Occult carbon monoxide poisoning in patients with neurologic illness

To investigate occult carbon monoxide poisoning in patients with neurologic illness, we prospectively studied 168 patients who presented to the emergency department between December 1987 and February 1988 with neurologic symptoms for evidence of carbon monoxide exposure. Patients with known carbon monoxide poisoning were excluded. The mean carboxyhemoglobin level was 3.1 percent; there were no significant differences in carboxyhemoglobin between categories of neurologic illness (F(5,162) = 1.35; p less than 0.25). Five patients (3 percent) had a carboxyhemoglobin greater than 10 percent, with levels ranging from 11.7 percent to 29.5 percent. After controlling for the effects of active and passive exposure to cigarette smoke, problems with the home heating system (odds ratio 9.6; p less than 0.03) and the presence of cohabitants with concurrent headache or dizziness (odds ratio 21.6; p less than 0.0001) were associated with an increased risk of a carboxyhemoglobin greater than 10 percent. A rule for obtaining carboxyhemoglobin tests only on patients who used gas stoves for heat or who had symptomatic cohabitants would have correctly identified all patients with carboxyhemoglobins greater than 10 percent, correctly excluded 77 percent of patients with lower levels, and eliminated the need for testing in 75 percent of cases. We conclude that unrecognized carbon monoxide poisoning occurs in a small but important fraction of patients with wintertime neurologic illness and can be identified by a characteristic risk factor profile.     

Passive and active exposure to cigarette smoke in a smoking experiment

Six volunteer female habitual smokers were exposed during a 2-wk experimental period to cigarette smoke, both actively and passively, in an exposure chamber (volume 10 m3, average air exchange rate 6.8 times/h), where the ambient carbon monoxide, particle, and aldehyde concentrations were monitored. Three of the six subjects were smoking at the time, 2 cigarettes (filtered, self-burning low tar brand) per person per hour, 30 cigarettes altogether during each of the 5-h experimental days in the chamber. Samples of blood and urine were taken from each subject after 3 nonsmoking days and after each day of active or passive smoking. Among the parameters tested, blood carboxyhemoglobin, plasma cotinine, and urinary mutagenicity were higher in samples taken after active smoking than after nonsmoking periods. Although the exposure conditions were similar for all subjects, the parameters measured showed quite high interindividual variation. Thioethers and thiocyanates were not significantly elevated in the active smoking samples; neither were there any differences during this short experimental period in the sister chromatid exchange frequencies. The only parameters showing an increasing trend after passive exposure, as compared with nonsmoking samples, were urinary mutagenicity and plasma cotinine, the main metabolite of nicotine.     

Analysis of sister chromatid exchange and micronuclei in peripheral blood lymphocytes of nurses handling cytostatic drugs.

The genotoxic effect of occupational exposure of 20 nurses who handled cytostatic drugs in medical oncology and haematology units was evaluated by micronucleus and sister chromatid exchange test. The duration of employment in the units and of exposure to cytostatics ranged from 1 to 31 years. The exposed nurses manifested an increase in cells with micronuclei as compared to the control group (P < 0.05). Nurses exposed to cytostatic drugs for 20-31 years showed a higher frequency of micronuclei (P < 0.05), whereas there was no difference in frequencies between the control group and the group exposed for 1-14 years (P > 0.05). The influence of the exposure period proved to be a significant parameter for the micronucleus test. No statistically significant differences were observed in sister chromatid exchange (P > 0.05).     

Toxicity of fire smoke

This review is an attempt to present and describe the major immediate toxic threats in fire situations. These are carbon monoxide, a multitude of irritating organic chemicals in the smoke, oxygen depletion, and heat. During the past 50 years, synthetic polymers have been introduced in buildings in very large quantities. Many contain nitrogen or halogens, resulting in the release of hydrogen cyanide and inorganic acids in fire smoke as additional toxic threats. An analysis of toxicological findings in fire and nonfire deaths and the results of animal exposures to smoke from a variety of burning materials indicate that carbon monoxide is still likely to be the major toxicant in modern fires. However, the additional toxic threats mentioned above can sometimes be the principal cause of death or their addition can result in much lower than expected carboxyhemoglobin levels in fire victims. This analysis also revealed that hydrogen cyanide is likely to be present in appreciable amounts in the blood of fire victims in modern fires. The mechanisms of action of acute carbon monoxide and hydrogen cyanide poisonings are reviewed, with cases presented to illustrate how each chemical can be a major contributor or how they may interact. Also, lethal levels of carboxyhemoglobin and cyanide in blood are suggested from an analysis of the results of a large number of fire victims from different fire scenarios. The contribution of oxygen depletion and heat stress are more difficult to establish. From the analysis of several fire scenarios, they may play a major role in the room of origin at the beginning of a fire. The results in animal studies indicate that when major oxygen depletion (<10%) is added to lethal or sublethal levels of carbon monoxide or hydrogen cyanide its major role is to substantially reduce the time to death. In these experiments the carboxyhemoglobin level at death was slightly reduced from the expected level with exposure to carbon monoxide alone. However, blood cyanide was reduced by a factor of ten from the expected level with exposure to hydrogen cyanide alone. This is another factor (among many other presented) complicating the task of establishing the contribution of cyanide in the death of fire victims, from its analysis in their blood. Finally the role of ethanol intoxication, as it may influence carboxyhemoglobin levels at death, is reviewed. Its role is minor, if any, but the data available on ethanol in brain tissue and blood of fire victims confirmed that brain ethanol level is an excellent predictor of blood ethanol.     

