Disulfiram as an Indicator of Human Susceptibility to Carbon Disulfide

It may be assumed that carbon disulfide and disulfiram (Antabuse) are metabolized by the same or similar enzyme system. By determination of diethyldithiocarbamates (DDC) in the urine after disulfìram administration it is hoped to evaluate the rate of which sulfur compounds are metabolized in various groups of workers exposed to CS₂ in the viscose factory.

It seems that the increase in CS₂ exposore causes a decrease in the DDC excretion with the lowest value in once-poisoned workers.

It is supposed that differences between controls and poisoned workers are showing the capacity of individuals to metabolize the sulfur compounds. It is hoped that such tests will provide an index of metabolism to assure suitable job placement by detecting those workers who will not be hypersus- ceptible to the effects of CS₂.     

IODINE-AZIDE TEST ON URINE OF PERSONS EXPOSED TO CARBON DISULPHIDE

The iodine-azide test was performed on the urine of workers exposed to carbon disulphide in a viscose factory. The exposure coefficient was determined before, during, and after the working time, and showed a good correlation with the exposure.

Workers exposed to a high concentration of carbon disulphide could be divided in two groups. The first group showed normal values of the exposure coefficient before work but low values at the end. (The coefficient is inversely related to the exposure.) In the second group, the workers started work with slightly decreased values and ended with greatly decreased ones.

We are pursuing this study to establish why recovery in the second group was not complete.

     

Accumulation of carbon disulphide metabolites

Summary Biological monitoring for carbon disulphide (CS₂) exposure performed using the iodine-azide test (IAT) and 2-thiothiazolidine-4-carboxylic acid (TTCA) test in urinalysis of workers with high exposure to CS₂ (112–142 mg/m³, n = 34), workers with low exposure (4–7 mg/m³, n = 16), and non-exposed university workers (n =10). Pre-shift and post-shift urine specimens were collected on three consecutive days in the exposed and for only one day in the non-exposed. According to the findings the specificity and the sensitivity seem to be low for the IAT and high for the TTCA test. Contrary to a previous report all pre-shift urine samples showed negative IATs. The TTCA test was positive in pre-shift urine even after 32 to 63.5 h without exposure, and values tended to increase during consecutive days of exposure in highly exposed workers.The possible health implications of these findings should be further investigated.     

Relevancy of bivalent sulphur excretion to carbon disulphide exposure in different metabolic conditions

Magos, L. (1972).Brit. J. industr. Med.,29, 90-94. Relevancy of bivalent sulphur excretion to carbon disulphide exposure in different metabolic conditions. A quantitative spectrophotometric method for the estimation of urinary bivalent sulphur by its catalytic effect on the iodine-azide reaction has been developed for rats exposed to carbon disulphide (CS₂). Urinary CS₂ was also determined. Exposure to CS₂ increased the excretion of bivalent sulphur in both fed and starved animals, but the increase in starved animals was significantly less than in fed animals. Starvation also decreased the urinary excretion of CS₂. Phenobarbitone pretreatment, which induced liver damage in animals subsequently exposed to CS₂, had no effect on either bivalent sulphur or CS₂ excretion. Three dithiocarbamate fungicides, Thiram, Ziram, and Zineb, given by mouth increased the excretion of bivalent sulphur in the following order: Zineb<Ziram<Thiram.

After 250 mg/kg sodium diethyldithiocarbamate (DDC) given intraperitoneally the same amount of CS₂ was excreted in the urine as after 4 hours' exposure to 2·0 mg/l CS₂, but the bivalent sulphur excretion was six times higher. Starvation did not decrease the excretion of CS₂ or bivalent sulphur after DDC.

     

Laboratory Results of Some Biological Measures in Workers Exposed to Lead

Erythrocyte ALA-dehydratase (ALAD) activity and blood lead levels were studied in different groups of subjects not occupationally exposed to lead, ie, male and female clerical workers, traffic policemen, motorway tollgate attendants, and chronic alcoholics in comparison with values obtained in workers in a lead- using industry.

