Esterase-Triggered Self-Immolative Thiocarbamates Provide Insights into COS Cytotoxicity.

Hydrogen sulfide (H2S) is an important gasotransmitter and biomolecule, and many synthetic small-molecule H2S donors have been developed for H2S-related research. One important class of triggerable H2S donors is self-immolative thiocarbamates, which function by releasing carbonyl sulfide (COS), which is rapidly converted to H2S by the ubiquitous enzyme carbonic anhydrase (CA). Prior studies of esterase-triggered thiocarbamate donors reported significant inhibition of mitochondrial bioenergetics and toxicity when compared to direct sulfide donors, suggesting that COS may function differently than H2S. Here, we report a suite of modular esterase-triggered self-immolative COS donors and include the synthesis, H2S release profiles, and cytotoxicity of the developed donors. We demonstrate that the rate of ester hydrolysis correlates directly with the observed cytotoxicity in cell culture, which further supports the hypothesis that COS functions as more than a simple H2S shuttle in certain biological systems.

A Global Perspective on Sulfur Oxide Controls in Coal-Fired Power Plants and Cardiovascular Disease.

Sulfur oxides (SOx), particularly SO2 emitted by coal-fired power plants, produce long-term risks for cardiovascular disease (CVD). We estimated the relative risks of CVD and ischemic heart disease (IHD) attributable to SOx emission globally. National SOx reduction achieved by emissions control systems was defined as the average SOx reduction percentage weighted by generating capacities of individual plants in a country. We analyzed the relative risk of CVD incidence associated with national SOx reduction for 13,581 coal-fired power-generating units in 79 countries. A 10% decrease in SOx emission was associated with 0.28% (males; 95%CI = -0.39%~0.95%) and 1.69% (females; 95%CI = 0.99%~2.38%) lower CVD risk. The effects on IHD were > 2 times stronger among males than females (2.78%, 95%CI = 1.99%~3.57% vs. 1.18%, 95%CI = 0.19%~2.17%). Further, 1.43% (males) and 8.00% (females) of CVD cases were attributable to suboptimal SOx reduction. Thus, enhancing regulations on SOx emission control represents a target for national and international intervention to prevent CVD.

Mass spectrometric analysis of rat cerebrospinal fluid proteins following exposure to the neurotoxicant carbonyl sulfide.

RATIONALE: Using a proteomic-based approach we have investigated possible altered expression of a range of cerebral spinal fluid (CSF) proteins following exposure to the neurotoxicant carbonyl sulfide (COS). CSF is ideal for the investigation of markers of brain injury or disease since it is secreted from several central nervous system structures and changes in the CSF composition may reflect brain insult and many pathological processes. METHODS: Animals were placed in exposure chambers and were exposed to 0 ppm or 500 ppm COS for 1, 2 or 3 days, 6 h per day. After the last inhalation exposure, 50-70 µL CSF sample was obtained by lumbar puncture. CSF samples were analyzed by electrospray ionization mass spectrometry (ESI-MS) on either a Premier quadrupole time-of-flight (QTOF) or an Agilent 6340 ion trap and by matrix-assisted laser desorption/ionization (MALDI)-MS on a 4800 MALDI-TOF/TOF analyzer. RESULTS: The dynamic range of abundance of the identified proteins spanned over more than three orders of magnitude. The four most abundant proteins identified (albumin, cystatin C, serotransferrin, transthyretin) are major proteins that are present in both CSF and blood at high levels but the fifth most abundant protein identified (prostaglandin H2D isomerase) is the second most abundant protein in human CSF and is secreted and synthesized in the rat central nervous system. No significant differences were observed between COS-treated CSF samples and the control CSF samples because of blood contamination. CONCLUSIONS: Quantitative MS protein analyses of rat CSF is limited by the low sample volumes that can practicably be obtained from rats and the low protein concentrations in rat CSF. Results of this work suggest a clear need for CSF collection that would minimize blood contamination. Published in 2014. This article is a U.S. Government work and is in the public domain in the USA.

Sulfite-mediated oxidation of myeloperoxidase to a free radical: immuno-spin trapping detection in human neutrophils.