Toxicity of Fire Smoke

This review is an attempt to present and describe the major immediate toxic threats in fire situations. These are carbon monoxide, a multitude of irritating organic chemicals in the smoke, oxygen depletion, and heat. During the past 50 years, synthetic polymers have been introduced in buildings in very large quantities. Many contain nitrogen or halogens, resulting in the release of hydrogen cyanide and inorganic acids in fire smoke as additional toxic threats. An analysis of toxicological findings in fire and nonfire deaths and the results of animal exposures to smoke from a variety of burning materials indicate that carbon monoxide is still likely to be the major toxicant in modern fires. However, the additional toxic threats mentioned above can sometimes be the principal cause of death or their addition can result in much lower than expected carboxyhemoglobin levels in fire victims. This analysis also revealed that hydrogen cyanide is likely to be present in appreciable amounts in the blood of fire victims in modern fires. The mechanisms of action of acute carbon monoxide and hydrogen cyanide poisonings are reviewed, with cases presented to illustrate how each chemical can be a major contributor or how they may interact. Also, lethal levels of carboxyhemoglobin and cyanide in blood are suggested from an analysis of the results of a large number of fire victims from different fire scenarios. The contribution of oxygen depletion and heat stress are more difficult to establish. From the analysis of several fire scenarios, they may play a major role in the room of origin at the beginning of a fire. The results in animal studies indicate that when major oxygen depletion (<10%) is added to lethal or sublethal levels of carbon monoxide or hydrogen cyanide its major role is to substantially reduce the time to death. In these experiments the carboxyhemoglobin level at death was slightly reduced from the expected level with exposure to carbon monoxide alone. However, blood cyanide was reduced by a factor of ten from the expected level with exposure to hydrogen cyanide alone. This is another factor (among many other presented) complicating the task of establishing the contribution of cyanide in the death of fire victims, from its analysis in their blood. Finally the role of ethanol intoxication, as it may influence carboxyhemoglobin levels at death, is reviewed. Its role is minor, if any, but the data available on ethanol in brain tissue and blood of fire victims confirmed that brain ethanol level is an excellent predictor of blood ethanol.     

Evaluation of genotoxic risk of handling cytostatic drugs in clinical pharmacy practice

The genotoxic risk of handling antineoplastic drugs was evaluated in fifteen women preparing chemotherapeutics in the Pharmacy Department of the University Hospital Maastricht. Twenty nurses of the same hospital, who were not exposed to cytostatics, acted as controls. Endogenous exposure to antineoplastic drugs was assessed by determination of urine mutagenicity, as well as by analysis of urinary methotrexate levels. As genotoxicological end-points, sister chromatid exchanges and hypoxanthine guanine phosphoribosyl transferase locus point mutations were studied in peripheral lymphocytes obtained via venous puncture. No differences in urine mutagenic activity, in sister chromatid exchange frequencies and in hypoxanthine guanine phosphoribosyl transferase point mutation frequencies between exposed and non-exposed groups were detected. Higher sister chromatid exchange frequency was observed in smokers as compared to non-smokers.     

A case of carbon monoxide poisoning with thrombus in the heart: a case report

Carbon monoxide is a nonirritant, odorless, colorless gas, and is lighter than air. It is an end product of the incomplete combustion of hydrocarbons. Its effects are most prominent in organs sensitive to oxygen deprivation, such as the heart, brain, and kidney. Carbon monoxide poisoning becomes more abundant in winter and at cold places. In Turkey, every year we see several deaths due to poisonous gas leaks from coal or wood stoves. Deaths particularly due to hypoxia-related central nervous system damage and ventricular dysrhythmias are observed. On the other hand, an association between thromboembolic accidents and carbon monoxide poisoning has been shown in literature. Thromboembolic accidents in the mesenteric, central nervous system, and extremities are reported. However, no atrial thrombus has been mentioned. In this study, a case of an atrial thrombus associated with carbon monoxide poisoning following a diagnosis of carbon monoxide poisoning and treatment in the emergency room is reported and the literature is revisited.     

