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Case Report
Glioblastoma in a paper industry worker exposed to high concentrations of formaldehyde: a case report
Youngshin Lee, Jiwoon Kwon, Miyeon Jang, Seongwon Ma, Kyo Yeon Jun, Minjoo Yoon, Shinhee Ye
Ann Occup Environ Med 2024;36:e17.   Published online July 5, 2024
DOI: https://doi.org/10.35371/aoem.2024.36.e17
AbstractAbstract AbstractAbstract in Korean PDFSupplementary MaterialPubReaderePub
Background

Formaldehyde was classified as a Group I Carcinogen by the International Agency for Research on Cancer (IARC) in 2006. While the IARC has stated that there is a lack of evidence that formaldehyde causes brain cancer, three meta-analyses have consistently reported a significantly higher risk of brain cancer in workers exposed to high levels of formaldehyde. Therefore, we report a case of a worker who was diagnosed with glioblastoma after being exposed to high concentrations of formaldehyde while working with formaldehyde resin in the paper industry.

Case presentation

A 40-year-old male patient joined an impregnated paper manufacturer and performed impregnation work using formaldehyde resin for 10 years and 2 months. In 2017, the patient experienced a severe headache and visited the hospital for brain magnetic resonance imaging, which revealed a mass. In the same year, the patient underwent a craniotomy for brain tumor resection and was diagnosed with glioblastoma of the temporal lobe. In 2019, a craniotomy was performed owing to the recurrence of the brain tumor, but he died in 2020. An exposure assessment of the work environment determined that the patient was exposed to formaldehyde above the exposure threshold of 0.3 ppm continuously for more than 10 years and that he had high respiratory and dermal exposure through performing work without wearing a respirator or protective gloves.

Conclusions

This case report represents the first instance where the epidemiological investigation and evaluation committee of the Occupational Safety and Health Research Institute in Korea recognized the scientific evidence of work-related brain tumors due to long-term exposure to high concentrations of formaldehyde during impregnated paperwork. This case highlights the importance of proper workplace management, informing workers that prolonged exposure to formaldehyde in impregnation work can cause brain tumors and minimizing exposure in similar processes.

고농도 포름알데히드에 노출된 제지 산업 근로자에서 발생한 교모세포종: 사례보고
배경
포름알데히드는 2006년 국제암연구소(IARC)에서 1군 발암 물질로 분류되었다. IARC는 포름알데히드가 뇌종양을 유발한다는 증거가 부족하다고 밝혔지만, 세 건의 메타 분석에서 고농도의 포름알데히드에 노출된 근로자의 뇌종양 위험도가 상당히 높다고 일관되게 보고했다. 이에 포름알데히드 수지를 사용하는 제지 산업에서 근무하던 중 고농도의 포름알데히드에 노출되어 교모세포종 진단을 받은 근로자의 사례를 보고하고자 한다.
증례
40세 남성 환자는 함침지 제조업체에 입사하여 10년 2개월 동안 포름알데히드 수지를 사용한 함침 작업을 수행했다. 2017년 9월, 환자는 심한 두통을 느껴 병원을 방문하여 촬영한 뇌 자기공명영상(MRI)의 결과에서 종양이 발견되었다. 같은 해에 환자는 뇌종양 절제를 위해 개두술을 시행하였고 측두엽의 교모세포종을 진단받았다. 2019년 뇌종양 재발로 개두술을 시행하였지만 치료에도 불구하고 2020년 사망하였다. 환자의 작업환경 노출 평가 결과, 10년 이상 지속적으로 노출 기준치인 0.3ppm 이상의 포름알데히드에 노출되었고, 호흡기나 보호 장갑을 착용하지 않고 작업을 수행해 호흡기 및 피부 노출이 높았던 것으로 확인되었다.
고찰
본 사례는 국내 산업안전보건연구원 역학조사평가위원회가 함침 작업 중 고농도 포름알데히드에 장기간 노출되어 업무상 뇌종양이 발생하였다는 과학적 근거를 인정한 첫 사례이다. 이 사례를 통해 함침 작업에서 포름알데히드에 장기간 노출되면 뇌종양이 발생할 수 있음을 근로자에게 알리고 유사한 공정에서 노출을 최소화하는 등 적절한 작업환경관리의 필요성을 강조한다.
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Original Article
The Brain Pathology on Recovery of Brain MRI after Manganese Administration in Rats
Ji Hyeon Jung, Jung Il Kim, Se Young Kim, Min Ho Jung, Soon Sub Choi, Soo Jin Kim, Young Jin Park, Kap Yeol Jung
Korean Journal of Occupational and Environmental Medicine 2010;22(4):371-377.   Published online December 31, 2010
DOI: https://doi.org/10.35371/kjoem.2010.22.4.371
AbstractAbstract PDF
OBJECTIVES
This study was carried out to investigate the effect on manganese on the brain of Sprague-Dawley rats, with particular focus on changes to anatomical pathology when brain MRI was recovered after manganese administration.
METHODS
There were 15 rats divided into 3 groups of 5 based on dose of manganese: control group, low dose group (10 mg/kg), and high dose group (40 mg/kg). Each dosing group received an injection of normal saline and manganese via the tail vein once a week for 4 weeks. And then, the rats were observed for 12 weeks after stopping manganese administration. Next, each rat underwent a brain MRI and then each was sacrificed. After the rats were killed, the concentrations of blood manganese were measured, and pathologic examinations of the brain were performed.
RESULTS
The signal intensity of basal ganglia on T1-weighted imaging of brain MRI did not differ between dosing groups. However, the ratio of neuron/glial cell in the basal ganglia was decreased in the low- and high-dose groups compared to the control group.
CONCLUSIONS
This study showed that the damage of neuron in basal ganglia might be permanent after signal intensity of basal ganglia on T1-weighted imaging of brain MRI was recovered.