Previous studies focused on catalyzed oxidation of (bi)sulfite, leading to the formation of the reactive sulfur trioxide ((•)SO3(-)), peroxymonosulfate ((-)O3SOO(•)), and sulfate (SO4(•-)) anion radicals, which can damage target proteins and oxidize them to protein radicals. It is known that these very reactive sulfur- and oxygen-centered radicals can be formed by oxidation of (bi)sulfite by peroxidases. Myeloperoxidase (MPO), an abundant heme protein secreted from activated neutrophils that play a central role in host defense mechanisms, allergic reactions, and asthma, is a likely candidate for initiating the respiratory damage caused by sulfur dioxide. The objective of this study was to examine the oxidative damage caused by (bi)sulfite-derived free radicals in human neutrophils through formation of protein radicals. We used immuno-spin trapping and confocal microscopy to study the protein oxidations driven by sulfite-derived radicals. We found that the presence of sulfite can cause MPO-catalyzed oxidation of MPO to a protein radical in phorbol 12-myristate 13-acetate-activated human neutrophils. We trapped the MPO-derived radicals in situ using the nitrone spin trap 5,5-dimethyl-1-pyrroline N-oxide and detected them immunologically as nitrone adducts in cells. Our present study demonstrates that myeloperoxidase initiates (bi)sulfite oxidation leading to MPO radical damage, possibly leading to (bi)sulfite-exacerbated allergic reactions.

Proteomic analysis of Alternaria alternata (Fr.) Keissler responds to COS fumigation.

Carbonyl sulfide (COS) is a new fumigant which has been a potential alternative to methyl bromide and phosphine in many applications. In this study, we investigated the fungitoxicity of COS towards the pathogen of pear black spot disease Alternaria alternata (Fr.) Keissler (A. alternata). Moreover, proteomic analysis and RT-PCR was performed and our results showed that during the fumigation, the regulation of 21 proteins in protein expression and mRNA accumulation levels is involved, which respond to growth inhibition caused by COS. These results provide new clues for the mechanism of the fungitoxicity of COS.

Gene expression studies reveal that DNA damage, vascular perturbation, and inflammation contribute to the pathogenesis of carbonyl sulfide neurotoxicity.

Carbonyl sulfide (COS) is an odorless gas that produces highly reproducible lesions in the central nervous system. In the present study, the time course for the development of the neurotoxicological lesions was defined and the gene expression changes occurring in the posterior colliculus upon exposure to COS were characterized. Fischer 344 rats were exposed to 0 or 500 ppm COS for one, two, three, four, five, eight, or ten days, six hours per day. On days 1 and 2, no morphological changes were detected; on day 3, 10/10 (100%) rats had necrosis in the posterior colliculi; and on day 4 and later, necrosis was observed in numerous areas of the brain. Important gene expression changes occurring in the posterior colliculi after one or two days of COS exposure that were predictive of the subsequent morphological findings included up-regulation of genes associated with DNA damage and G1/S checkpoint regulation (KLF4, BTG2, GADD45g), apoptosis (TGM2, GADD45g, RIPK3), and vascular mediators (ADAMTS, CTGF, CYR61, VEGFC). Proinflammatory mediators (CCL2, CEBPD) were up-regulated prior to increases in expression of the astrocytic marker GFAP and macrophage marker CSF2rb1. These gene expression findings were predictive of later CNS lesions caused by COS exposure and serve as a model for future investigations into the mechanisms of disease in the central nervous system.

Inhalational exposure to carbonyl sulfide produces altered brainstem auditory and somatosensory-evoked potentials in Fischer 344N rats.