Among the subjects without occupational exposure to lead, the highest mean values of erythrocyte ALAD activity and the lowest mean values of lead in the blood were found in female clerical workers. Progressively lower mean values of ALAD activity and conversely higher mean values of lead in the blood were observed in the male clerical workers, traffic policemen, motorway tollgate attendants, and chronic alcoholics.

In workers occupationally, exposed to lead, erythrocyte ALAD activity undergoes much greater reductions not only in the manifest phases of lead poisoning but even at the very beginning of exposure, and ALAD remains reduced even some time after exposure has ceased.     

Biological monitoring of workers exposed to carbon disulfide (CS2) in a viscose rayon fibers factory

The exposure-excretion relationship to carbon disulfide (CS₂) vapor in 407 exposed workers was studied during the second half of the working week. Carbon disulfide concentrations were also determined in 50 nonexposed subjects. The geometric mean value for CS₂ in urine samples from the latter was: 0.23 μg/l (95% upper limit = 0.52 μg/l) when log-normal distribution was assumed. Among the exposed workers, the CS₂ level in urine samples collected after the first half shift exceeded the 95% upper limit of nonexposed subjects in every case. The time-weighted average intensity of exposure to CS₂ vapor was measured using personal diffusive samplers (in which carbon cloth served as an adsorbent). CS₂ concentrations in urine were determined in samples collected at the end of the first half shift from the 407 exposed cases as well as from 50 nonexposed controls. There was a significant correlation (p < 0.0001) between the exposure to CS₂ vapor at concentrations of up to 64 mg/m³ and the levels of CS₂ measured in the urine samples after four hours of exposure. The correlation indicated that a mean level of 15.5 μg CS₂/l urine (95% confidence range, 13.8–17.1 μg/l) was excreted following an exposure to CS₂ at 31 mg/m³ (the current occupational exposure limit). Am. J. Ind. Med. 33:478–484, 1998. © 1998 Wiley-Liss, Inc.     

Modeling of occupational exposure to accidentally released manufactured nanomaterials in a production facility and calculation of internal doses by inhalation

Background: Occupational exposure to manufactured nanomaterials (MNMs) and its potential health impacts are of scientific and practical interest, as previous epidemiological studies associate exposure to nanoparticles with health effects, including increased morbidity of the respiratory and the circulatory system.

Objectives: To estimate the occupational exposure and effective internal doses in a real production facility of TiO₂ MNMs during hypothetical scenarios of accidental release.

Methods: Commercial software for geometry and mesh generation, as well as fluid flow and particle dispersion calculation, were used to estimate occupational exposure to MNMs. The results were introduced to in-house software to calculate internal doses in the human respiratory tract by inhalation.

Results: Depending on the accidental scenario, different areas of the production facility were affected by the released MNMs, with a higher dose exposure among individuals closer to the particles source.

Conclusions: Granted that the study of the accidental release of particles can only be performed by chance, this numerical approach provides valuable information regarding occupational exposure and contributes to better protection of personnel. The methodology can be used to identify occupational settings where the exposure to MNMs would be high during accidents, providing insight to health and safety officials.     

Effect of Tetraethyl Thiuram Disulphide (Disulfiram) on Metabolism of Trichloroethylene in Man

The amounts of trichloroethanol and trichloroacetic acid excreted in the urine of four subjects who inhaled trichloroethylene in a concentration of about 1 mg./l. for a period of five hours in a laboratory experiment were determined. This experiment was repeated under the same conditions after tetraethyl thiuram disulphide (disulfiram) had been given in divided doses, totalling 3 or 3·5 g. The elimination of trichloroethanol in urine was decreased by 40 to 64%, and of trichloroacetic acid by 72 to 87%. The trichloroethylene excreted by the lungs in two of the subjects increased up to 65% of that retained within five hours. It is concluded that tetraethyl thiuram disulphide (disulfiram) strikingly inhibits the oxidation of trichloroethylene.

