Renal injury following long-term exposure to carbon disulfide: analysis of a case series.

BACKGROUND: To investigate the clinicopathological characteristics of renal damage caused by long-term exposure to carbon disulfide (CS2) in nine patients. METHODS: All the patients underwent ultrasound-guided renal biopsy. All specimens were examined by light microscopy and immunohistochemistry (IHC). Samples form one patient were further analyzed using transmission electron microscopy. RESULTS: Similar pathological changes were observed in all patients, but the degrees of lesions were different. All cases had moderate to severe nodular mesangial hyperplasia; among these, type "Kimme1stie1-Wi1son" (K-W nodule for short) was observed in four cases, type "K - W nodule" refer to nodular hyperplasia of mesangial membrane like letter K or W. four cases had proliferative extracapillary glomerulonephritis (GN), while there were no concomitant changes in one patient. Besides, six cases had diffuse basement membrane thickening, focal segmental sclerosis or bulbar sclerosis; two cases had diffuse glomerular sclerosis, and one case had focal segmental capillary hyperplasia. Moreover, all patients had renal tubular atrophy/interstitial fibrosis with less to moderate chronic inflammatory cell infiltration, as well as renal arteriosclerosis. IHC showed that the depositions of IgA, IgM, C3d, C4d, C1q and Fib were not specific; while IgG, type III collagen, Fibronectin, Amyloid A, Igκ, Igλ, HBsAg and HBcAg were all negative. CONCLUSION: Diffuse nodular mesangial hyperplasia/sclerosing glomerular nephropathy is characterized by nodular mesangial hyperplasia with type "K-W nodules" formation, which we speculate is a special pathological manifestation of renal damage caused by carbon disulfide (CS2).

[Clinical characteristics of the patients with occupational chronic carbon disulfide poisoning in a chemical fiber factory of Nanjing].

OBJECTIVE: To analyze the clinical characteristics of 267 cases with occupational chronic carbon disulfide (CS(2)) poisoning and to provide the basis for revising the items of periodical medical examination of workers occupationally exposed to CS(2). METHODS: The subjects of present study were 267 patients with mild CS(2) poisoning diagnosed according to "Diagnostic Criteria of Occupational Chronic Carbon Disulfide Poisoning (GBZ4-2002)" from April in 2006 to May in 2010. All patients were from the same chemical fiber factory. When a subject was diagnosed as patient with CS(2) poisoning, who should interview with questionnaire which included the illness and occupational history, symptoms, individual habits. The physical examination, nervous test, cardiovascular test, biochemical test and electromyogram were performed. RESULTS: The rate of decreased motor conduction velocity was 87.3% (233/267 roots). The highest detection rate of slowing conduction velocity was the common peroneal motor nerve which was 48.6% (138/248 roots) and the second was median motor nerve with delay rate of 37% (155/419 roots). The main symptoms of the patients were neurasthenia, numbness and paresthesia. The rates of abnormal achilles tendon reflex and knee jerk reflex in patients were were 79.4% and 49.8%, respectively. The detected rates of patients with ST-segment changes and hypertension were 19.1% and 27.5%, respectively. The rates of hypertension, systolic pressure and diastolic pressure were 27.3%, 22.5% and 21.1%, respectively. The rates of lactate dehydrogenase (LDH), triglycerides (TG) and low density lipoprotein (LDL) were high. The detected rates of urine acid, indirect bilirubin and total bilirubin in male patients were higher than those in female patients. In addition, the abnormal detected rate of urea nitrogen and indirect bilirubin increased with exposure years. CONCLUSION: Occupational chronic CS(2) poisoning mainly affects the nervous system, as well as liver and kidney function. Detecting the median and common peroneal motor nerve conduction velocities could be the screening indicators for the peripheral nerve injury induced by CS(2) in the occupational exposure population during the periodical occupational medical examinations.

[Prophylaxis of carbon bisulphide poisoning effects on lipid component of erythrocyte membrane in experiment].

Preventive injection of "Kalifen" extract of high cranberry before and during intoxication with carbon bisulphide appeared to preserve lipid component of RBC membrane in rats.

[Prevention of abnormal physiological and biochemical characteristics of red blood cells in carbon disulfide intoxication].