Carbonyl sulfide (COS), a chemical listed by the original Clean Air Act, was tested for neurotoxicity by a National Institute of Environmental Health Sciences/National Toxicology Program and U.S. Environmental Protection Agency collaborative investigation. Previous studies demonstrated that COS produced cortical and brainstem lesions and altered auditory neurophysiological responses to click stimuli. This paper reports the results of expanded neurophysiological examinations that were an integral part of the previously published experiments (Morgan et al., 2004, Toxicol. Appl. Pharmacol. 200, 131-145; Sills et al., 2004, Toxicol. Pathol. 32, 1-10). Fisher 334N rats were exposed to 0, 200, 300, or 400 ppm COS for 6 h/day, 5 days/week for 12 weeks, or to 0, 300, or 400 ppm COS for 2 weeks using whole-body inhalation chambers. After treatment, the animals were studied using neurophysiological tests to examine: peripheral nerve function, somatosensory-evoked potentials (SEPs) (tail/hindlimb and facial cortical regions), brainstem auditory-evoked responses (BAERs), and visual flash-evoked potentials (2-week study). Additionally, the animals exposed for 2 weeks were examined using a functional observational battery (FOB) and response modification audiometry (RMA). Peripheral nerve function was not altered for any exposure scenario. Likewise, amplitudes of SEPs recorded from the cerebellum were not altered by treatment with COS. In contrast, amplitudes and latencies of SEPs recorded from cortical areas were altered after 12-week exposure to 400 ppm COS. The SEP waveforms were changed to a greater extent after forelimb stimulation than tail stimulation in the 2-week study. The most consistent findings were decreased amplitudes of BAER peaks associated with brainstem regions after exposure to 400 ppm COS. Additional BAER peaks were affected after 12 weeks, compared to 2 weeks of treatment, indicating that additional regions of the brainstem were damaged with longer exposures. The changes in BAERs were observed in the absence of altered auditory responsiveness in FOB or RMA. This series of experiments demonstrates that COS produces changes in brainstem auditory and cortical somatosensory neurophysiological responses that correlate with previously described histopathological damage.

Air pollution and cardiovascular health in Mandi-Gobindgarh, Punjab, India - a pilot study.

Large number of epidemiological studies to know the effect of air pollution on the general mortality and morbidity, and the cardiopulmonary morbidity and mortality are concentrated in USA and Europe. Regional differences in air pollution necessitate regional level health effects studies. Present study is a cross sectional pilot study from India, an Asian country. A sample of population from an industrial town 'Mandi Gobindgarh' and a nonindustrial town 'Morinda' were selected. A cross-sectional household survey was done in both the towns. One hundred subjects were selected from each of the towns. Ambient air quality data was collected for both towns over a period of 10-months to assess seasonal variations. In the present study the average PM10 (particulate matter with < or = 10 microm aerodynamic diameter) levels in Morinda were 99.54 microg/m3 and in Mandi Gobindgarh 161.20 microg/m3. As per NAAQS the permitted levels of PM10 is 50 microg/m3 taken as annual average (arithmetic mean). Elemental analysis of the aerosol samples found the concentration levels to be higher in Mandi- Gobindgarh than Morinda. The population in Gobindgarh shows a higher prevalence of symptoms of angina and cardiovascular disease considered in the study as compared to Morinda. When the same data is viewed in terms of male and female population, the female population is found to show these symptoms marginally higher than their counterparts. Considering the results of present study it can be stated that the increased levels of different pollutants and the higher prevalence of cardiovascular symptoms in Mandi-Gobindgarh (Industrial town) than the Morinda (Non-Industrial town) is because of the association of PM pollution with cardiovascular diseases. Keeping in view the current status of literature, further studies in this direction are needed in a country like India. Such data will also be globally relevant.

Review of the toxicology of carbonyl sulfide, a new grain fumigant.

Carbonyl sulfide (COS) is a new grain fumigant which has been developed to replace methyl bromide, being phased out due to its ozone depletion properties, and to supplement phosphine gas which is experiencing increased insect resistance. Treatment of commodities with COS, a highly effective fumigant, results in residues that are near or indistinguishable to natural background levels of this compound. COS is a naturally occurring gas, being the predominant sulfur moiety in the atmosphere, occurs naturally in food and is a normal by-product of mammalian aerobic metabolism. COS has low acute inhalational toxicity but with a steep dose response curve; COS is neither genotoxic nor a developmental toxicant but does reversibly impair male fertility. Prolonged, repeated exposure to COS is likely to present similar neurotoxicity hazards to that of the structurally and toxicologically related compound carbon disulfide. Although the occupational risks presented by COS as a fumigant of bulk grain are significant, these are, as they have been for a considerable time for phosphine and methyl bromide, manageable by good occupational safety practices. Consideration may need to be given to scrubbing of ventilated COS and its breakdown product hydrogen sulfide, at the completion of fumigation to minimise worker and bystander exposure. In terms of classical regulatory toxicology studies, the available database for COS is deficient in many aspects and registration in most jurisdictions will depend on sound scientific argument built upon the totality of the existing scientific data as there are strong arguments supporting the registration of this compound.

