Reports of inorganic mercury intoxication in Korea began in 1985 when a woman employed at a thermometer manufacturer was diagnosed as having an organic mental disorder (15). She was 16-yr-old and had been working in the inspection and packing division. Two months later after she started working for the thermometer manufacturer, she showed erythematous rushes on her skin. Subsequent to that symptom, she developed hand tremor, convulsion and dysarthria. During the mental examination, she was diagnosed with depression, anxiety and generalized cognitive dysfunction, such as memory loss and decreased concentration.

In 1987, an epidemic from a fluorescent lamp manufacturer occurred when 18 out of the 25 workers at the manufacturer tested for more than 0.03 µg/mL of serum mercury concentration (1). At the factory, four cases of chronic mercury poisoning were reported (17). The workers had been working between 15 months and 7 yr, showing symptoms of tremor, dysarthria, anxiety, memory loss, decreased concentration, insomnia and gingivitis. After chelating treatment with D-penicillamine and British Anti-Lewisite (BAL) in the hospital, all workers recovered. A second report of inorganic mercury poisoning from the company included 6 male patients (16, 18), with 2 patients overlapping with the initial report (17). In the second report, the exposure level of airborne mercury was 0.005-0.144 mg/m³ (16).

In June 1988, a 15-yr-old boy, who had been working for 2 months in a precision instrument manufacturer located in Seoul, died (2). He had shown severe neuropsychiatric symptoms: anxiety, hallucination, inappropriate affection, articulation impairment, hand tremor, convulsion, insomnia and memory loss. The airborne concentration of mercury was 0.02-0.24 mg/m³. After this accident, as serious concerns began to be expressed by non-governmental organizations, the epidemiological investigation of mercury-exposed workers was conducted by Korea University on the request of the Ministry of Labor (5). During the investigation, special medical examinations were performed on 134 workers in 18 mercury-handling workplaces, and 27 (20%) were found to be suffering from mercury poisoning.

There were no more outbreaks of mercury poisoning until three cases of inorganic mercury intoxication were discovered in a waste treatment company in 2000 (19). Workers had extracted a silver compound from waste radiography film using inorganic mercury for about 1 month. The exposure level of airborne mercury was 0.03-1.235 mg/m³. All three workers showed pain in the arms and legs, memory loss and peripheral neuritis and had abnormal findings on magnetic resonance imaging (MRI). One showed hallucination and delirium and was diagnosed with brief reactive psychosis.

Nine out of 13 inorganic mercury poisoning cases showed neurological or psychiatric symptoms and signs (Table 2). Some showed the classic neurological signs of mercury intoxication, such as irritability (2 cases) and hand tremor (6 cases). Other symptoms, such as skin lesion, stomatitis and weight loss, were also reported in some cases.

Occupational carbon disulfide intoxication was diagnosed in 1981 (5) for the first time. In 1987, more employees who had worked for the previous 10 yr in the spinning process, making artificial silk thread from pulp dissolved in a carbon disulfide solution (3, 20-22), were diagnosed with carbon disulfide poisoning, turning into an outbreak that numbered a total of 950 victims by 2008 (4). The company was built by used machines imported from a viscose rayon company in Japan and started operation at 1966 (4). At the time, the number of employees reached 1,500 in the company but dwindled to 811 by the time it was closed down in 1993 (5).

The major characteristics of the carbon disulfide poisoning cases that developed in 1987 were CNS and PNS symptoms, which was well-described in 8 patients (3). Six of the 8 patients showed dysarthria, 5 showed hemiparesis, 5 showed organic brain syndrome, and all 8 workers showed polyneuropathy. The exposure duration was 6 to 18 yr (Table 3). The mean exposure level of the air concentration of carbon disulfide in the company was reported at 1.2-23.1 ppm (21). One study that evaluated the ex-employees of the rayon manufacturer reported that 61.5% and 15.4% of workers among the 117 chronic carbon disulfide poisoning patients had neurological disorders and psychiatric disorders, respectively (22).

Chronic toxic encephalopathy caused by mixed solvent was reported in 10 cases (7, 19, 24, 25, 29-31), including 3 female and 7 male workers (Table 4). All patients had been exposed to mixed solvents. However, toluene and trichloroethylene were the main components of the solvents. Because the exposure levels of the cases were measured only after the patients had been found and the work enviromment had been improved, the actual exposure level of the workers could be underestimated. Out of 10 cases, 4 patients could be classified as ISW category 3, and 2 patients could be classified as ISW category 2B. Two showed cerebellar syndrome and severe ataxia. One case of ISW category 3 from a footwear manufacturer showed a severe atrophic lesion on a brain MRI and had been exposed to a very high level of solvents--11.2 on the mixed solvent index (the reference level is 1.0).

