• Analytical Science and Technology
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• v.35 no.3
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• pp.93-115
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• 2022

Potential impurities in pharmaceuticals could be produced during manufacture, distribution, and storage and affect quality and safety of pharmaceuticals. In particular, highly reactive impurities could result in carcinogenic (mutagenic) effects on human body. International Conference on Harmonisation (ICH) has provided M7(R1) guideline for "Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk" and recommended an adoption of this guideline to the authorities. ICH M7(R1) guideline provides classification, accepted intakes, and controls of potential impurities in pharmaceuticals. However, since appropriate and unified analytical methods for impurities in pharmaceuticals have not been provided in this guideline, most potential impurities in pharmaceuticals are still difficult to manage and supervise by pharmaceutical companies and regulatory authorities, respectively. In this review, we briefly described definition of unintended mutagenic impurities, basic information in ICH M7(R1) guideline, and analytical methods to determine potential impurities. This review would be helpful to manage and supervise potential impurities in pharmaceuticals by pharmaceutical companies and regulatory authorities.

• Journal of Applied Biological Chemistry
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• v.57 no.1
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• pp.73-81
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• 2014

The present study was carried out to assess exposure and risk to thiophanate-methyl wettable powder for agricultural worker during mixing/loading and application with power sprayer in green pepper, cucumber and apple fields. Dermal exposure was measured with patches, gloves, socks and masks, while inhalation exposure was evaluated with personal air pump and solid sorbent. Those methods were full validated before experiment. During mixing/loading, dermal exposure amount in green pepper, cucumber and apple fields was $24.0{\pm}6.7$, $4.5{\pm}1.5$ and $18.5{\pm}0.6mg$, corresponding to mean 0.007, 0.001 and 0.005% of prepared active ingredient, respectively. The major exposed part for mixer/loader was hands (78-92%). Dermal exposure amount for applicator in green pepper, cucumber and apple fields was $84.9{\pm}14.0$, $34.0{\pm}20.8$ and $30.7{\pm}9.1mg$, corresponding to mean 0.024, 0.016 and 0.013% of applied active ingredient, respectively. The main body parts of exposure in apple field were hands, while thighs and shins in other fields. Inhalation exposure amount in green pepper, cucumber and apple fields was $1.5{\pm}2.2$, $52.7{\pm}48.9$ and $4.0{\pm}4.9{\mu}g$ during mixing/loading and $0.2{\pm}0.1$, $23.2{\pm}12.4$ and $0.4{\pm}0.6{\mu}g$ for applicator, respectively. These results were suggested that main factors affecting dermal exposure were contact frequency to the plants, foliage density, hygienic behavior, work type, and working environment, while inhalation exposure was affected mainly by working environment, especially wind. In risk assessment, margin of safety for thiophanate-methyl in all cases was over 1. However, during application in green pepper field, margin of safety was close to 1.

• The Journal of Internal Korean Medicine
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• v.30 no.1
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• pp.144-152
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• 2009

Background : Ephedra (Ephedra sinica) has been widely used to treat respiratory disease in traditional medicine of East Asia for over a hundred years. Despite safety concerns raised by some, the use of ephedra in traditional medicine is documented over more than 1,800 years. It is well established that ephedra is one of the central medicines in Korean 'Seseng constitution' medicine. In Sasang constitution medicine, all humans can be divided into one of four types: Soeumin, Soyangin, Taeumin or Taeyangin, and each constitution type has their own typical characteristics. Accordingly, it is hypothesized that the adverse effects of ephedra differ depending on the Sasang constitution classification. Objectives : The aim of this study was to determine adverse effects of ephedra which is classified as a Taeumin herb, and to observe whether the response differs or not. according to Sasang constitution classification. Methods : The study design was a double-blind randomized controlled trial. The subjects were healthy adults 20 - 50 years old who agreed to participate in this study. They were allocated through randomization to either ephedra group (N=55) or placebo group (N=24). where ephedra extract (6 g of dried ephedra) and placebo with similar opaque capsules were given twice for one day. To compare the adverse events of ephedra according to Sasang constitution classification, we analyzed blood pressure (systolic and diastolic), pulse rate, the morning questionnaire, and patient's global assessment scale score for well known adverse events: palpitation, headache, sweating, tiredness, dyspepsia, and dry mouth. Results : After ingestion of ephedra, the pulse rate had a significant increase in all constitution types. The changes of diastolic pressure in Soeumin and the changes of pulse rate in Soeumin, Soyangin and Taeumin had a significant increase in the ephedra over the control group. In the ephedra group, the palpitation and dyspepsia score of the patients' global assessment scale had a significant increase in Soeumin, with palpitation and sweating score increasing in Soyangin. Others observations were insignificant results. Conclusion : The results of this study may confirm that the physical responses or adverse effects of herbs differ for each type of Sasang constitution. Future studies using other herbs will be required to ascertain the herbal drug reaction of Sasang constitutions.

