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To determine relatively useful diagnostic procedures of carbon disulfide (CS2) poisoning in terms of validity and cost-effectiveness, several diagnostic tests are evaluated on 1,552 people by prevalence ratio (exposed/nonexposed), dose-response relationship, sensitivity and specificity, and the cost of the tests. Several symptoms with high kappa indices are found to be useful in various combinations, showing a consistent dose-response relationship and high exposed-nonexposed ratio. In clinicopathologic tests on functions of the kidney, liver and hematopoietic systems, eight items out of 22 have been shown to have significant dose-response relationship, mostly in liver function tests. A thorough dental examination failed to identify any useful indicator peculiar to the CS2 poisoning. Unlike Western people, the prevalence of coronary heart disease among Koreans was too low to be useful in the diagnosis of CS2 poisoning. Among four elective tests, i.e., Minnesota Multiphasic Personality Inventory (MMPI), Brain magnetic resonance imaging (MRI), nerve conduction velocity (NCV), and fluorescent angiography (FAG), the NCV appeared to be a more sensitive and specific test than the others are. Combinations of the tests improved the probability of diagnosing CS2 poisoning cases when any one test out of four was positive. Addition of other valid tests increased the probability of excluding non-cases. It was concluded that diagnosis of CS2 poisoning could be made validly and inexpensively if the diagnostic tests were carefully chosen step by step.

A 45-year-old nondiabetic man presented with features resembling diabetic triopathy. He worked in a rayon manufacturing plant and was exposed to toxic levels of carbon disulfide (CS(2)). Clinical abnormalities included peripheral and central nervous system abnormalities as well as retinopathy, dyslipidemia, cardiovascular disease, and nephrotic syndrome. He later developed focal sclerosing glomerulonephritis. The latter has not previously been described in cases of CS(2) exposure. Terminally, he developed end-stage renal disease and progressive dementia, both of which were thought to be consequences of CS(2) exposure earlier in life.

Carbon disulfide is a poison of particularly neotropic properties. In order to diagnose chronic occupational intoxication with carbon disulfide, a very careful examination of the central and peripheral nervous systems in required. The presence of subjective disorders only does not as yet provide grounds for diagnosing chronic intoxication. Organic changes like chronic encephalopathy or polyneuropathy after excluding the so called 'idiopathic' neurological diseases, may serve as a basis for certifying occupational disease.

Numerous occupational intoxications (acute, chronic and their sequelae) may affect the central nervous system and result in a wide variety of neuropsychiatric effects, ranging from subtle behavioural disturbances to overt psychosis. Chemicals causing such manifestations include many metals and organometals (Hg, Mn, Pb, Al, Sn), pesticides (organophosphates), compounds utilised in the industrial setting as solvents or intermediates (carbon disulfide, hydrocarbons and their halogenated derivatives), and combustion products (carbon monoxide). Some types of toxic insults may not be reflected in any clinical manifestation. However, this type of damage may render the brain more vulnerable to additional insult or accelerate physiological loss of neurones with ageing. Thus, occupational exposures to chemicals (Al, Pb, organic solvents) might be involved in the causation of neurodegenerative diseases--such as Alzheimer's disease--which are usually labelled as "idiopathic". A careful occupational anamnesis is crucial to diagnose work-related psychiatric manifestations and--consequently--to interrupt the toxic exposure, to start therapy, and to promote insurance compensation.

The abnormalities of cerebral vasoreactivity were evaluated in CS2 poisoning cases. In 34 retired workers with CS2 poisoning (case group) and 20 healthy individuals (control group), blood flow velocities were measured in the middle cerebral arteries (MCA) by transcranial Doppler. Compared with the control group, the case group showed lower mean values of blood flow velocities and pulsatile indices. The differences in CO2 reactivities of both groups were remarkable (1.10-2.19% decrease/mmHg CO2 for cases and 3.35-5.08 for controls). Multiple regression analyses were conducted to adjust the effect of age, sex, and exposure level (non-low-high exposure) to CO2 reactivity and pulsatile index. The exposure level was statistically significant in the regression model for CO2 reactivity of both MCA and for pulsatile index of the right MCA. Our study noted a decrease of CO2 reactivity and pulsatile index of cerebral vessels related with CS2 exposure. These findings suggested that CS2 exposure could lead to a decrease of cerebral vasoreactivities by the atherosclerotic change of cerebral vessels.