The possible therapeutic use of this substance in cases of severe peroral trichloroethylene intoxication is discussed.

     

An Epidemiologic Study of the Effects of Carbon Disulfide on the Peripheral Nerves

Abstract

Although the labor inspection had disclosed considerable exposure to carbon disulfide (CS₂) in a Belgian viscose rayon factory, the company medical officer had not diagnosed any case of polyneuropathy in association with CS₂ exposure, although this finding had been extensively reported in the literature. Personal monitoring of CS₂ exposure was performed in 17 jobs. Because the working conditions in the factory had not changed since 1932, a CS₂ cumulaiive exposure index (CS₂ index) could be calculated for each individual. Examination of the exposed subjects (n = 111) included a self-administered questionnaire, a clinical neurologic examinaiion, and electroneuromyography. Seventy-four workers from other plants, not exposed to CS₂ or to any other neurotoxcc agent, served as referents. The average CS2 exposures of the study group ranged from 4 to 112 mg/m³. The data were analyzed with multiple regression method, adjusting the effect of exposure for a number of possible confounders. Significant associations were found between the cumulative CS₂ index and symptoms consistent with polyneuropathy in the legs and with abnormal recruitment pattern and decrease of motor conduciion velocities of the peroneal nerves. Exposures to CS₂ at levels below the present threshold limit value (31 mg/m³) were associated with significant decreases of motor conduciion velocity.     

Urinary levoglucosan as a biomarker for woodsmoke exposure in wildland firefighters

Abstract

Background: Levoglucosan, a sugar anhydride and a combustion breakdown product of cellulose is a dominant organic constituent of particles in woodsmoke. After exposure, levoglucosan is excreted unmetabolized in urine.

Objective: Urinary levoglucosan was assessed as a biomarker of occupational woodsmoke exposure among wildland firefighters.

Methods: Urine samples were collected from wildland firefighters before and after their work-shifts on days when they worked at prescribed burns. A total of 97 pairs of pre- and post-shift urine samples were collected from 19 firefighters over 10 prescribed burn shifts. The urine samples were analyzed to determine whether there was an increase in the concentration of levoglucosan from pre- to post-shift after the firefighters had worked at the prescribed burns.

Results: Overall, there was an increase in both the urinary volume-based and creatinine corrected levoglucosan concentrations from pre- to post-shift (P<0·05). However, the direction of change in the concentrations was not consistent. There were increases in urinary levoglucosan concentration from pre- to post-shift in 63% of the person-day samples, and in only 58% of the person-day samples for the creatinine corrected concentrations.

Conclusion: Although there was an overall increase in urinary concentrations of levoglucosan, results suggest that other sources apart from woodsmoke affected the urinary levels of this biomarker in wildland firefighters. Therefore, urinary levoglucosan may not be effective as a biomarker of woodsmoke exposure in this setting.     

American Ginseng Supplementation Induces an Oxidative Stress in Postmenopausal Women

Objective: To determine whether American ginseng (Panax Quinquefolium) confers antioxidant protection to postmenopausal women at rest and after a mild aerobic exercise session.

Methods: In this double-blinded parallel study, 12 female subjects (age range 55–75) consumed two capsules, containing 500 mg of dry American ginseng whole-root powder, everyday for 4 months, whereas 13 female control subjects of the same age range consumed two placebo capsules. Before and after the supplementation regimen each subject performed 30 minutes of treadmill walking on a 5% grade incline at an estimated 60% of VO₂max.

Results: Ginseng supplementation had no effect on heart rate, blood pressure, plasma blood glucose, or lactate concentration at rest or immediately after exercise tests. The ginseng supplemented group displayed a higher resting plasma glutathione disulfide (GSSG) concentration and lower glutathione (GSH):GSSG ratio, as well as a lower resting total antioxidant content (TAC). Plasma GSSG concentration decreased, whereas the GSH:GSSG ratio and TAC increased after exercise in all subjects. Furthermore, plasma malondialdehyde and urine 8-hydroxydeoxyguanosine concentrations were elevated in the ginseng-supplemented group. Erythrocyte superoxide dismutase and GSH reductase activities were increased after ginseng supplementation. The 30-minute treadmill walking, however, did not alter these changes.

