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618 Genotoxic effects of anaesthetics
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Poster Session P31. Occupational toxicology
As the high temperatures of the production process can transform the amorphous silica in its different crystalline phases (from α-quartz to cristobalite), the study has carefully examined the composition of the raw materials by safety data sheet and the temperatures of the different production stages, this in order to address the investigation activitiy on the potentially highest-risk operations. Crystalline silica, as quartz or cristobalite, is classified as carcinogenic to humans since 1997 by IARC (group 1) with a TLV-TWA of 0.05 mg/m3 (ACGIH 2002) for respirable fraction. Data were collected following ACGIH curve (sampler: DorrOliver cyclone; flow rate: 1,7 l/m) and determination of SiO2 has been carried out by the means of XRD technique. Personal samplings were protracted for an average of 4–8 hours, in order to be representative of the whole working-day. In this preliminary investigation stage it has been observed that the mean personal exposure levels of respirable dust in the core-making area are equal to 1.5 mg/m3 (ACGIH2002), even as 95% upper confidential limits (2.2 mg/m3); anyway, in the 25% of samplings (relevant to workers of core-finishing and shell-moulding areas) the presence of crystalline silica was revealed as α-quartz, even if in concentrations lower than TLV-TWA (average = 0.039 mg/m3). 618
GENOTOXIC EFFECTS OF ANAESTHETICS
R. Rozgaj, V. Kašuba. Mutagenesis Unit, Institute for Medical Research and Occupational Health, Zagreb, Croatia Chronic occupational exposure to low concentrations of anaesthetic waste gases may entail adverse health effects. Genotoxicity tests may give information about the risk before it turns into a serious health hazard. It has been shown that anaesthetics cause DNA single-strand breaks in persons administering anaesthesia. Although DNA singlestrand breaks may be reversible, a part of them will not be repaired, which leads to irreversible damages. Some damages may be seen using cytogenetic methods. The purpose of this study was to evaluate the effects of exposure to anaesthetics (nitrous oxide and halothane) in a group of 28 operating room medical workers. To do that we used the single cell alkaline gel electrophoresis assay (comet assay) and cytochalasine b blocked micronucleus test (MN). The results were compared with those of 28 control subjects who were matched for sex, age and smoking habit. The statistical significance of the results was determined using the one-way ANOVA test. The results show a significant increase in the tail length (20.82) and tail moment (0.68) as well as in the micronuclei frequency (26.93‰) in exposed subjects with respect to controls (TL=16.16; TM=0.38; MN=11.89‰). The exposure duration was significantly associated with the frequency of micronuclei, while age was significant at the P<0.01 level in the tail length. Our results support the use of genotoxicity tests in monitoring occupational exposure to anaesthetics. 619
FUNCTIONAL IMPAIRMENT OF THE OLFACTORY SYSTEM IN HUMANS AFTER EXPERIMENTAL EXPOSURE TO 2-ETHYLHEXANOL
C. van Thriel, M. Schäper, E. Kiesswetter, M. Blaszkewicz, M. Kunze, A. Seeber. Leibniz Research Centre for Working Environment and Human Factors, University of Dortmund, Dortmund, Germany Unimpaired olfactory function is crucial for the identification of hazardous chemicals. Sustained solvent exposure impairs the olfactory function and a generalized impairment reducing the trigeminal sensitivity has been hypothesized. As a consequence early signs of sensory irritations (e.g., burning sensations) might be suppressed. Especially exposure peaks might have lasting effects on the chemosensory systems. In an exposure lab (≈29 cbm) two experiments with healthy male volunteers have been carried out. According to a cross-over design in experiment I (peaks) 24 subjects were exposed to 2ethylhexanol in three conditions with average concentrations of 1.5 ppm (constant), 10 ppm (hourly changing from 20 to 1.5 ppm), and 20 ppm (hourly changing from 40 to 1.5 ppm). In experiment II (constant) another group of 22 subjects was exposed to temporally constant concentrations of 1.5 ppm, 10 ppm, and 20 ppm. In both