In the past 20 years, several outbreaks of neurotoxic disease due to occupational exposure have occurred in Taiwan. The most notorious outbreaks were 'Yu-cheng' due to contamination of polychlorinated biphenyls in cooking oil, lead poisoning in battery manufacturers and workers in a ship-scrapping yard, tile factory and battery recycling plants, and n-Hexane intoxication in press-proffers and ball-manufacturers. In addition, there were manganese intoxication in ferromanganese smelters, mercury intoxication in lamp-socket workers, carbon disulfide intoxication in viscose rayon workers and hydrogen sulfide intoxication in chemical synthetic plants. Although the incidence of occupational neurotoxic diseases has increased, the real incidence is probably still underestimated. The reasons for the underestimation include: 1) the education for workers in industrial hygiene is inadequate; 2) high risk workers are not screened well; 3) physicians are not well trained in early diagnosis of occupational diseases; 4) material safety data information is not readily available in the factories; and 5) the threshold limit values for toxic substances are relatively high in Taiwan, compared with other developed countries.

To understand central nervous damage after long-term exposure to carbon disulfide (CS2), 10 patients who had polyneuropathy with various neuropsychiatric symptoms in a viscose rayon plant were studied. Clinical and laboratory examinations including electroencephalography (EEG), brain computed tomography (CT), brain magnetic resonance images (MRI), and carotid duplex sonography were carried out. Clinically, headache, unpleasant dreams, memory impairment, fatigue, anorexia and emotional lability were common in these patients while 2 patients had stroke episodes. EEGs were all normal. Brain CT scan showed mild cortical atrophy in 3 and low density lesions in the basal ganglia in 3. Brain MRI studies also disclosed mild cortical atrophy in 4 and multiple lesions involving the basal ganglia and corona radiata in 4. Carotid duplex sonography revealed mild atherosclerosis with plaques (< 20% stenosis) of extracranial vessels in 6. However there was no significant difference in flow velocities and flow volumes in the extracranial carotid arteries between patients and the normal controls. Interestingly, 2 patients had multiple brain lesions in the subcortical white matter but without strokes. In conclusion, encephalopathy with possible strokes may occur after chronic exposure to CS2, as well as polyneuropathy. The lesions usually involve the basal ganglia and subcortical white matter. Furthermore, MRI study may detect brain lesions particularly in the subcortical white matter areas before the occurrence of stroke.

A mortality cohort study was carried out on 2,291 workers, including 169 women, with chronic occupational CS2 poisoning diagnosed during the years 1970-90. Information on vital status was available for 98.2% as of December 31, 1992. Mortality assessment was based on the standardized mortality ratio using the person-years method. The general population of Poland was the reference population. The number of subjects who died during the period of observation accounted for 658 men and 21 women. The analysis of mortality in male subjects showed statistically significant excess of deaths from the circulatory system diseases (SMR = 139), in this from ischaemic heart disease (SMR = 137), cerebrovascular disease (SMR = 188) and colon cancer (SMR = 233). Over a two-fold increased risk of death from diseases of the nervous system and sense organs, although statistically insignificant, was also observed. Among women a statistically significant risk of death from atherosclerosis was noted (SMR = 286). An elevated risk of death from the circulatory system diseases and from ischaemic disease (IHD) agrees with the results of some other cohort studies carried out in the viscose rayon workers. The increased mortality from malignant neoplasms is an unusual finding in cohorts of workers exposed to CS2. Our own data reported here showed a significantly increased mortality from colon cancer (9 cases). All these cases were noted in workers of the two oldest rayon plants and they require a detailed analysis. Further survey is also needed to elucidate the excess of deaths from the nervous system and sense organs diseases.