A Case of Carbon Monoxide Poisoning with Thrombus in the Heart: A Case Report

Carbon monoxide is a nonirritant, odorless, colorless gas, and is lighter than air. It is an end product of the incomplete combustion of hydrocarbons. Its effects are most prominent in organs sensitive to oxygen deprivation, such as the heart, brain, and kidney. Carbon monoxide poisoning becomes more abundant in winter and at cold places. In Turkey, every year we see several deaths due to poisonous gas leaks from coal or wood stoves. Deaths particularly due to hypoxia-related central nervous system damage and ventricular dysrhythmias are observed. On the other hand, an association between thromboembolic accidents and carbon monoxide poisoning has been shown in literature. Thromboembolic accidents in the mesenteric, central nervous system, and extremities are reported. However, no atrial thrombus has been mentioned. In this study, a case of an atrial thrombus associated with carbon monoxide poisoning following a diagnosis of carbon monoxide poisoning and treatment in the emergency room is reported and the literature is revisited.     

Chromosome damage in workers in cigarette manufacturing industry

To investigate whether occupational exposure to tobacco dust is genotoxic, a group of employees in a tobacco factory was tested for structural chromosome aberrations (CA), cytokinesis-block micronucleus assay (CBMN) and sister chromatid exchanges (SCE) that are well established as indicators of early biological effects. The study group consisted of 40 tobacco workers and an equal number of matched controls. The results obtained in the exposed group showed a significant increase in chromosome aberrations (R=0.26), micronucleus frequency (R=0.56) and in sister chromatid exchanges (R=0.75), which was additionally influenced by smoking. A significant increase in high frequency cells (HFC) in the exposed group was also observed. Like the SCE frequency, the HFC frequency increased significantly in smokers of the control and exposed smokers. The study indicates that occupational exposure to tobacco dust induces genome damage. A higher risk was observed in women. The micronucleus frequency and sister chromatid exchange tests seem to be more reliable indicators of genome damage than chromosome aberrations in monitoring chronically exposed subjects.     

Impaired mitochondrial respiration and protein nitration in the rat hippocampus after acute inhalation of combustion smoke

Survivors of massive inhalation of combustion smoke endure critical injuries, including lasting neurological complications. We have previously reported that acute inhalation of combustion smoke disrupts the nitric oxide homeostasis in the rat brain. In this study, we extend our findings and report that a 30-minute exposure of awake rats to ambient wood combustion smoke induces protein nitration in the rat hippocampus and that mitochondrial proteins are a sensitive nitration target in this setting. Mitochondria are central to energy metabolism and cellular signaling and are critical to proper cell function. Here, analyses of the mitochondrial proteome showed elevated protein nitration in the course of a 24-hour recovery following exposure to smoke. Mass spectrometry identification of several significantly nitrated mitochondrial proteins revealed diverse functions and involvement in central aspects of mitochondrial physiology. The nitrated proteins include the ubiquitous mitochondrial creatine kinase, F1-ATP synthase α subunit, dihydrolipoamide dehydrogenase (E3), succinate dehydrogenase Fp subunit, and voltage-dependent anion channel (VDAC1) protein. Furthermore, acute exposure to combustion smoke significantly compromised the respiratory capacity of hippocampal mitochondria. Importantly, elevated protein nitration and reduced mitochondrial respiration in the hippocampus persisted beyond the time required for restoration of normal oxygen and carboxyhemoglobin blood levels after the cessation of exposure to smoke. Thus, the time frame for intensification of the various smoke-induced effects differs between blood and brain tissues. Taken together, our findings suggest that nitration of essential mitochondrial proteins may contribute to the reduction in mitochondrial respiratory capacity and underlie, in part, the brain pathophysiology after acute inhalation of combustion smoke.     

Health effects of subchronic exposure to low levels of wood smoke in rats.