Experimental studies were conducted on 4 groups of 10 rats each: 1) intact animals (a control group); 2) inhalation of carbon disulfide at a concentration of 2.0 mg/m3 for 7 days; 3) prophylactic administration of the hepatoprotective agent Legalon (100 mg/kg of total polyphenols), followed by carbon disulfide inhalation for 7 days; 4) prophylactic administration of the biologically active additive Kalifen (100 mg/kg of total polyphenols for 7 days), followed by carbon disulfide inhalation. Animal survival after carbon disulfide inhalation was 80%; preadministration of Legalon or Kalifen increased survival up to 100%. Carbon disulfide inhalation was attended by abnormal size features of red blood cells, impairments in the antioxidant defense system and the ratio of phospholipid fractions to neutral lipids. Preadministration of Legalon or Kalifen before inhalation contributes to less abnormalities in the study physiological and biochemical parameters of erythrocyte membranes.

Metabolic syndrome in carbon disulfide-poisoned subjects in Korea: does chemical poisoning induce metabolic syndrome?

OBJECTIVE: Mass carbon disulfide (CS(2)) poisoning was reported at a viscose rayon factory in Korea. We evaluated the association between CS(2) poisoning and the prevalence of metabolic syndrome. METHODS: The cases (n = 170) involved CS(2)-poisoned subjects, who participated in a health examination conducted at a hospital in Korea in 2005. The controls (n = 170) were selected randomly from the participants in the third Korean National Health and Nutrition Examination Survey. Metabolic syndrome was defined as having at least three of following metabolic abnormalities: abdominal obesity, elevated triglyceride, reduced high-density lipoprotein cholesterol, elevated blood pressure, and elevated fasting glucose levels. RESULTS: After adjusting for covariates (age, gender, education, marital status, alcohol consumption, and smoking), CS(2)-poisoned subjects had an increased risk of metabolic syndrome (prevalence ratio 1.57, 95% CI 1.25-1.98). CONCLUSIONS: The findings suggest that CS(2) poisoning may increase the risk of metabolic syndrome.

[Alterations of microtubule and microfilament expression in spinal cord of carbon disulfide intoxicated rats].

OBJECTIVE: To investigate whether the alterations of microtubule and microfilament expression are responsible for the neurotoxicity of carbon disulfide. METHODS: Wistar rats were administered with carbon disulfide by gavage at a dosage of 300 or 500 mg/kg for continuous 12 weeks (five times per week). Spinal cords of carbon disulfide-intoxicated rats and their age-matched controls were Triton-extracted and ultracentrifuged to yield a pellet and a corresponding supernatant fraction. Then, the contents of alpha-tubulin, beta-tubulin, and beta-actin in both fractions were determined by immunoblotting. In the meantime, their mRNA levels in spinal cords were quantified using reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: In the supernatant fraction, the contents of beta-tubulin and beta-actin in both treated groups increased significantly (P < 0.01) the content of beta-tubulin increased by 141% and 158% respectively, and the content of beta-actin increased by 19% and 32% respectively. In the pellet fraction, the content of beta-tubulin in both groups increased by 107%(P < 0.01) and 118%(P < 0.01) respectively, and the others keep unaffected. In the meantime, the levels of of mRNA expression of beta-tubulin and beta-actin gene were elevated consistently in CS(2)-treated groups (P < 0.01) the levels of mRNA expression of beta-tubulin increased by 207% and 212% respectively, and the levels of mRNA expression of beta-actin increased by 94% and 91% respectively. CONCLUSION: Carbon disulfide intoxication results in alternations of microtubule and microfilament expression, and the alternations might be related to its neurotoxicity.

Electrocardiographic abnormality for workers exposed to carbon disulfide at a viscose rayon plant.

OBJECTIVE: This study investigated electrocardiography (ECG) manifestations for male workers with carbon disulfide exposure at rayon manufacturing plants. METHODS: A total of 251 men in the exposure group and 226 administrative clerks in the reference group received physical examinations and completed questionnaires. RESULTS: The prevalence of ECG abnormalities was much higher in the carbon disulfide exposure group (25.9%, n = 65) than in the reference group (2.7%, n = 6), with an odds ratio (OR) of 12.8 (95% confidence interval [CI] = 5.4-30.2). The foremen were at the highest risk of abnormal ECG (OR = 20.6, 95% CI = 6.5-65.2), followed by filament-spinning workers (OR = 14.2, 95% CI = 5.7-35.3), viscose-manufacturing workers (OR = 11.3, 95% CI = 4.3-30.1), and carbon disulfide-manufacturing workers (OR = 8.1, 95% CI = 2.7-25.6). The multivariate logistic regression analysis based on cumulative exposure index also showed a dose-response relationship with the exposure, and the risk of ECG abnormality could be initiated at the exposure history of 31 to 57 year-ppm with an OR of 7.2 (95% CI = 1.5-36.7). CONCLUSIONS: In general, the ECG abnormalities observed in workers at the permissible exposure level of carbon disulfide implicate the importance of environmental control of the chemical and of workers' education in exposure prevention at work.