Interdisciplinary neurotoxicity inhalation studies: carbon disulfide and carbonyl sulfide research in F344 rats.

Inhalation studies were conducted on the hazardous air pollutants, carbon disulfide, which targets the central nervous system (spinal cord) and peripheral nervous system (distal portions of long myelinated axons), and carbonyl sulfide, which targets the central nervous system (brain). The objectives were to investigate the neurotoxicity of these compounds by a comprehensive evaluation of function, structure, and mechanisms of disease. Through interdisciplinary research, the major finding in the carbon disulfide inhalation studies was that carbon disulfide produced intra- and intermolecular protein cross-linking in vivo. The observation of dose-dependent covalent cross-linking in neurofilament proteins prior to the onset of lesions is consistent with this process contributing to the development of the neurofilamentous axonal swellings characteristic of carbon disulfide neurotoxicity. Of significance is that valine-lysine thiourea cross-linking on rat globin and lysine-lysine thiourea cross-linking on erythrocyte spectrin reflect cross-linking events occurring within the axon and could potentially serve as biomarkers of carbon disulfide exposure and effect. In the carbonyl sulfide studies, using magnetic resonance microscopy (MRM), we determined that carbonyl sulfide targets the auditory pathway in the brain. MRM allowed the examination of 200 brain slices and made it possible to identify the most vulnerable sites of neurotoxicity, which would have been missed in our traditional neuropathology evaluations. Electrophysiological studies were focused on the auditory system and demonstrated decreases in auditory brain stem evoked responses. Similarly, mechanistic studies focused on evaluating cytochrome oxidase activity in the posterior colliculus and parietal cortex. A decrease in cytochrome oxidase activity was considered to be a contributing factor to the pathogenesis of carbonyl sulfide neurotoxicity.

Carbonic anhydrase metabolism is a key factor in the toxicity of CO2 and COS but not CS2 toward the flour beetle Tribolium castaneum [Coleoptera: Tenebrionidae].

The analogues carbon dioxide (CO(2)), carbonyl sulfide (COS) and carbon disulfide (CS(2)) have been useful as substrate probes for enzyme activities. Here we explored the affinity of the enzyme carbonic anhydrase for its natural substrate CO(2), as well as COS and CS(2) (1) by in vitro kinetic metabolism studies using pure enzyme and (2) through mortality bioassay of insects exposed to toxic levels of each of the gases during carbonic anhydrase inhibition. Hydrolysis of COS to form hydrogen sulfide was catalysed rapidly showing parameters K(m) 1.86 mM and K(cat) 41 s(-1) at 25 degrees C; however, the specificity constant (K(cat)/K(m)) was 4000-fold lower than the reported value for carbonic anhydrase-catalysed hydration of CO(2). Carbonic anhydrase-mediated CS(2) metabolism was a further 65,000-fold lower than COS. Both results demonstrate the deactivating effect toward the enzyme of sulfur substitution for oxygen in the molecule. We also investigated the role of carbonic anhydrases in CO(2), COS and CS(2) toxicity using a specific inhibitor, acetazolamide, administered to Tribolium castaneum (Herbst) larvae via the diet. CO(2) toxicity was greatly enhanced by up to seven-fold in acetazolamide-treated larvae indicating that carbonic anhydrases are a key protective enzyme in elevated CO(2) concentrations. Conversely, mortality was reduced by up to 12-fold in acetazolamide-treated larvae exposed to COS due to reduced formation of toxic hydrogen sulfide. CS(2) toxicity was unaffected by acetazolamide. These results show that carbonic anhydrase has a key role in toxicity of the substrates CO(2) and COS but not CS(2), despite minor differences in chemical formulae.