experiments 4 subjects were exposed simultaneously for 4 h and a period of two exposure-free days between two successive trials was strictly adhered to. Before and after the three conditions of both experiments odor thresholds of 2-ethylhexanol were measured by means of an olfactometer. In experiment I the odor thresholds (OTs) increased in a dose-dependent manner. The concentration for reliable detection of 2-ethylhexanol increased across the three conditions from 0.06 to 0.17 ppm, 0.08 to 0.31 ppm, and 0.09 to 0.52 ppm, respectively. In experiment II the OTs were also affected by the exposures but no dose-dependency could be confirmed. The observed increases were 0.05 to 0.11 ppm, 0.06 to 0.22 ppm, and 0.06 to 0.21 ppm. Trigeminal sensitivity was not tested functionally. However, during high conditions (20 ppm) less sensation like burning and stinging were reported by those subjects showing the strongest threshold shifts. In conclusion, these results suggested that exposure peaks might amplify olfactory impairment and that interactions with the trigeminal sensitivity, crucial for regulatory toxicology, are possible. 620
OCCUPATIONAL EXPOSURE TO SEVOFLURANE AND MALE HEPATIC FUNCTION
G.F. Desogus. Study Reports of Toxicology, Azienda USL 7 di Carbonia, Italy The occupational exposure to anaesthetic causes changes in the biochemical markers and hepatic injury in exposed workers (surgeons, anesthesists, trained nurses). This work studies 1) the potential effect of sevoflurane exposure on the state of the hepatic markers (aspartate-aminotransferase and alanina-aminotransferase activity) 2) whether voluptary habits, including alcohol and smoke, can influence the haematic levels of sevoflurane. Sixty-eight sevoflurane exposed workers (group A: age 43 ± 8 years; years-old working seniority 11 ± 7 years) and twenty-one no exposed workers (group B: age 46 ± 3 years; years-old working seniority 16 ± 7 years) are examined in order to consider what is their hepatic function. The analysis of the hepatic markers don’t point out important differences between exposed and no exposed workers. The results of this study suggest that the sevoflurane doesn’t induce hepatoxicity in exposed workers of operating room. A reduced biodegradation and a quick elimination determine minimum effects at hepatocellular level in professionally exposed to sevoflurane workers. 621
THE RISK OF ALCOHOL ABUSE AND DEPENDENCE BESIDE OCCUPATIONAL STRESS IN A ISOLATED METALLURGY FACTORY
D. Ionescu 1 , E.A. Pauncu 2 , C. Cristescu 3 . 1 Department of Toxicology, University of Medicine and Pharmacie, “Victor Babes” of Timisoara, Timisoara, Roumanie, 2 Medicine of Work Department, University of Medicine and Pharmacie “Victor Babes” Timisoara, Timisoara, Roumanie, 3 Department of Pharmacology, University of Medicine and Pharmacie, Victor Babes" of Timisoara, Timisoara, Roumanie The main purpose of the present study was to investigate the relationship between occupational stress and risk for alcohol disorders. The research had the following stages: 1. At baseline, all of the 1714 workers in the company (66,51% male and 33,49% female) completed standardized interviews that measured socio-demographic and occupational variables and assessed whether had met diagnostic criteria for currently active alcohol abuse-dependence syndrome with a result of 439 (25,61%) positives persons. 2. It has been applied the Cage and Audit Test finding 115 (6,70%) alcohol-dependents persons. 3. Univariate analysis suggested that male gender, age (> 35– 40 years), lower socio-economics status, cigarette smoking, family history of alcohol addiction, jobs with high physical demands and low control, occupational injury, all was found to be significantly associated with the risk alcohol abuse. 4. Multivariate analysis showed that only family and personally addictive history and jobs with high physical and mental stressors demands was statistically significantly associated with increased risk of alcohol-dependence.