Disulfiram toxicity and carbon disulfide poisoning.

The author compared the neurotoxic effects of disulfiram with those of carbon disulfide, a disulfiram metabolite. The results suggest that carbon disulfide is responsible for the behavioral and neurological side effects of disulfiram. If this is so, then some other toxic effects of carbon disulfide, including parkinsonism, choreoathetosis, and thalamic syndrome may follow the ingestion of more than 5 g of disulfiram by adults, and individuals receiving as little as 125 mg of disulfiram per day may be at a three- to four-fold greater risk for arteriosclerotic cardiovascular disease than a comparable population not receiving the drug.

Carbon disulfide nephropathy.

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.

Clinical and electrophysiological studies of carbon disulphide polyneuropathy.

A clinical and electrophological study was performed on 30 patients with chronic carbon disulphide poisoning. Although the measurements of motor conduction velocity and of terminal latency were within the normal range in the subclinical stage, estimation of nerve excitability threshold showed distal motor hypoexcitability, thus proving a very effective means for the early detection of carbon disulphide polyneuropathy. The distal muscle fatigue found in 35% of patients was confirmed by the decrement (more than 10%) in the amplitude of muscle evoked potentials in the abductor digiti minimi muscle in response to repetitive stimulation of the ulnar nerve. Association of the above findings with the significant electrophysiological changes, viz., decrease in the amplitude of sensory evoked potentials on stimulation of the digital fibres, mild slowing of sensory conduction velocity in the peripheral nerves, and decrease in the amplitude of evoked potentials in the distal muscles, suggest that the carbon disulphide polyneuropathy would be underlain by a primary distal axonopathy.

Cerebrospinal fluid cells and proteins in patients occupationally exposed to organic solvents.

Cerebrospinal fluid (CSF) cells and proteins were determined for 33 patients exposed to industrial organic solvents. A lymphoid reaction, i.e., a pathologically elevated number or percentage of enlarged lymphoid cells was observed in one-third of the patients, more often in patients with chronic intoxication (40%) than in those currently exposed to organic solvents (32%). An almost significant decrease of small lymphocytes in the CSF was observed among patients who had a past history of chronic solvent intoxication but no recent exposure. No cytological evidence of tissue destruction was found. Signs of slight blood--CSF barrier damage occurred in 5 (23%) of the currently exposed patients, but intrathecal IgG synthesis was not observed. Increased cellular activity in the CSF was also accentuated in principal component analysis. The results suggest slight nonspecific immunoactivation in the central nervous system of subjects exposed to organic solvents.

Effects of acute CS2 intoxication on protein metabolism in rat brain.

The effect of acute CS2 exposure on the rat brain protein metabolism was studied with control and phenobarbitone pretreated adult male rats 1, 4 and 46 h after exposure. Increased activity of acid proteinase was detected in both test groups 1 and 4 h after exposure and it was accompanied by changes in 14C-labelled leucine turnover as well as in RNA content. The changes were more conspicuous in cerebellum than in brain in both test groups while phenobarbitone pretreatment modified the brain response towards intoxication. This modification probably represents inherent effects of barbiturate on brain protein metabolism as well as altered metabolism of CS2. The activities of creatine kinase and nonspecific cholinesterase displayed only subtle changes as assayed in cerebral homogenate and serum. Thus a single acute CS2 intoxication apparently causes definitive transient changes in brain protein metabolism; serum enzyme determinations may not reflect the magnitude of these changes.

The content of high-energy phosphates and ultrastructure of mitochondria in the brain of rats exposed to carbon disulphide.

Rats were exposed to carbon disulphide (CS2) continuously for 12 h or for 10 months, at concentrations of 2.4 mg/l air and 0.8 mg/l air, respectively. No changes in the brain content of ATP, ADP and AMP were found in rats after chronic exposure, whereas the content of ATP in the brain of rats acutely poisoned with CS2 was significantly higher (21%) accompanied by decrease in the content of ADP (10%) and AMP (45%). The biochemical changes were accompanied by ultrastructural changes of mitochondria, particularly those in the cerebellar perikaryons.

Combined exposure to carbon disulfide and sulfuric acid simultaneously increases the risk of hand dermatitis in rayon industry.