Contribution of magnetic resonance microscopy in the 12-week neurotoxicity evaluation of carbonyl sulfide in Fischer 344 rats.

In this carbonyl sulfide (COS) study, magnetic resonance microscopy (MRM) and detailed light microscopic evaluation effectively functioned in parallel to assure that the distribution and degree of pathology in the brain was accurately represented. MRM is a powerful imaging modality that allows for excellent identification of neuroanatomical structures coupled with the ability to acquire 200 or more cross-sectional images of the brain, and the ability to display them in multiple planes. F344 rats were exposed to 200-600 ppm COS for up to 12 weeks. Prior to MRM, rats were anesthetized and cardiac perfused with McDowell Trump's fixative containing a gadolinium MR contrast medium. Fixed specimens were scanned at the Duke Center for In Vivo Microscopy on a 9.4 Tesla magnetic resonance system adapted explicitly for microscopic imaging. An advantage of MRM in this study was the ability to identify lesions in rats that appeared clinically normal prior to sacrifice and the opportunity to identify lesions in areas of the brain which would not be included in conventional studies. Other advantages include the ability to examine the brain in multiple planes (transverse, dorsal, sagittal) and obtain and save the MRM images in a digital format that allows for postexperimental data processing and manipulation. MRM images were correlated with neuroanatomical and neuropathological findings. All suspected MRM images were compared to corresponding H&E slides. An important aspect of this study was that MRM was critical in defining our strategy for sectioning the brain, and for designing mechanistic studies (cytochrome oxidase evaluations) and functional assessments (electrophysiology studies) on specifically targeted anatomical sites following COS exposure.

Neurotoxicity of carbonyl sulfide in F344 rats following inhalation exposure for up to 12 weeks.

Carbonyl sulfide (COS), a high-priority Clean Air Act chemical, was evaluated for neurotoxicity in short-term studies. F344 rats were exposed to 75-600 ppm COS 6 h per day, 5 days per week for up to 12 weeks. In rats exposed to 500 or 600 ppm for up to 4 days, malacia and microgliosis were detected in numerous neuroanatomical regions of the brain by conventional optical microscopy and magnetic resonance microscopy (MRM). After a 2-week exposure to 400 ppm, rats were evaluated using a functional observational battery. Slight gait abnormality was detected in 50% of the rats and hypotonia was present in all rats exposed to COS. Decreases in motor activity, and forelimb and hindlimb grip strength were also detected. In rats exposed to 400 ppm for 12 weeks, predominant lesions were in the parietal cortex area 1 (necrosis) and posterior colliculus (neuronal loss, microgliosis, hemorrhage), and occasional necrosis was present in the putamen, thalamus, and anterior olivary nucleus. Carbonyl sulfide specifically targeted the auditory system including the olivary nucleus, nucleus of the lateral lemniscus, and posterior colliculus. Consistent with these findings were alterations in the amplitude of the brainstem auditory evoked responses (BAER) for peaks N3, P4, N4, and N5 that represented changes in auditory transmission between the anterior olivary nucleus to the medial geniculate nucleus in animals after exposure for 2 weeks to 400 ppm COS. A concentration-related decrease in cytochrome oxidase activity was detected in the posterior colliculus and parietal cortex of exposed rats as early as 3 weeks. Cytochrome oxidase activity was significantly decreased at COS concentrations that did not cause detectable lesions, suggesting that disruption of the mitochondrial respiratory chain may precede these brain lesions. Our studies demonstrate that this environmental air contaminant has the potential to cause a wide spectrum of brain lesions that are dependent on the degree and duration of exposure.

Occupational exposures to acid mists and gases and ulcerative lesions of the oral mucosa.