• The Korean Society of Law and Medicine
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• v.23 no.2
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• pp.119-139
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• 2022

Brain stimulation technology that administers electrical and magnetic stimulation to a brain has shown a significant level of possibility for treating a wide range of various neurological and psychiatric disorders. Depending on its nature, the technology is defined either as invasive or non-invasive, and deep brain stimulation (DBS) is one of the most well-known invasive brain stimulation technologies. Currently categorized as grade 4 medical device in accordance with Guideline On Medical Devices And Their Grades, a Notification of Ministry of Food and Drug Safety (MFDS), the DBS has been used as a stable treatment for several diseases. At the same time, the DBS technology has recently achieved substantial advancement, encouraging active discussions for its use from various perspectives. On the contrary, debates over legal regulation related to the use of DBS has relatively been smaller in numbers. In this context, this article aims to 1) introduce the DBS technology and its safety in setting out the tone; 2) touch upon major legal issues that would potentially rise from its use for four different purposes of treatment, clinical study, areas of non-standard treatment where no other methods are available, and enhancement; and finally 3) highlight disputes concerning common emerging issues observed in the aforementioned four purposes from the viewpoint of legal responsibility and liability of using the DBS, which are benefit-risk assessment, physicians' duty of information, patients' capacity to consent, control for device, and insurance coverage.

• The Journal of KAIRB
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• v.4 no.2
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• pp.36-41
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• 2022

Purpose: The purpose of this study is to evaluate how university hospital Institutional Review Boards (IRBs) in Korea classify risk when reviewing clinical trial protocols. Methods: IRB experts (IRB chairman, vice chairman, IRB administrator) in the university hospitals obtaining a Human research protection program (HRPP) or IRB accreditation in Korea were asked to fill out the Google Survey from September 1, 2020 to October 10, 2020. Result: Among the 23 responder hospitals, 8 were accredited by the American Association for Human Research Protection Program (AAHRPP) and 8 were accredited by the HRPP of Ministry of Food and Drug Safety (MFDS). Seven were accredited by Forum for Ethical Review Committees in Asia and the Western Pacific or Korea National Institution for Bioethics Policy. Thirteen of 23 hospitals (56.5%) had 4 levels (less than minimal, low, moderate, high risk), 4 hospitals had 3 levels (less than, slightly over, over than minimal risk), 1 hospital had 5 levels (4 levels plus required data safety monitoring board), and 1 hospital had 2 levels (less than, over than minimal risk) risk classification system. Thirteen of 23 hospitals (56.5%) had difficulty classifying the risk levels of research protocols. Fourteen hospitals (60.9%) responded that different standards among hospitals for risk level determination associated with clinical trials will affect the subject protection. Six hospitals (26.1%) responded that it will not. Three hospitals (13.0%) responded that it will affect the beginning of the clinical trial. To resolve differences in standards between hospitals, 14 hospitals (60.9%) responded that either the Korean Association of IRB or MFDS needs to provide a guideline for risk level determination in clinical trials: 5 hospitals (21.7%) responded education for IRB members and researchers is needed; 3 hospitals (13.0%) responded that difference among institutions needs to be acknowledged; and 1 hospital (4.3%) responded that there needs to be communication among IRB, investigator, and sponsor. Conclusion: After conducting a nationwide survey on how IRB in university hospital determines risk during review of clinical trials, it is reasonable to use 4-level risk classification (less than minimal, low, moderate, high risk); the most utilized method among hospitals. Moreover, personal information and conflict of interest associated with clinical trials have to be considered when reviewing clinical trial protocols.

• Journal of Industrial Convergence
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• v.21 no.6
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• pp.37-42
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• 2023

This study aimed to examine the safety of HemoHIM, a dietary supplement containing methoxsalen. HemoHIM is a dietary supplement marketed globally, and a competitor to ginseng. It has been reported to contain methoxsalen, a plant extract for treating psoriasis and vitiligo. Methoxsalen is known to cause hepatotoxicity, but most of the cases has been reported from ingestion as a drug, not a food. There are no reports of hepatotoxicity from the consumption derived from natural products such as Angelica gigas, Cnidium officinale, and Paeonia lactiflora, which are the main ingredients in the HemoHIM. However, a recent case of acute hepatitis was reported in Hong-Kong after ingestion of HemoHIM. It is difficult to conclude that hepatitis was caused by HemoHIM, because there was no check of co-occurring medications with a higher risk of hepatotoxicity, no description of the progress, no quantitative comparison of methoxsalen in HemoHIM to it in common foods such as carrots and celery, and no description of the patient's underlying diseases. On the other hand, there was a study that suggest hemoHIM is safe, and that study had adequate number of subjects even though more studies are needed to ensure safety.