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Original Article
The Change of Brain MRI and Pathology According to the Administered Dose of Manganese in Rats
Jae Myeong Lee, Jung Il Kim, Yoon Kou Kim, Min Ho Jung, Soon Sub Choi, Dae Chul Kim, Kap Yeol Jung
Korean Journal of Occupational and Environmental Medicine 2009;21(2):184-191.   Published online June 30, 2009
DOI: https://doi.org/10.35371/kjoem.2009.21.2.184
AbstractAbstract PDF
OBJECTIVES
This study was carried out to investigate the effect of manganese on the brains of rats, and chronic exposure to manganese is known to induce Parkinsonism in human.
METHODS
The rats were divided into three groups: the first group was a control group that was administrated normal saline, and the second group was subdivided into the low dose group (10 mg/kg) and the high dose group (40 mg/kg) according to the administered dose of manganese. The rats of each group received an injection of normal saline and manganese via a tail vein once a week for 4 weeks. The rats were sacraficed at 4 weeks after the first adminstration of manganese. Brain MR imaging was performed before the rats were killed. After the rats were killed, the concentration of blood manganese was measured, and pathologic examination of the brain was performed in all the groups.
RESULTS
The concentration of blood manganese was increased proportionally to the administered dose. The signal intensity of the basal ganglia on the T1-weighted imaging of brain MRI was increased in accordance with the administered dose. The ratio of neuron/glial cells in the basal ganglia was decreased in the experiment group as compared to that of the control group.
CONCLUSIONS
This study showed that the signal intensity and the damage of neurons in basal ganglia were increased according to the administered dose of manganese in rats.

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Original Article
Cerebrovascular, and Other Health Effects, Due to the Exposure of Ex-Workers to Carbon Disulfide in the Maunfacture of Rayon
Joo Ja Kim, Kyung Jae Lee, Hyun Sook Hong, Dae Ho Kim
Korean Journal of Occupational and Environmental Medicine 2003;15(1):72-83.   Published online March 31, 2003
DOI: https://doi.org/10.35371/kjoem.2003.15.1.72
AbstractAbstract PDF
OBJECTIVE: The purpose of this study was to evaluate the cerebrovascular and other related health effcets, due to the exposure of ex-workers to carbon disulfide in the manufacture of rayon.
METHODS
The study subjects comprised of 453 workers from the rayon manufacturing industry (387 males, 66 females). They were examined with a brain MRI and for other risk factors related to their occupation, such as age, work department, work duration, duration of work cessation, and blood pressure. Laboratory tests were also performed such as blood sugar, hemoglobin, cholesterol, etc. The cumulative exposure levels were calculated as the mean exposure level, per work department, multiplied by the total work duration in months.
RESULTS
75.1% of the subjects were between the ages of 40 and 59 years. 76.0% of the subjects had worked in high exposure departments (e.g., department of spinning and refining etc). 52.5% of the subjects had worked for more than 10 years, and 63.3% of the subjects had ginven up the work (exposure) more than 10 years earlier. The brain MRI findings were normal, a single lacunar infarct, multiple lacunar infarcts (mostly, on subcortex and white matter), and a hemorrhage in 52.5, 8.6, 36.2 and 2.7% respectively. Multiple lacunar infarcts were not related to the cumulative exposure level but in the female workers only, were significantly related to the increasing level of work duration (p<0.05), and in the male workers only, were related to the increased duration of work cessation and age (p<0.01). Abnormal rates of laboratory tests were higher in the multiple lacunar infarcts subjects with hypertension compared to theose with normal brain MRI findings (p<0.01).
CONCLUSIONS
The multiple lacunar infarcts of the brain seemed not to be related to the cumulative exposure level but to the low exposure departments, duration of work, duration of work cessation, age and hypertension. This was conducted as a health evaluation on workers from the rayon manufacturing industry who had terminated their exposure to carbon disulfide many years earlier.

