recommendations for further research. The epidemiologic evidence supporting associations between exposure to water disinfection by-products (DBPs) and adverse pregnancy outcomes is sparse, and positive findings should be interpreted cautiously. The methods used during the early stages of research in this area have been diverse. Variability in exposure assessment and endpoints makes it difficult to synthesize or combine the available data. Exposure misclassification and unmeasured confounding may have lead to bias in risk estimation. Future studies of reproductive outcome and exposure to chlorinated water should use improved methods for exposure assessment to 1) assure selection of appropriate exposure markers, 2) assess seasonal and annual fluctuations in DBPs, 3) assess variability within the distribution system, and 4) assess exposure through multiple routes such as bathing and showering, as well as consumption. Population-based studies should be conducted to evaluate male and female fertility, conception delay, growth retardation, and specific birth defects. The reproductive and developmental effects of exposure to DBPs could be efficiently explored in ongoing investigations by incorporating valid exposure markers and relevant questionnaire information. Future studies should make use of naturally occurring variability in the concentrations of DBPs and may incorporate biomarkers of exposure and effect in their design. Epidemiologic investigations should be conducted in parallel with laboratory-based and animal studies in a coordinated, multidisciplinary approach.

Abnormalities, Drug-Induced↗
PubMed1976

Passive immunization against exposure to hepatitis B virus in the military: potential and possibilities.

The value of standard γ-globulin with a low titer of antibody to hepatitis B surface antigen (anti-HB(s)) vs hepatitis B immune globulin (HBIG) in prevention of icteric hepatitis B in the military is unclear. Although recent studies have shown a decrease in icteric hepatitis after administration of both types of γ-globulin in populations where acquisition of hepatitis B virus (HBV) is most likely the result of nonparenteral transmission, the data pertaining to parenteral exposure suggest that HBIG delays the incubation period of HBV and decreases the development of passive-active immunity. Since no studies have demonstrated efficacy of standard γ-globulin or HBIG in a drug-using population where multiple HBV exposures are likely, the results observed in most trials are not comparable to hepatitis B associated with drug abuse in the military. Therefore, before a recommendation for use of routine γ-globulin or HBIG can be made for drug-related hepatitis in the military, efficacy of standard γ-globulin and/or HBIG should be demonstrated in this population.

Hepatitis B↗
PubMedDate not supplied

A school-based strategy to assess children's environmental exposures and related health effects in economically disadvantaged urban neighborhoods.

The School Health Initiative: Environment, Learning, Disease (SHIELD) study is a novel school-based investigation of children's environmental health in economically disadvantaged urban neighborhoods of Minneapolis. This article describes the study design and summarizes lessons learned about recruiting and monitoring this historically understudied population. The SHIELD study focused on measuring children's exposures to multiple environmental stressors [volatile organic chemicals (VOCs), environmental tobacco smoke, allergens, bioaerosols, metals, pesticides, polychlorinated biphenyls (PCB), phthalates] and exploring related effects on respiratory health (e.g., lung function) and learning outcomes (e.g., standardized test scores, academic achievement). It involved intensive exposure monitoring, including environmental measurements inside and outside the children's schools and inside their homes, personal measurements with passive dosimeters worn by the children, and biological marker measurements in blood and urine. The SHIELD participants comprised a stratified random sample of 153 "index" children and 51 of their siblings enrolled in grades 2-5 at two adjacent elementary schools. The Minneapolis Public Schools (MPS) assisted with identifying, contacting, recruiting, and monitoring this population, which traditionally is difficult to study because families/children are highly mobile, speak a diversity of languages, frequently do not have a telephone, endure economic hardships, often do not trust researchers, and have a spectrum of unconventional lifestyles and living arrangements. Using a school-based approach, the overall SHIELD enrollment (response) rate was 56.7%, with a wide disparity between English-speaking (41.7%) and non-English-speaking (71.0%) families/children. Most children remained involved in the study through both monitoring sessions and exhibited an acceptable degree of compliance with study protocols, including providing blood and urine samples. Results indicate that it is both practical and affordable to conduct probability-based exposure studies in this population, but that it is also important to improve our understanding of factors (e.g., cultural, economic, psychological, social) affecting the willingness of families/children to participate in such studies, with special emphasis on developing cost-effective recruitment methods.

Air Pollution, Indoor↗