Artichoke, a new Bulgarian preparation based on the plant Cynara scolymus, was tested for influence on sympatho-adrenal system (SAS) activity in experimental inhalation exposure to carbon disulfide. This chronic (six-month) inhalation experiment was done on Wistar albino rats of either sex. Activity of SAS was assessed through excretion of noradrenalin and adrenalin. Findings indicated a phasic SAS response depending on concentration and duration of carbon disulfide exposure. With exposure to 30 mg.m3, SAS activity was observed to decrease in the second month, followed by increase in the fourth and sixth months. With exposure to 300 mg.m3, SAS activity was elevated over the whole period of study. Under the influence of the preparation artichoke at dosage 200 mg.kg-1, catecholamines, increased by carbon disulfide exposure, returned to normal. This trend was more marked for noradrenalin.

Two commonly employed solvents, n-hexane and carbon disulfide (CS2), although chemically dissimilar, result in identical neurofilament-filled swellings of the distal axon in both the central and peripheral nervous systems. Whereas CS2 is itself a neurotoxicant, hexane requires metabolism to the gamma-diketone, 2,5-hexanedione (HD). Both HD and CS2 react with protein amino functions to yield initial adducts (pyrrolyl or dithiocarbamate derivatives, respectively), which then undergo oxidation or decomposition to an electrophile (oxidized pyrrole ring or isothiocyanate), that then reacts with protein nucleophiles to result in protein cross-linking. It is postulated that progressive cross-linking of the stable neurofilament during its anterograde transport in the longest axons ultimately results in the accumulation of neurofilaments within axonal swellings. Reaction with additional targets appears to be responsible for the degeneration of the axon distal to the swellings.

Extrapyramidal signs are frequently observed in toxic diseases due to environmental and industrial chemical substances. The predominant manifestations are Parkinsonism and less frequently tremor. Parkinsonism has been described among the toxic diseases due to carbon monoxide, hydrogen sulfide, and hydrogen cyanide. In these diseases, Parkinsonism used to appear in the recovery stage from coma in the severe cases. This was also true in methyl alcohol poisoning. The extrapyramidal signs are usually symmetrical. Akinesia and rigidity are main features. Tremor is absent or mild. Levodopa and the other antiparkinsonian drugs are not so effective. Brain CT studies have revealed symmetrical low density areas in the globus pallidus and putamen. On the other hand, postural tremor is main neurological findings in the poisonings by inorganic mercury and tetraethyl lead. In general, tremor in the toxic disease is reported to be self-limited.

2-Thiothiazolidine-4-carboxylic acid (TTCA) is the accepted urinary indicator of occupational exposure to carbon disulfide. An extractionless automated column-switching procedure for the determination of this compound in urine was developed. The biological fluid is directly injected into the chromatographic system after dilution. A clean-up procedure is performed in an anion-exchange pre-column, with aqueous formic acid as eluent, followed by a transfer to a cyan-amino or amino analytical column in order to carry out analysis of TTCA under isocratic elution conditions, with a mixture of acetonitrile, water and formic acid as eluent, combined with ultraviolet detection. The detection limit of the method in urine is estimated to be 0.1 mg/l.

Some results of multiple epidemiological, clinical, electroneurophysiological, and psychological studies that reveal different types of neurotoxicoses are presented in this work. Under conditions of present-day industry, when a worker is exposed to concentrations close to but below the maximum allowable concentrations, or MAC values, of toxic substances, acute neurotoxicoses rarely develop, occurring perhaps only in catastrophies. Acute intoxications may be accompanied by mass hysteria, which impedes etiological diagnosis and prognosis. Vegetative polyneuropathy is the most common type of chronic intoxication where central vegetative disorders sometimes precede the peripheral ones. Clear forms of intoxication caused by neurotrophic poisons show stable torpid development during subsequent phases of a disease despite the absence of contact with the toxicant.