OBJECTIVE: To evaluate the association between hand dermatitis (HD) and occupational exposure to CS(2) and to determine whether combined exposure to CS(2) and H(2)SO(4) exhibits a higher risk of HD. METHODS: In all, 110 subjects from a rayon factory were recruited and their exposure was classified into CS(2) exclusively, H(2)SO(4) exclusively, combined exposure, and nonexposure control based on workers' job characteristics. A dermatologist was designated in the diagnosis of HD on palm and dorsal sites for each subject. Other confounding factors including detergent, glove wearing, and participation in wet work were determined using a person-to-person questionnaire interview from 37 randomly selected subjects. RESULTS: Significant elevated odds ratios (ORs) for HD were found in CS(2) exclusively (44.8, P < 0.01) and combined exposure (49.0, P < 0.001) compared with control. Dose-response trends of ORs for HD were found across control, single exposure, and combined exposure for both CS(2) and H(2)SO(4). CONCLUSIONS: HD could occur resulting from occupational exposure to CS(2) alone. This study was unable to affirm that the exposure to H(2)SO(4) alone is associated with HD due to limited H(2)SO(4) exposure subjects. The combined exposure to both CS(2) and H(2)SO(4) simultaneously could increase the risk of HD. The control remedy in preventing dermal contact with either CS(2) or H(2)SO(4) among the rayon workers should be performed immediately.

Disulfiram polyneuropathy.

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.

Clinical course in patients with chronic carbon disulfide polyneuropathy.

The natural course of clinical manifestations and electrophysiological changes were studied in six patients with carbon disulfide (CS(2)) induced polyneuropathy. All of the six patients worked in the cutting-machine department of a viscose rayon plant. The environmental monitoring was also conducted in the initial stage and followed up 3 years later. In the 3-year follow-up period, the neurological symptoms and signs persisted. The highest concentration of CS(2) in the cutting machine where these patients worked was about 100-200 ppm. Three years later, the highest concentration was decreased to between 10 and 20 ppm in the cutting machine of the new production line after the engineering control had been improved. Nerve conduction velocity (NCV) studies revealed persistent abnormality in motor and sensory NCVs. Although, a tendency to improvement was noted, it did not reach a statistical significance except for conduction velocity of sural nerve in sensory NCV. Sural nerve biopsy from one patient, 2 years after diagnosis showed degeneration of both axon and myelin and a predominant loss of large myelinated fibers. A remyelination process was also noted. We concluded that CS(2) intoxication may induce a persistent damage to the peripheral nerves even after CS(2) exposure had ceased for 3 years.

Parkinson's disease and occupational exposure to organic solvents, agricultural chemicals and mercury--a case-referent study.

Parkinson's disease has been associated with heavy occupational exposure to carbon disulfide, and this solvent, as well as other organic solvents, may cause neurotoxic effects. Therefore, the hypothesis was raised that organic solvents in general may be associated with Parkinson's disease. A case-referent study design was applied, and some other suspected exposures were studied as well. The diagnosis registers of two Swedish hospitals were used as the source of subjects. Male in-patients with Parkinson's disease (the cases) or subarachnoid hemorrhage (referents), with symptom appearance between 35-69 a of age and residence in the vicinity of the hospitals, were included in the study. Occupational exposure to the chemicals under study were determined from questionnaire answers of 91 cases and 75 referents. No differences in exposure frequency to organic solvents in general were observed, but three cases had been exposed to carbon disulfide compared to none of the referents. Six cases, but only two referents, had been exposed to mercury, and further exploration of a possible association between exposure to mercury and Parkinson's disease is recommended. The outcome of the study does not support the hypothesis that occupational exposure to organic solvents in general increases the risk of Parkinson's disease, but the confidence intervals of the odds ratios do not rule out such possibilities.

Ten-year coronary mortality of workers exposed to carbon disulfide.

Two cohorts, one comprising 343 viscose rayon workers exposed for at least five years to carbon disulfide (CS2) and the other made up of 343 nonexposed men, were followed from 1967 to 1977 with respect to coronary heart disease (CHD) mortality. In the examination in 1967 known risk factors of CHD were controlled; only blood pressure was slightly higher in the exposed group. The difference was considered a result of exposure. Five exposed and eight nonexposed men had experienced a previous clinical myocardial infarction. The total mortality was 48 (14%) in the exposed group and 31 (9%) in the compeer group (p congruent to 0.05); 29 exposed and 11 nonexposed men had died from CHD (p less than 0.01), and 5 exposed and 1 nonexposed from other cardiovascular causes (p = 0.1). All coronary deaths occurred in the age interval 40 to 69 years. The estimated risk of death from CHD for this 30-year age span, assuming no competing risks of death, was 31.9% for the exposed cohort against 13.3% for the compeers. A multivariate analysis yielded age, raised blood pressure, and exposure to CS2 as prominent risk factors. The contributory risk caused by past occupational CS2 exposure seemed to increase the already notoriously high risk of CHD mortality among Finnish men.