Wood smoke is a significant source of air pollution in many parts of the United States, and epidemiological data suggest a causal relationship between elevated wood smoke levels and health effects. The present study was designed to provide information on the potential respiratory health responses to subchronic wood smoke exposures in a Native American community in New Mexico. Therefore, this study used the same type of wood under similar burning conditions and wood smoke particle concentrations to mimic the conditions observed in this community. Brown Norway rats were exposed 3 h/day, 5 days/week for 4 or 12 weeks to air as control, or to 1 or 10 mg/m3 concentrations of wood smoke particles from pinus edulis. The wood smoke consisted of fine particles (< 1 microm) that formed larger chains and aggregates having a size distribution of 63-74% in the < 1-microm fraction and 26-37% in the > 1-microm fraction. The particle-bound material was primarily composed of carbon, and the majority of identified organic compounds consisted of sugar and lignin derivatives. Pulmonary function, specifically carbon monoxide-diffusing capacity and pulmonary resistance, was somewhat affected in the high-exposure group. Mild chronic inflammation and squamous metaplasia were observed in the larynx of the exposed groups. The severity of alveolar macrophage hyperplasia and pigmentation increased with smoke concentration and length of exposure, and the alveolar septae were slightly thickened. The content of mucous cells lining the airways changed from Periodic Acid Schiff- to Alcian Blue-positive material in the low-exposure group after 90 days. Together, these observations suggest that exposure to wood smoke caused minor but significant changes in Brown Norway rats. Further studies are needed to establish whether exposure to wood smoke exacerbates asthmalike symptoms that resemble those described for children living in homes using wood stoves for heating and cooking.     

Analysis of sister chromatid exchange, micronucleus and chromosomal aberration frequencies in rodents exposed to mosquito coil smoke by inhalation route

Mosquito coil smoke emitting from a mosquito repellent, was tested for its mutagenic effect in bone marrow cells from mouse and rat after 4 h acute inhalation exposure. Coil smoke with suspended particulate concentrations of 99–129 mg/m³, significantly elevated the frequencies of sister chromatid exchanges in bone marrow cells and micronuclei in polychromatic erythrocytes. Analysis of chromosomal aberrations in metaphases also revealed a significantly higher incidence of chromosomal aberration frequency in exposed rats and mice.     

Genotoxicity of thimerosal in cultured human lymphocytes with and without metabolic activation sister chromatid exchange analysis proliferation index and mitotic index

Thimerosal is an antiseptic containing 49.5% of ethyl mercury that has been used for years as a preservative in many infant vaccines and in flu vaccines. Thimerosal is an organic mercurial compound used as a preservative in biomedical preparations. In this study, we evaluated the genotoxic effect of thimerosal in cultured human peripheral blood lymphocytes using sister chromatid exchange analysis in culture conditions with and without S9 metabolic activation. This study is the first report investigating the genotoxic effects of thimerosal in cultured human peripheral blood lymphocyte cells using sister chromatid exchange analysis. An analysis of variance test (ANOVA) was performed to evaluate the results. Significant induction of sister chromatid exchanges was seen at concentrations between 0.2 and 0.6 μg/ml of thimerosal compared with negative control. A significant decrease (p < 0.001) in mitotic index (MI) and proliferation ındex (PRI) as well as an increase in SCE frequency (p < 0.001) was observed compared with control cultures. Our results indicate the genotoxic and cytotoxic effect of TH in cultured human peripheral blood lymphocytes at tested doses in cultures with/without S9 fraction.     

Genotoxicity studies of the food additive ester gum.

Ester gum (EG) is used in citrus oil-based beverage flavourings as a weighting or colouring agent. In the present study, concentrations of 50, 100 and 150 mg/kg body weight were administered orally to male Swiss albino mice, and sister chromatid exchange and chromosomal aberration were used as the cytogenetic endpoints to determine the genotoxic and clastogenic potential of the food additive. Although EG was weakly clastogenic and could induce a marginal increase in sister chromatid exchange frequencies, it was not a potential health hazard at the doses tested.     

The content of carbon monoxide in the tissues of rats intoxicated with carbon monoxide in various conditions of acute exposure

Tissue carbon monoxide (CO) content was investigated in rats severely intoxicated with CO under various exposure conditions: 1% CO for 4 min, 0.4% CO for 40 min and 0.12% CO for 12 h. Extravascular CO was determined in the heart and skeletal muscles immediately after termination of exposure, and carboxymyoglobin (MbCO) percent saturation was calculated. Total brain CO was estimated immediately after termination of exposure and after the time periods of restitution.After the same exposure conditions, MbCO percent saturation was higher in the heart than in skeletal muscle. In both types of muscle, saturation of myoglobin (Mb) with CO depended on blood carboxyhemoglobin (HbCO) level and not on the duration of exposure. The time course of CO elimination was the same for blood and brain, irrespective of CO exposure conditions.The results obtained showed that acute CO intoxication induced by long duration exposures did not involve CO accumulation in the tissues.     