Sixteen former rayon viscose workers were investigated four years after the exposure to carbon disulfide was discontinued. Median age was 58 years (range 43-65 years), median exposure time was 17 years (range 10-35 years). Encephalopathy was diagnosed in altogether 14 workers. To further explore pathophysiological mechanisms, cerebrovascular investigations were employed. Doppler ultrasound examination of the precerebral vessels in 15 workers showed a slight stenosis of the left internal carotid artery in one. Regional cerebral blood flow investigation (rCBF) with single photon emission computerized tomography (SPECT) with Xenon-133 gas was performed in 14. There was no significant difference from a control group. Regional side-to-side asymmetries beyond reference limits were demonstrated in eight workers. The abnormalities were modest, but may indicate a tendency toward focal blood flow disturbances in workers with long-term exposure to carbon disulfide.

In the group of 37 patients with chronic carbon disulphide (CS2) intoxication manifested by encephalopathy, polyneuropathy or psycho-organic syndrome and complaining for vertigo, a statokinesiometric test was performed with open and closed eyes, and with visual stimulation. Basic test parameters of stabilograms and statokinesiograms were compared with standard values of the control group. Results of the test were additionally verified by electronystagmography with the recording of spontaneous, positional, optokinetic and post-rotatory nystagmus as well as the eye-tracking test. The statokinesiometry revealed postural stability disorder in 72.9% of patients. Balance disorders detected by means of this test showed high compatibility with results of electronystagmography which confirmed damage of the central part of vestibular system due to CS2 intoxication.

The aim of the study was to determine the similarities and differences between the groups of dysfunctions detectable using psychologic tests in workers exposed to metallic mercury, inorganic lead and carbon disulfide. The study groups included male workers examined in the Clinic of Occupational Diseases of the Institute of Occupational Medicine in Lodz. The subjects were supposed to the chronically intoxicated with Hg (27 persons), Pb (40 persons) and CS2 (40 persons). A wide variety of tests was used to examine reference groups matched appropriately according to sex, age and level of education. The comparative analysis of results showed that the range and extend of a decrease in psychic functions depend on the type of a neurotoxic agent. The most serious disorders (frequently those of organic brain disease type) were found in subjects exposed to CS2. Exposure to metallic mercury resulted in functional disorders of the psychic sphere, while exposure to inorganic lead caused some minor functional changes. The results of the psychological examination of the subjects may be useful both for individual analysis and for screening.

Cell composition of the cortical plateau, medullary cords and lymphoid nodules++ has been determined in 180 Wistar rats in 2 weeks, 1 and 3 months after inhalation of carbon disulfate vapour for 2, 7 and 14 days in a maximum permissible concentration (1 mg/m3) and in the control group. In 2 weeks after cessation of the vapour inhalation activity of lymphocytopoiesis, blastopoiesis, cell differentiation decreases, macrophagal and plasmocytic reactions are weakly manifested. In 1 month certain signs of compensatory-adaptive reaction are noted; they are seen as increasing proliferative processes and activation of cell differentiation in the lymphoid nodules++ and a sharp plasmatization of the medullary cords. In 3 months after the experiment retardation of lymphocytopoiesis is still definitely manifested in the cortical plateau and medullary cords and essential destructive processes are observed against the background of local increase of the functional activity of the lymphoid nodules++.

Central nervous system dysfunction among CS2-exposed workers was studied by measuring short latency SSEPs and VEPs. The examinations were done in 40 men. Chronic CS2 intoxication was diagnosed in 21 of them. Latency of N19, N11, N20 of somatosensory evoked potentials and latency of P100 wave of visual evoked potentials were statistically significant longer in CS2 exposed group in comparison with controls. The amplitude of N20 SSEPs was also significantly higher. Increase of N20 amplitude (33 persons) and elongation of its latency (25 persons) were frequent abnormalities of SSEps. In individual assessment of VEPs, most frequent were: abnormal difference in interocular latency of P100 (26 persons) and elongation of P100 latency (25 persons). In the analysed SSEPs and VEPs parameters there was no significant difference between two clinical groups. The authors conclude that the CS2--neurotoxic effect leads to impairment of the peripheral and central part of the somatosensory pathway, as well as to central dysfunction of the visual pathway.