BACKGROUND: This study examines the hypothesis that acid mist or mixtures of acid mists and acid gases are associated with ulcerative lesions of the oral mucosa. METHODS: All 665 active male workers of a metal processing factory were the study population. Semi-quantitative measures of exposure were estimated from a job exposure matrix constructed with industrial hygienist scoring and job titles. Ulcerative lesions of the oral mucosa were identified with standardized clinical dental exams. RESULTS: Past exposure to acid mists were positively associated with ulcerative lesions of the oral mucosa but only among workers without lip sealing (age- and alcohol consumption-adjusted prevalence ratio (PR), PR(adjusted) = 3.40; 90% CI: 1.48-7.85). Also in this worker group, the mixture of acid mists and acid gases was associated with ulcerative lesions of the oral mucosa limited to exposure in the past (PR(adjusted) = 2.83; 90% CI: 1.12-7.17). CONCLUSIONS: There is a positive association between acid mist or mixtures of acid mists and acid gases and ulcerative lesions of the oral mucosa only in the absence of lip sealing. The evidence of a chronic rather than acute irritative process suggests a possible step on the etiology of oral malignancies, which needs investigation.

8-Hydroxy-2'-deoxyguanosine formation and DNA damage induced by sulfur trioxide anion radicals.

The 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation and DNA damage by sulfur trioxide anion radicals (SO3.-) were investigated using ESR spin trapping, HPLC, and electrophoretic assays. Sulfite (SO3(2-) autoxidation generated both hydroxyl (.OH) and SO3.- radicals. Oxidation of SO3(2-) by chromium (VI) generated only SO3.- with much enhanced yield. Incubation of 2'-deoxyguanosine (dG) with SO3(2-) generated 8-OHdG albeit at low yield. Chromium (VI) enhanced the yield four-fold. Electrophoretic assays showed that SO3.- radicals generated by chromium (VI) oxidation of SO3(2-) caused DNA double strand breaks. The results demonstrate that SO3.- radicals are capable of causing dG hydroxylation and DNA double strand breaks.

Morphologic effects of a sulfur(IV) aerosol on the nasal cavity of beagle dogs.

Morphologic changes were observed in nasal cavities of beagle dogs after long-term exposure to a respirable sulfur(IV) aerosol at a concentration equivalent to a sulfur dioxide (SO2) concentration of 0.6 mg/m3. The changes were characterized by a thickened epithelial layer resulting from epithelial proliferation, by a loss of secretory material, and by moderate mononuclear cell infiltration.

[Lung compliance in relation to frequency-dependent compliance (FDC) in men exposed to mixed air pollution]. / Przydatnosc dynamiczna zalezna od czestosci oddechów (FDC) u mezczyzn narazonych na mieszane zanieczyszczenia powietrza.

53 males (age 36.8 +/- 7.2 years) with occupational exposure to atmospheric pollutants (low content of silica, sulfur oxides, carbon oxide and heavy metals) for a mean duration of 12.1 +/- 4.8 years were studied. The majority smoked. Dynamic compliance was calculated from esophageal pressure measurements using an esophageal balloon with an electronic transducer and plethysmographic thoracic volume values (Siregnost FD 88 and FD 91S--Siemens). Dynamic compliance (Cdyn) was registered at a ventilatory rate of 15, 30 and 60/min. A significant correlation was found between Cdyn and ventilatory rate in the examined patients in comparison with the control. Cdyn15 = 73.3 +/- 18.8% Cst, Cdyn30 = 54.6 +/- 18.8% Cst, Cdyn60 = 37.4 +/- 14.9% Cst (control Cdyn15 = 85.17% Cst, p < 0.005, Cdyn30 = 82.6 +/- 11.4% Cst, p < 0.001, Cdyn60 = 67.4 +/- 15.8% Cst, p < 0.001). The percentage of abnormal individual Cdyn60 values in the studied group was significantly higher in comparison with the control (p < 0.005). The decrease of Cdyn60 was related to duration of occupational exposure, to mixed atmospheric pollution and history of smoking.

Pathologic response of the lung to irritant gases.