Poster Session P31. Occupational toxicology
As the high temperatures of the production process can transform the amorphous silica in its different crystalline phases (from α-quartz to cristobalite), the study has carefully examined the composition of the raw materials by safety data sheet and the temperatures of the different production stages, this in order to address the investigation activitiy on the potentially highest-risk operations. Crystalline silica, as quartz or cristobalite, is classified as carcinogenic to humans since 1997 by IARC (group 1) with a TLV-TWA of 0.05 mg/m3 (ACGIH 2002) for respirable fraction. Data were collected following ACGIH curve (sampler: DorrOliver cyclone; flow rate: 1,7 l/m) and determination of SiO2 has been carried out by the means of XRD technique. Personal samplings were protracted for an average of 4–8 hours, in order to be representative of the whole working-day. In this preliminary investigation stage it has been observed that the mean personal exposure levels of respirable dust in the core-making area are equal to 1.5 mg/m3 (ACGIH2002), even as 95% upper confidential limits (2.2 mg/m3); anyway, in the 25% of samplings (relevant to workers of core-finishing and shell-moulding areas) the presence of crystalline silica was revealed as α-quartz, even if in concentrations lower than TLV-TWA (average = 0.039 mg/m3). 618
GENOTOXIC EFFECTS OF ANAESTHETICS
R. Rozgaj, V. Kašuba. Mutagenesis Unit, Institute for Medical Research and Occupational Health, Zagreb, Croatia Chronic occupational exposure to low concentrations of anaesthetic waste gases may entail adverse health effects. Genotoxicity tests may give information about the risk before it turns into a serious health hazard. It has been shown that anaesthetics cause DNA single-strand breaks in persons administering anaesthesia. Although DNA singlestrand breaks may be reversible, a part of them will not be repaired, which leads to irreversible damages. Some damages may be seen using cytogenetic methods. The purpose of this study was to evaluate the effects of exposure to anaesthetics (nitrous oxide and halothane) in a group of 28 operating room medical workers. To do that we used the single cell alkaline gel electrophoresis assay (comet assay) and cytochalasine b blocked micronucleus test (MN). The results were compared with those of 28 control subjects who were matched for sex, age and smoking habit. The statistical significance of the results was determined using the one-way ANOVA test. The results show a significant increase in the tail length (20.82) and tail moment (0.68) as well as in the micronuclei frequency (26.93‰) in exposed subjects with respect to controls (TL=16.16; TM=0.38; MN=11.89‰). The exposure duration was significantly associated with the frequency of micronuclei, while age was significant at the P<0.01 level in the tail length. Our results support the use of genotoxicity tests in monitoring occupational exposure to anaesthetics. 619
FUNCTIONAL IMPAIRMENT OF THE OLFACTORY SYSTEM IN HUMANS AFTER EXPERIMENTAL EXPOSURE TO 2-ETHYLHEXANOL
C. van Thriel, M. Schäper, E. Kiesswetter, M. Blaszkewicz, M. Kunze, A. Seeber. Leibniz Research Centre for Working Environment and Human Factors, University of Dortmund, Dortmund, Germany Unimpaired olfactory function is crucial for the identification of hazardous chemicals. Sustained solvent exposure impairs the olfactory function and a generalized impairment reducing the trigeminal sensitivity has been hypothesized. As a consequence early signs of sensory irritations (e.g., burning sensations) might be suppressed. Especially exposure peaks might have lasting effects on the chemosensory systems. In an exposure lab (≈29 cbm) two experiments with healthy male volunteers have been carried out. According to a cross-over design in experiment I (peaks) 24 subjects were exposed to 2ethylhexanol in three conditions with average concentrations of 1.5 ppm (constant), 10 ppm (hourly changing from 20 to 1.5 ppm), and 20 ppm (hourly changing from 40 to 1.5 ppm). In experiment II (constant) another group of 22 subjects was exposed to temporally constant concentrations of 1.5 ppm, 10 ppm, and 20 ppm. In both