Conclusions: These data suggest that chronic American ginseng supplementation at the given dose can cause an oxidative stress in postmenopausal women, as reflected by the elevated oxidative damage markers and the increased erythrocyte antioxidant enzyme activity.     

Monitoring of occupational exposure to dichloromethane by diffusive vapor sampling and urinalysis

Objective: The aim of the present study was to develop valid methods for monitoring of occupational exposure to dichloromethane (DCM). Methods: Carbon cloth as an adsorbent in diffusive sampling was tested for its capacity to adsorb DCM vapor and to retain adsorbed DCM after termination of the exposure. Urine samples collected from DCM-exposed workers were analyzed for DCM by the head-space technique. After extraction with carbon disulfide, DCM in the cloth was analyzed on a DB-WAX capillary column by flame-ionization detection gas chromatography (FID-GC) and DCM in urine was analyzed by electron-capture detection (ECD)-GC. Results: The diffusive sampling with carbon cloth as an adsorbent is applicable to 4-h monitoring of exposure to up to 100 ppm DCM vapor. DCM concentrations detected in end-of-shift urine samples correlated linearly with time-weighted average DCM concentrations measured in the breathing-zone␣air␣of the exposed workers; essentially the same exposure-excretion relationship was obtained by vapor monitoring for the afternoon 4-h period as compared with a whole day (8-h) of vapor monitoring. There was no sex difference in the exposure-excretion relation. Conclusions: Both personal diffusive sampling (at up to 100 ppm DCM and for up to 4 h) and biological exposure monitoring by urinalysis for DCM are applicable in occupational health as reliable measures of exposure to this chlorinated hydrocarbon solvent. Received: 22 October 1997 / Accepted: 26 February 1998     

Interrelationships between lead in blood, lead in urine, and ALA in urine during lead work

Selander, S., and Cramér, K. (1970).Brit. J. industr. Med.,27, 28-39. Interrelationships between lead in blood, lead in urine and ALA in urine during lead work. One hundred and seventy-seven workers from a storage battery factory were examined for lead in blood and lead and δ-aminolevulinic acid (ALA) in urine. The workers were selected at random from those who had been employed for more than one month;most had been employed for several years at the same job. Thirty-six workers were from departments with no lead exposure. In three departments with high exposure a rotating system with three weeks' exposure and three weeks' non-exposed work was applied. As the aim of the study was to establish the relationships between the three parameters during constant exposure, the values from these men were treated separately.

The relationship between lead in blood and urinary ALA was best described by a curvilineat function: ALA = 10^0·0157 Pb_b-^1·0985, while the regression lines for ALA on lead in urine, and lead in urine on lead in blood were straight.

Workers from the departments with the rotating system showed lower values for urinary lead and ALA, compared with non-rotating workers with the same level of lead in blood. All these workers were examined during their second or third week of lead work, i.e., with an accumulating lead body burden. This system may be beneficial, especially in departments where prophylactic measures are difficult to install, or for notoriously careless workers.

Those who showed comparatively high ALA and urinary lead values in relation to their blood lead level were found to be workers with repeated incidents of metabolic lead influence, in whom the ALA values had seldom been normal.

The mean values from different factory departments were of the same order as would be expected from previous studies in storage battery plants.

The results are discussed in relation to present concepts of lead absorption and poisoning.

     

Effect of environmental exposure to hydrogen sulfide on central nervous system and respiratory function: a systematic review of human studies

Background: Assessment of the health effects of low-level exposure to hydrogen sulfide (H₂S) on humans through experiments, industrial, and community studies has shown inconsistent results.

Objective: To critically appraise available studies investigating the effect of H₂S on the central nervous system (CNS) and on respiratory function.

Methods: A search was conducted in 16 databases for articles published between January 1980 and July 2014. Two researchers independently evaluated potentially relevant papers based on a set of inclusion/exclusion criteria.