The pathologic response of the lung to irritant gases ranges from the acute exudative phase through the subacute proliferative phase to the chronic fibrosing phase. These responses are based on damage to the Type I cells, and possibly endothelial cells, and the subsequent proliferative and repair processes in the surviving animals. Responses to high dose exposures appear at the microscopic level as exudation of protein rich fluids into alveoli (alveolar edema) and subsequent death due to anoxia. Physiologically, this could be described as a mismatch of ventilation with perfusion, resulting in impaired gas exchange. Animals surviving this acute exudative phase resolve the alveolar edema to fibrin, and Type II cells become hypertrophic and hyperplastic in the process of replacing the damaged Type I cells. The acute and subacute responses also elicit inflammatory changes in the interstitium of the lung that may progress to fibrosis in the chronic stage of a survivable exposure. Diagnostic cases in livestock involving irritant gases reflect similar toxic injuries to the lung.

Urban air pollution in Latin America and the Caribbean: health perspectives.

In the last few years, air pollution has become a major issue in some countries of Latin America and the Caribbean because of urban development and growing industrialization. In addition to industrial processes often concentrated in the cities, vehicle emission and stationary-source fuel combustion are the primary sources of air pollution. Although air-quality standards have been established in some Latin American countries, these are frequently exceeded. Adverse health effects of air pollution have been mainly associated with the following pollutants: sulfur dioxide and particulate matter, photochemical oxidants, nitrogen dioxide and carbon monoxide, and lead. Short-term as well as long-term effects can be expected at levels exceeding WHO guidelines. The Latin American urban areas most affected by anthropogenic pollutant emissions are: the area of São Paulo (Brazil), the city of Santiago (Chile) and the metropolitan area of Mexico City. However, situations similar to those prevailing in these cities could well occur in other cities of Latin America and the Caribbean. The population exposed to air-pollutant levels exceeding WHO guidelines can be estimated to 81 million or 26.5% of the total urban population of Latin America and 19% of its total population. These estimates correspond to 30 million children (0-14), 47 million adults (15-59) and 4 million elderly people (60+). To date a very limited number of epidemiological studies have been carried out to determine the potential health effects of air pollutants in Latin America. To obtain a rough estimate, a scenario was hypothesized in which subjects living in cities would be exposed to a given level of air pollutant, using data from the international literature to extrapolate the expected number of events in different strata of the hypothetical population. The estimated health effects are considerable and warrant priority control intervention. This is true although epidemiological studies are needed to evaluate the health impact of specific pollutant compounds as well as their interactions in Latin American populations exposed to high levels of pollution.

Urban air pollution in Latin America and the Caribbean: health perspectives

In the last few years, air pollution has become a major issue in some countries of Latin America and the Caribbean because of urben development and growing industrialization. In addition to industrial processes often concentrated in the cities, vehicle emission and stationary-source fuel combustion are the primary source of air pollution. Although air-quality standards have been established in some Latin American countries, these are frequently exceeded. Adverse health effects of air pollution have been mainly associated with the following pollutants: sulfur dioxide and pariculate matter, photochemical oxidants, nitrogen dioxide and carbon monoxide, and lead. Short-term as well as long-term effects can be expected at levels exceeding WHO guidelines. The Latin American urban areas most affected by anthropogenic pollutant emissions are: the area of Sao Paulo (Brazil), the city of Santiago (Chile) and the metropolitan area of Mexico city. However, situations similar to those prevailing in these cities could well occur in other cities of latin America and the Caribbean. The population exposed to air-pollutant levels exceeding WHO guidelines can be estimated to 81 million or 26.5 percent of the total urban population of Latin America and 19 percent of its total population. These estimates correspond to 30 million children (0-14), 47 million adults (15-59) and 4 million elderly people (60+). To date a very limited number of epicemiological studies have been carried out to determine the potential health effects of air pollutants in Latin America. To obtain a rough estimate, a scenario was hypothesized in which subjects living in cities would be exposed to a given level of air pollutant, using data from the international literature to extrapolate the expected number of events in different strata of the hypothetical population. The estimated health effects are considerable and warrant priorty control intervention. This is true although epidemiological studies are needed to evaluate the health impact of specific pollutant compounds as well as their interactions in Latin American populations exposed to high levels of pollution. (AU)