experiments 4 subjects were exposed simultaneously for 4 h and a period of two exposure-free days between two successive trials was strictly adhered to. Before and after the three conditions of both experiments odor thresholds of 2-ethylhexanol were measured by means of an olfactometer. In experiment I the odor thresholds (OTs) increased in a dose-dependent manner. The concentration for reliable detection of 2-ethylhexanol increased across the three conditions from 0.06 to 0.17 ppm, 0.08 to 0.31 ppm, and 0.09 to 0.52 ppm, respectively. In experiment II the OTs were also affected by the exposures but no dose-dependency could be confirmed. The observed increases were 0.05 to 0.11 ppm, 0.06 to 0.22 ppm, and 0.06 to 0.21 ppm. Trigeminal sensitivity was not tested functionally. However, during high conditions (20 ppm) less sensation like burning and stinging were reported by those subjects showing the strongest threshold shifts. In conclusion, these results suggested that exposure peaks might amplify olfactory impairment and that interactions with the trigeminal sensitivity, crucial for regulatory toxicology, are possible. 620
OCCUPATIONAL EXPOSURE TO SEVOFLURANE AND MALE HEPATIC FUNCTION
G.F. Desogus. Study Reports of Toxicology, Azienda USL 7 di Carbonia, Italy The occupational exposure to anaesthetic causes changes in the biochemical markers and hepatic injury in exposed workers (surgeons, anesthesists, trained nurses). This work studies 1) the potential effect of sevoflurane exposure on the state of the hepatic markers (aspartate-aminotransferase and alanina-aminotransferase activity) 2) whether voluptary habits, including alcohol and smoke, can influence the haematic levels of sevoflurane. Sixty-eight sevoflurane exposed workers (group A: age 43 ± 8 years; years-old working seniority 11 ± 7 years) and twenty-one no exposed workers (group B: age 46 ± 3 years; years-old working seniority 16 ± 7 years) are examined in order to consider what is their hepatic function. The analysis of the hepatic markers don’t point out important differences between exposed and no exposed workers. The results of this study suggest that the sevoflurane doesn’t induce hepatoxicity in exposed workers of operating room. A reduced biodegradation and a quick elimination determine minimum effects at hepatocellular level in professionally exposed to sevoflurane workers. 621
THE RISK OF ALCOHOL ABUSE AND DEPENDENCE BESIDE OCCUPATIONAL STRESS IN A ISOLATED METALLURGY FACTORY
D. Ionescu 1 , E.A. Pauncu 2 , C. Cristescu 3 . 1 Department of Toxicology, University of Medicine and Pharmacie, “Victor Babes” of Timisoara, Timisoara, Roumanie, 2 Medicine of Work Department, University of Medicine and Pharmacie “Victor Babes” Timisoara, Timisoara, Roumanie, 3 Department of Pharmacology, University of Medicine and Pharmacie, Victor Babes" of Timisoara, Timisoara, Roumanie The main purpose of the present study was to investigate the relationship between occupational stress and risk for alcohol disorders. The research had the following stages: 1. At baseline, all of the 1714 workers in the company (66,51% male and 33,49% female) completed standardized interviews that measured socio-demographic and occupational variables and assessed whether had met diagnostic criteria for currently active alcohol abuse-dependence syndrome with a result of 439 (25,61%) positives persons. 2. It has been applied the Cage and Audit Test finding 115 (6,70%) alcohol-dependents persons. 3. Univariate analysis suggested that male gender, age (> 35– 40 years), lower socio-economics status, cigarette smoking, family history of alcohol addiction, jobs with high physical demands and low control, occupational injury, all was found to be significantly associated with the risk alcohol abuse. 4. Multivariate analysis showed that only family and personally addictive history and jobs with high physical and mental stressors demands was statistically significantly associated with increased risk of alcohol-dependence.