Results: Twenty-seven articles met the inclusion criteria: 6 experimental, 12 industry-based studies, and 10 community-based studies (one article included both experimental and industry-based studies). The results of the systematic review varied by study setting and quality. Several community-based studies reported associations between day-to-day variations in H₂S levels and health outcomes among patients with chronic respiratory conditions. However, evidence from the largest and better-designed community-based studies did not support that chronic, ambient H₂S exposure has health effects on the CNS or respiratory function. Results from industry-based studies varied, reflecting the diversity of settings and the broad range of H₂S exposures. Most studies did not have individual measurements of H₂S exposure.

Discussion: The results across studies were inconsistent, justifying the need for further research.     

Nitrogen dioxide and acute respiratory tract infections in children in Indonesia

Abstract

We evaluated associations between air pollution (nitrogen dioxide [NO₂] and sulfur dioxide [SO₂]) and health in children aged 0–3?years in Indonesia. We included 4931 Indonesian children born between 2009 and 2011. We assigned participants provincial-levels of NO₂ and SO₂ and examined associations with low birth weight, infant death, neonatal death, and acute respiratory infection (ARI). We estimated odds ratios (OR) and 95% confidence intervals (CI) using a generalized estimating equations logistic regression model. NO₂ exposure increased the risk for ARI. An interquartile range increase in mean NO₂ exposure increased the risk for ARI by 18% (OR 1.18, 95% CI: 1.08–1.28), and was supported by quartile exposure category. SO₂ was not associated with the examined child health outcomes. NO₂ exposure increased the risk for respiratory infections in early childhood in Indonesia. Abbreviations ARI acute respiratory infection

CI confidence interval

GDRB Gross Domestic Regional Bruto

GEE generalized estimating equations

IDHS Indonesian Demographic Health Survey

IQR interquartile range

LBW low birth weight

NO₂ nitrogen dioxide

OR odds ratio

SO₂ sulfur dioxide

     

Metal dust exposure and lung function deterioration among steel workers: an exposure-response relationship

Background: Metallic dust is a heterogeneous substance with respiratory sensitizing properties. Its long term exposure adversely affected lung function, thus may cause acute or chronic respiratory diseases.

Methods: A cross-sectional study was conducted in a steel factory in Terengganu, Malaysia to assess the metal dust exposure and its relationship to lung function values among 184 workers. Metal dust concentrations values (Co, Cr, and Ni) for each worker were collected using air personal sampling. Lung function values (FEV₁, FVC, and %FEV₁/FVC) were determined using spirometer.

Results: Exposure to cobalt and chromium were 1–3 times higher than permissible exposure limit (PEL) while nickel was not exceeding the PEL. Cumulative of chromium was the predictor to all lung function values (FEV₁, FVC, and %FEV₁/FVC). Frequency of using mask was positively associated with FVC (Adj b = 0.263, P = 0.011) while past respiratory illnesses were negatively associated with %FEV₁/FVC (Adj b = –1.452, P = 0.026). Only few workers (36.4%) were found to wear their masks all times during the working hours.

Conclusions: There was an exposure-response relationship of cumulative metal dust exposure with the deterioration of lung function values. Improvement of control measures as well as proper and efficient use or personal protection equipment while at work could help to protect the respiratory health of workers.     

Long-term γ-hydroxybutyric acid (GHB) and disulfiram combination therapy in GHB treatment-resistant chronic alcoholics