Auguste-Louis Delpech (1818-80) has been remembered principally as the author of the first detailed description of the serious consequences of exposure to carbon disulphide. A close reading of his work suggests that his reputation has been seriously undervalued. The subsequent development of occupational psychiatry, with its emphasis on the distinction between the organic and the functional, may be traced through publications on carbon disulphide. It is argued that a contemporary approach to occupational psychiatry is long overdue.

A visual and computer-assisted analysis was made of basic brain biological function in 45 EEG recordings of alpha waves alone or mostly alpha waves. The study revealed abnormal frequency of alpha waves in patients with chronic alcoholism (60%) and in people chronically exposed to carbon disulphide (73.4%). The abnormalities most probably reflect dysfunction of the CNS.

The relationship between parameters of visually evoked potentials (VEPs) and the results of a psychological test assessing the speed of motor reaction to visual stimuli was examined in 21 patients with chronic carbon disulphide intoxication. Correlations obtained suggest cerebral disfunction of the visual pathway and diminished ability to transform visual information to motor reaction at the level of the cortical association centre.

The studies covered 32 workers chronically exposed to CS2 and controls. In all subjects diethyldithiocarbamaturia was evaluated and J131 labelled Bengal Rouge decay half-time was determined. The studies indicated statistically significantly lower DDC excretion in CS2 exposed workers, as compared to controls. On the other hand no statistically significant differences were found at the Bengal rouge decay half--time in blood. The above studies suggest that the disulphuran metabolic route was impaired prior to the occurrence of the changes in liver blood flow of CS2 exposed workers.

In the studies carried out lipids content in blood serum and aorta wall as well as morphological changes in coronary vessels of CS2 exposed rats have been evaluated. The 10-month-exposure to CS2 at a concentration of 0,8--0,9 mg/l has been found to result in: (1) increased concentration of total and free cholesterol, cholesterol esters, triglycerides and phospholipids in blood serum; (2) increase in total cholesterol and significant rise in the level of cholesterol esters in the aorta wall; (3) a relative increase in serum VLDL, LDL and decrease in HDL fraction. Histological estimation has demonstrated in serial sections of hearts of the CS2 exposed animals thickened walls of left coronary artery branches with no lipid deposits. In two animals focal steatosis of aortic bulb wall and aortic valves and lipids droplets in endothelium of ascending aorta and coronary vessels have been found.

Disulfiram in generally accepted maintenance doses in alcoholism may produce a rather severe polyneuropathy. In addition to the 39 literature cases, 5 personal patients were examined. Detailed clinical findings are given and the frequent permanent sequelae are emphasized. In 2 patients sural nerve biopsies were studied (including electromicroscopical examination) revealing a primary axonal lesion. In the treatment of alcohol addiction one should be aware of this complication.

To clarify the pathological difference of retinal changes between carbon disulfide (CS2) and diabetic retinopathies, fluorescein fundus angiograms of 92 workers with CS2 retinopathy (Group I) were compared with those of 37 cases with diabetic retinopathy (Group II) and 40 workers who had not been exposed to CS2 (Group III). The results were: 1) Ellipsoid or loop-shaped microaneurysms were observed in 25% of Group I, and in 5% of Groups II and III. 2) Fluorescein leakage from vessels was observed in Group II, but not in Groups I and III. 3) An avascular area of the retina was observed in Groups I and II. The avascular area in CS2 retinopathy was small and local and showed no tendency of enlarging. 4) Atrophic/degenerative changes of the pigmentary epithelium were observed in 40% of Group I, 11% of Group II and 15% of Group III.

Quantitative assessment of nervous system function is essential in characterizing the nature and extent of impairment in individuals experiencing symptoms following workplace exposure. In recent years, the application of standardized neuropsychological tests to the evaluation of exposure to toxic industrial substances has significantly increased the understanding of the effects of these compounds. Within this review, the specific toxic neuropsychological effects of lead, carbon disulfide, trichloroethylene, perchloroethylene, mercury, styrene, and pesticides are discussed in detail. These discussions draw on our clinical experience with patients exposed to these substances as well as material from the medical literature. Factors affecting the utilization of these tests in occupational settings are also considered.