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Original Article
Cancer Incidence in the Vicinity of Korean AM Radio Broadcast Towers
Hyoung June Im, Mi Na Ha, Soo Hun Cho
Korean Journal of Occupational and Environmental Medicine 2001;13(3):296-305.   Published online September 30, 2001
DOI: https://doi.org/10.35371/kjoem.2001.13.3.296
AbstractAbstract PDF
OBJECTIVES
Several studies have raised the possibility that exposure to electrical and/or magnetic fields may be particularly harmful in the promotion or initiation of cancer. The purpose of this study which was based on a geographical correlation design was to investigate any association that may exist between residing near radio broadcast towers and carcinogenic activity in Korea.
METHODS
In this study, the health effects of EMF of 10 AM radio broadcast towers in Korea were investigated. The electric powers of the towers were above 100kW. We chose exposed areas that were located within 2 km from the towers as well as four control regions which had similar populations in the same province(Do) but had no towers nearby. The incidence of leukemia, malignant lymphoma, brain tumor and breast cancer between the exposed areas and the control areas was compared. The standardized incidence ratios(SIRs) were calculated. Korean Medical Insurance data(between Nov,1,1993 and Oct,31,1996) was used for the cancer incidence estimation. The Nationwide Population Census data(in 1995) and the Resident Register data(in 1995) were used for information about population and locations.
RESULTS
Among the 10 exposed areas, one area for leukemia and one area for brain tumor showed a significantly high incidence compared to the control areas. There were no significant increased areas for malignant lymphoma and breast cancer.
CONCLUSIONS
This study design must be considered to be exploratory and not used for determining causality. However, the results suggest the necessity for further analytical epidemiological studies that have a more precise exposure measurement scale and information on confounding factors.

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Original Article
An Association between Brain MRI and Neurologic Findings in Welders Exposed to Manganese Fume
Hyeon Woo Yim, Ji Hong Kim, Young Gyu Phee, Jung Wan Koo, Kang Sook Lee, Chung Yill Park, Jeong Wook Lee, Si Ryung Han, Hye Suk Jang
Korean Journal of Occupational and Environmental Medicine 1998;10(2):161-171.   Published online May 31, 1998
DOI: https://doi.org/10.35371/kjoem.1998.10.2.161
AbstractAbstract PDF
This study was carried out to investigate the relationship between brain magnetic resonance imaging (MRI) and neurological findings in welders exposed to manganese fume. Thirty five welders from a bus manufacturing factory who were occupationally exposed to low dose manganese fume were examined. We collected the information on the demo graphic factors and welding careers. Laboratory investigations included blood and urine manganese concentration and blood chemistry. Brain MRI was checked, and high signal intensity of the globus pallidus was graded from 0 to 3 compared to the white matter of the frontal lobe. Neurologic examination wart carried out. The results were as follows ; 1. The mean age of workers was 48.3+/-5.7 years, mean duration of welding was 21.4 +/-5.6 Years. 2. On brain MRI, high signal intensity in the globes pallidus was observed in 27 workers (77.1%) Among them, 18 cases (66.7%) showed remarkably high signal intensity (grade 2) Mean concentration of blood manganese was higher in those with high signal intensity and correlated to the grade of high signal intensity (p=0.02) 3. On neurologic examination, no workers showed the finding of typical parkinsonism. But 11 workers (31.4%) showed subtle neurological abnormalities such as gait without associated arm movement, postural instability, intention tremor, and so on. Blood manganese concentration of neurologically abnormal group was 2.4+/-0.7 microgram/dL, which was significantly higher, compared to 1.8+/-0.7 microgram/dL of neurologically normal group (p=0.03). 4. Among 27 workers who showed high signal intensity on brain MRI, 10 workers (37%) were neurologically abnormal. Higher grade of signal intensity on globus pallidus showed higher rate of neurologic abnormality (p<0.05) Especially postural instability and gait without associated arm movement were prominent findings. These bindings suggest that high signal intensity on brain MRI might be associated with a prodromal sign of manganese intoxication. Careful neurologic examination should be tool lowed up on welders showing high signal intensity in the golbus pallidus of brain MRI.

Citations

Citations to this article as recorded by  
  • Parkinson's disease in a worker exposed to insecticides at a greenhouse
    Yangwoo Kim, Inah Kim, Jung-Min Sung, Jaechul Song
    Annals of Occupational and Environmental Medicine.2021;[Epub]     CrossRef
  • Association of MRI T1 relaxation time with neuropsychological test performance in manganese- exposed welders
    R.M. Bowler, C-L. Yeh, S.W. Adams, E.J. Ward, R.E. Ma, S. Dharmadhikari, S.A. Snyder, S.E. Zauber, C.W. Wright, U. Dydak
    NeuroToxicology.2018; 64: 19.     CrossRef
  • Occupational Neurological Disorders in Korea
    Eun-A Kim, Seong-Kyu Kang
    Journal of Korean Medical Science.2010; 25(Suppl): S26.     CrossRef
  • State-of-the-Science Review: Does Manganese Exposure During Welding Pose a Neurological Risk?
    Annette B. Santamaria, Colleen A. Cushing, James M. Antonini, Brent L. Finley, Fionna S. Mowat
    Journal of Toxicology and Environmental Health, Part B.2007; 10(6): 417.     CrossRef
  • Sequelae of fume exposure in confined space welding: A neurological and neuropsychological case series
    Rosemarie M. Bowler, Sanae Nakagawa, Marija Drezgic, Harry A. Roels, Robert M. Park, Emily Diamond, Donna Mergler, Maryse Bouchard, Russell P. Bowler, William Koller
    NeuroToxicology.2007; 28(2): 298.     CrossRef
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