Leading Italian studies support the use of γ-hydroxybutyric acid (GHB), not only in the treatment of the alcohol withdrawal syndrome, but also in maintaining alcohol abstinence. GHB gives a better result than naltrexone and disulfiram in maintaining abstinence, and it has a better effect on craving than placebo or disulfiram. The problem is that about 30-40% of alcoholics are non-responders to GHB therapy. In our clinical practice, we speculate that by combining disulfiram with GHB treatment we may be able to achieve a kind of 'antagonist' effect by using the 'psychological threat' of disulfiram (adversative effect) while taking advantage of the anticraving effect of GHB, despite the limitation of its 'non-blockade' effect on alcohol. In this context, to improve the outcome in GHB long-term treated alcoholics, we added disulfiram to GHB in the management of GHB treatment-resistant alcoholics. In this study we compared retention in treatment of 52 patients who were treated with the GHB-disulfiram combination for up to six months, with retention for the same subjects considering their most recent unsuccessful outpatient long-term treatment with GHB only. An additional comparison was carried out on the days of complete abstention from alcohol. Thirty four patients (65.4%) successfully completed the protocol and were considered to be responders; 18 (34.6%) left the programme, and were considered to be non-responders. Considering the days of complete abstinence from alcohol, 36 patients stayed in treatment longer with the GHB-Disulfiram combination, 12 stayed for a shorter time and four for the same time. The results of this study seem to indicate a higher efficacy of the GHB-disulfiram association compared with GHB alone. Randomized controlled trials are now needed to verify this hypothesis.     

Repeated formaldehyde inhalation impaired olfactory function and changed SNAP25 proteins in olfactory bulb

Abstract

Background:

Formaldehyde inhalation exposure, which can occur through occupational exposure, can lead to sensory irritation, neurotoxicity, mood disorders, and learning and memory impairment. However, its influence on olfactory function is unclear.

Objectives:

To investigate the mechanism and the effect of repeated formaldehyde inhalation exposure on olfactory function.

Methods:

Rats were treated with formaldehyde inhalation (13·5±1·5 ppm, twice 30 minutes/day) for 14 days. Buried food pellet and locomotive activity tests were used to detect olfactory function and locomotion. Western blots were used to evaluate synaptosomal-associated protein 25 (SNAP25) protein levels in the olfactory bulb (OB) lysate and synaptosome, as well as mature and immature olfactory sensory neuron markers, olfactory marker protein (OMP), and Tuj-1. Real-time polymerase chain reaction (PCR) was used to detect SNAP25 mRNA amounts.

Results:

Repeated formaldehyde inhalation exposure impaired olfactory function, whereas locomotive activities were unaffected. SNAP25 protein decreased significantly in the OB, but not in the occipital lobe. SNAP25 also decreased in the OB synaptosome when synaptophysin did not change after formaldehyde treatment. mRNA levels of SNAP25A and SNAP25B were unaffected. Mature and immature olfactory sensory neuron marker, OMP, and Tuj-1, did not change after formaldehyde treatment.

Conclusion:

Repeated formaldehyde exposure impaired olfactory function by disturbing SNAP25 protein in the OB.     

Antioxidative stress response in workers exposed to carbon disulfide

Objective: To study the effects of carbon disulfide (CS₂) on antioxidative stress systems of exposed workers. Methods: Enzyme-linked immunosorbent assay (ELISA) and thiobarbituric acid test (BAT) were conducted on 67 exposed workers and 88 controlled ones in a viscose rayon factory to determine their serum cuprozinc-superoxide dismutase (CuZnSOD) and malonyldialdehyde (MDA) levels. Results: The average levels of CuZnSOD in workers exposed to CS₂ both above and below 10 mg/m³ were higher than those in the control group (P < 0.0001), showing some dose-effect and dose-response relationships. SOD levels increased when the exposure index (EI) was less than 300, and remained at a high level at the range of 300 to 900. When EI was higher than 900, SOD tended to decrease. Meanwhile, the serum MDA levels increased. Both CS₂ concentrations and exposure time contribute to the MDA levels. Conclusions: CS₂ exposure could influence the stress response of the oxidative-antioxidative system of workers. Increased SOD levels could be considered as the stress response of antioxidative system to CS₂ exposure in the early stages, and the influence of CS₂ on SOD might be bi-directional. SOD and MDA might become objective indices in workers' health surveillance. The role of these two indices in the intoxication mechanism still needs to be clarified. Received: 3 August 1999 / Accepted: 25 April 2000