All of 10 cases of methyl bromide intoxication were found in fumigation workers (19, 23-25) who had infused the pesticide into covered woodstacks or a container in which agricultural goods had been kept (Table 5). The first case of methyl bromide intoxication, found in 2000, was a 20-yr-old man, working for fumigation for two months. Subsequently, three cases of methyl bromide intoxication were reported before 2001. In 2008, an outbreak of methyl bromide intoxication was reported in which 6 workers from a fumigation company showed CNS and PNS symptoms.

The airborne concentration of methyl bromide in the total of 10 cases ranged from an undetected level to 15.1 ppm as the Occurpational Exposure Level of Korea. In one company, where the short-term exposure level (STEL) was measured, the exposure level reached 28.8 ppm. The levels of bromide in serum and urine of the 10 cases were 11.7-39.6 mg/L and 2.6-94.6 mg/L, respectively. All but one worker showed gait disturbance. Two showed objective findings of polyneuropathy from electromyography. Five showed mild to diffuse lesions on a brain. The loci of brain lesions in the MRI were the cerebellum, midbrain, globus pallidus, olive, pons, periaqueductal white matter region, 4th ventricle and corpus callosum (Table 5).

A patient suffering from organotin poisoning (26, 27) had been working as a tank cleaner for several different companies in the previous eight years. He had cleaned a tank containing dimethyltin for four days. A day after finishing the job, he suffered decreased memory, behavioral changes and progressive mental deterioration when he arrived at the emergency room. The result of spinal tapping was negative, but on the fourth day of admission, he deteriorated into a state of coma along with metabolic acidosis and severe hypokalemia. High levels of DMT and trimethyltin (TMT) were detected in a highly sensitive urine analysis.

Acetonitrile is the simplest organic nitrile and used in various industries. It can be metabolized to produce hydrogen cyanide, which is the source of the toxic effects (32). Two male pharmaceutical workers (37 and 38 yr old) had been exposed to acetonitrile dust during polymerization process since 1994 and were diagnosed with acute acetonitrile intoxication in 1995 (19). Both felt stiffness in their legs and arms, beginning after a few days of working at the process. In January 1995, they felt dizziness and severe fatigue after the polymerization. The next morning, both felt stiffness on the tongue, experienced nausea and vomiting and talked deliriously. They were admitted to the hospital and diagnosed with chemical-induced CNS disorder.

Carbon monoxide intoxication was found in an apartment building guard (male, 58 yr old), who had to sleep in the boiler room where the carbon monoxide was generated. His duties were the operation of the boiler and other security jobs in the apartment building. He was working in 24-hr shifts. The exposure level of carbon monoxide, which was measured in the outlet of the duct through which the exhausted gas was ventilated, was 103.2 ppm. In January 2006, he was discovered in the boiler room in an unconscious state. He was admitted to hospital and given a conservative treatment. One week after he discharged, he showed cognitive loss and motor dysfunction. He was admitted hospital again and diagnosed with delayed hypoxic encephalopathy (28).

Fifteen cases of peripheral neuritis were reported by 2009 (Table 6). All cases but one of n-hexane-induced peripheral neuritis were reported from workers in the electronics industry, such as a LCD-frame manufacturer and a cellular phone manufacturer. A cleaning process using n-hexane was the most common job in these cases. Eight cases (from cases numbered 6 to 13) were an outbreak from an LCD frame manufacturer in 2005. Eight female workers whose job had been cleaning the LCD frame were discovered to have been exposed to 114.4-281 ppm of n-hexane; they were diagnosed with peripheral neuritis (35).

In 1999, the subclinical effects on nerve conduction velocity (NCV) were measured in the workers exposed to low-level n-hexane (8). The results from this study showed that chronic (mean exposure duration=15 yr) low-level (mean exposure level=23 ppm) exposure to n-hexane caused subclinical impairment of the peripheral nervous system.

Neurological disorders other than peripheral neuritis were anosmia (24, 37, 38), sixth cranial nerve palsy (19) and reflex sympathetic dystrophy (28). Anosmia was reported in workers using mixed solvent at a bicycle manufacturer (24), in two workers who were exposed to chloride at a train manufacturer (37), and in a worker who was exposed to metalworking fluid during the heat treatment of metal processing (38).