Evaluation of current derivative spectrophotometric methodology for the determination of percent carboxyhemoglobin saturation in postmortem blood samples

Carbon monoxide intoxication continues to be a commonly encountered cause of death in most areas of Canada. The forensic nature of the samples in these cases presents special problems that are not normally encountered in clinical determinations. A study was undertaken to assess various methods of determining the percent carboxyhemoglobin saturation in blood, more specifically, those using derivative spectrophotometric measurements in the Soret region of the UV spectrum. At the same time, other studies were carried out: the effects of storage time on the carboxyhemoglobin levels; evaluation of sample containers; comparison of percent carboxyhemoglobin saturation in blood samples taken ante-mortem and post-mortem. Blood for the study was obtained from laboratory animals that were exposed to carbon monoxide before death.     

Studies on the genotoxicity of the anabolic drugs trenbolone and zeranol

The androgen trenbolone, and the mycoestrogen zeranol, both anabolic drugs, were tested for their genotoxic potential. Test systems were the SOS-chromotest, the rec-assay and the V79 sister chromatid exchange test without and with metabolic activation using rat liver homogenates and primary rat hepatocytes.It is still a matter of debate if trenbolone has carcinogenic properties, because of its cell transforming activity in vitro. Trenbolone, however, did not demonstrate any genotoxic effect in the assays performed. The results obtained for zeranol were also negative in the SOS-chromotest and V79 sister chromatid exchange test but positive in the rec-assay.     

Genotoxic potential of acephate technical: in vitro and in vivo effects

The genotoxic potential of acephate technical (AT) in vitro and in vivo has been studied in bioassays detecting primary DNA damage, chromosomal alterations, and gene mutation. Results from in vitro assays have ranged from negative to weakly positive; AT is apparently a direct-acting agent in these tests. However, expressed in terms of molar potency, AT has generally been at least 100-1000 times less potent than known positive mutagens tested in vitro. Following in vivo exposure at maximum tolerated doses, AT did not induce chromosomal aberrations, sister chromatid exchange, or micronuclei in mouse bone marrow cells; a dominant lethal study in mice was also negative. In a supplemental study, no induced chromosomal aberrations or sister chromatid exchange could be detected in lymphocytes from a pair of cynomolgus monkeys following exposure to AT at a low dose level for 20 days. At dose levels limited by toxicity, no positive results were observed for induction of sex-linked, recessive lethality in D. melanogaster. Acephate technical (ORTHENE) appears to present little or no genetic hazard to in vivo mammalian systems.     

Application of end-exhaled breath monitoring to assess carbon monoxide exposures of wildland firefighters at prescribed burns

Exposure to the range of combustion products from wildland fires has been demonstrated to cause respiratory irritation and decreased lung function among firefighters. The measurement of carbon monoxide (CO) has been previously shown to be highly correlated with the range of contaminants found in wildland fires. In this article, we assess the feasibility of using a simple, noninvasive biological test to assess exposure to CO for a group of wildland firefighters. Measurements of CO exposure were collected using personal monitors as well as in exhaled breath for wildland firefighters who conducted prescribed burns in February-March 2004. Overall, the CO concentrations measured in this study group were low with a shift mean of 1.87 ppm. Correspondingly, the cross-shift difference in carboxyhemoglobin as estimated from exhaled breath CO levels was also low (median increase =+0.2% carboxyhemoglobin). The use of exhaled breath measurements for CO has limitations in characterizing exposures within this worker population.     

Wood stove effects on indoor air quality in Brazilian homes: carcinogens, suspended particulate matter, and nitrogen dioxide analysis.

The effects of wood burning stoves on indoor air quality was investigated in a rural community of southern Brazil, during the winter season of 1991. The concentrations of polycyclic aromatic hydrocarbons (PAHs), nitrogen dioxide (NO2) and suspended particulate matter (SPM) were assessed in houses with wood stoves and the results compared with levels found in houses with gas stoves. Strikingly higher (p < 0.01) levels of PAHs, and much higher (p = 0.07) levels of SPM were found in the kitchens with wood stoves. In contrast, NO2 concentrations in the kitchen as well in personal exposure, were found to be slightly higher in houses with gas stoves. All these differences were minimally affected by smoking, outdoor air pollution or other emissions from indoor combustion products. These findings appear to support the hypothesis that domestic wood burning stoves are risk factors for some upper digestive and respiratory tract cancers in Brazil.