A patient suffering from reflex sympathetic dystrophy was exposed to pesticide while spraying it on a garden. He was using the organophosphorous pesticide for 3 days and accidentally splashed it on his body. One week later, he experienced decolorization of the skin, chronic pain and atrophy of the arm muscle (24).

The classical description of Mn-induced Parkinsonism was in a report of Mn-mining workers at a refinery who were exposed to high levels of manganese (39). In Korea, however, the first report of Mn poisoning was reported from a welding rods manufacturer from crushing ferromanganese (40). Three cases of Mn-induced Parkinsonism, showing postural instability, gait difficulty and bradykinesia, had been working at the company for one to three years (Table 7).

After the report, most of the Mn-induced Parkinsonism cases in Korea were found in welders (10, 19, 28, 31). In 1998, three welders with more than 10 yr of welding experience were diagnosed with Mn-induced Parkinsonism (10). They did not match the classical appearance of Mn intoxication; however, their brain MRI showed high signal intensity in the basal ganglia area on T1-weighted film. Because welders were not considered at risk for serious Mn exposure before this report, large concern for Mn toxicity in Korean workers began, especially in the welders' union. The Ministry of Labor asked OSHRI for a nationwide investigation to clarify the clinical significance of increased signal intensities on T1-weighted MRI. The investigation examined 750 workers from welding, alloy furnace and welding-stick manufacturing. The neurobehavioral core test battery (NCTB) and signal change on brain MRI scan were conducted (41, 42). OSHRI did not discover any Parkinsonism or severe neurologically disabled cases out of the total subjects. The proportion of workers with increased signal intensities of T1 weighted image among the Mn-exposed workers was higher than among the non-exposed. In particular, 73.5% of the welders showed increased signal intensities. Because the intensities were not correlated with neurological lesions, the study concluded that high signals of brain MRI was not necessarily Mn-induced Parkinsonism, even if the patient had recent exposure to Mn (43). However, Mn exposure was significantly correlated with neurobehavioral performance on the NCTB (44, 45). This implied that, even though the signal changes of T1 weighted image on brain MRI were not an exact index for Mn-induced Parkinsonism, it might reflect the preclinical effects such as neurobehavioral performance.

By 2008, 8 cases of Mn-induced neurological disorders had been reported, including three workers from a welding rod manufacturer (40), 4 welders (19, 31, 42) and 1 painter (46) (Table 7). The working duration of the 8 cases, aged 39 to 51 yr old, was 15 months to 15 yr. Most showed one of the major characteristics of Parkinson's syndrome. All of the welders but one had shown high signal intensity of T1 weighted image on a brain MRI. One case was not related to Mn exposure but had been exposed to organic solvents during 13 yr of working. Even though several studies had been conducted to find a relationship between Parkinsonism and organic solvents (46), the relationship between the two is still inconclusive.

The reports on the three welders (10) and the nationwide investigation by OSHRI (42) provoked more studies on welders' brain MRIs and Mn exposure (47-50). These studies found that a high percentage of high signal intensity in Mn-exposed workers, however, could not confirm a correlation between the intensity of MRI and objective neurological signs. Kang et al. (48) reported that the signal intensity of the globus pallidus on a brain MRI was a suitable single variable representing the effect of Mn accumulation in the CNS; however, it would be of limited value without the neuropathological index. In 2007, Kim et al. (51) analyzed the data from an epidemiological investigation by OSHRI using structural equation modeling; they reported that airborne Mn contributed to the pallidal index (PI) of a brain MRI and that the PI is the most effective predictor of neurobehavioral performance, after adjusting for age and level of education. These findings were confirmed by Shin et al. (52), supporting the cut-off line of the PI index value of 107.

Further evaluations of brain imaging techniques, such as ¹H magnetic resonance spectroscopy (MRS) in welders, were conducted until 2007 (53, 54). In those studies, a N-acetylaspartate/creatine ratio of MRS in the basal ganglia seems to reflect the cumulative effects of Mn exposure on the human brain. There was one case-control study on Mn and Parkinson's diseases (PD). The result of this study was not able to find a correlation between exposure to Mn and Parkinson's disease (55).

ALS is a neurodegenerative disease affecting the motor neurons of the spinal cord and brain. Although the definite etiology of ALS remains unclear, occupational or environmental exposure has been considered as one of the potential causes of ALS. In Korea, 2 cases of ALS have been reported (9, 19). A patient had been working as a spray painter at an industrial machine manufacturer for 20 yr (19) and was diagnosed with ALS. Other cases were 39-yr-old male workers from an electronic parts manufacturing company, reported to be related to lead exposure (9).