• Journal of Food Hygiene and Safety
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• v.31 no.4
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• pp.227-249
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• 2016

Arsenic and its compounds vary in their toxicity according to the chemical forms. Inorganic arsenic is more toxic and known as carcinogen. The provisional tolerable weekly intake (PTWI) of $15{\mu}g/kg$ b.w./week established by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) has been withdrawn, while the EFSA panel suggested $BMDL_{0.1}$ $0.3{\sim}8{\mu}g/kg\;b.w./day$ for cancers of the lung, skin and bladder, as well as skin lesions. Rice, seaweed and beverages are known as food being rich in inorganic arsenic. As(III) is the major form of inorganic arsenic in rice and anaerobic paddy soils, while most of inorganic arsenic in seaweed is present as As(V). The inorganic arsenic in food was extracted with solvent such as distilled water, methanol, nitric acid and so on in heat-assisted condition or at room temperature. Arsenic speciation analysis was based on ion-exchange chromatography and high-performance liquid chromatography equipped with atomic absorption spectrometry and inductively coupled plasma mass spectrometry. However, there has been no harmonized and standardized method for inorganic arsenic analysis internationally. The inorganic arsenic exposure from food has been estimated to range of $0.13{\sim}0.7{\mu}g/kg$ bw/day for European, American and Australian, and $0.22{\sim}5{\mu}g/kg$ bw/day for Asian. The maximum level (ML) for inorganic arsenic in food has established by EU, China, Australia and New Zealand, but are under review in Korea. Until now, several studies have conducted for reduction of inorganic arsenic in food. Inorganic arsenic levels in rice and seaweed were reduced by more polishing and washing, boiling and washing, respectively. Further research for international harmonization of analytical method, monitoring and risk assessment will be needed to strengthen safety management of inorganic arsenic of foods in Korea.

• Korean Journal of Occupational Health Nursing
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• v.9 no.1
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• pp.5-17
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• 2000

The occupational health nursing guideline for primary care was developed by the Korean Academic Society of occupational health nursing and the organization for occupational health nurses (currently known as the Korean Association of Occupational Health Nurses) in 1993. Since then, there have been many changes in the health care environment and job performance of occupational health nurses. Appropriate revisions are necessary of the guidelinea based on this background. The purpose of this study was to describe the use of the occupational health nursing guideline for primary care and to analyze the characteristics of primary care activities by occupational health nurses. The questionnaire was mailed to 150 occupational health nurses(OHNs) with the response rate of 64%. The results can be summarized as follows; 1. 65.6% of OHNs have been using the guideline for primary care and 75.9% of them agreed that the guideline was be helpful for their job. 2. Common symptom care, emergency care and chronic illness care were more frequently implemented than occupational disease care by OHNs. In manufacturing industries, emergency care was more frequently implemented than chronic illness care in contrast to the service industries. 3. Most frequent common symptoms treated by OHNs were indigestion, diarrhea, abdominal pain, headache, and coughing. In the case of chronic illness, OHNs more frequently treated diseases of the gastro-intestinal system, skin and sensory organs, and the respiratory system. Emergency care for bruises, burn, and abrasions was more frequently provided. VDT syndrome was the most common occupational disease cared by OHNs in manufacturing and service industries. 4. OHNs prescribed the medicine for external application more frequently than internal medicine. Remedy for colds, analgesics, vitamins, and digestives were more frequently used. From these results, we suggest that the guideline should be revised to emphasize the activities consisting problem finding such as health assessment, physical examinations, monitoring and screening, and to renew the drug list in the range of over- the counter medication (OTC). In the future, the guideline will include the strategies for the role as the case manager.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.30 no.2
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• pp.143-149
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• 2004

Background: Some clinical trials have reported that a new analgesic combination of tramadol and acetaminophen provides good efficacy in various pain models. For the more clinical uses of this agent, comparisons about the onset of analgesia and analgesic efficacy in the acute state of pain with the other drugs known as strong analgesics were needed. Purpose: The goal of this study was to compare the times to onset of analgesia and the other analgesic efficacy of 75 mg tramadol/650 mg acetaminophen and 20 mg codeine/500 mg acetaminophen/400 mg ibuprofen in the treatment of acute pain after oral surgery. Patients and Methods: Using a randomized, single-dose, parallel-group, single-center, and active-controlled test design, this clinical study compared the times to onset of analgesia using a two-stopwatch technique and the other analgesic efficacy of the single-dose tramadol/acetaminophen and codeine/acetaminophen/ibuprofen. These were assessed in 128 healthy subjects with pain from oral surgical procedures involving extraction of one or more impacted third molars requiring bone removal. From the time of pain development, the times to onset of perceptible and meaningful pain relief, pain intensity, pain relief, an overall assessment, and adverse events of the study medications were recorded for 6 hours. Results: The demographic distribution and baseline pain data in the two groups were statistically similar. The median times to onset of perceptible pain relief were 21.0 and 24.4 minutes in the tramadol/acetaminophen and codeine/acetaminophen/ibuprofen groups respectively and those to onset of meaningful pain relief were 56.4 and 57.3 minutes, which were statistically similar. The other efficacy variables such as mean total pain relief (TOTPAR) and the sum of pain intensity differences (SPID) were also similar in the early period after pain development and drug dosing. The safety of tramadol/acetaminophen was well tolerated and very comparable to that of codeine/acetaminophen/ibuprofen. Conclusions: In this acute dental pain model, the onset of analgesia and analgesic efficacy of tramadol/acetaminophen was comparable to that of codeine/acetaminophen/ibuprofen. These results showed that tramadol/acetaminophen was recommendable for fast and effective treatment in the management of postoperative acute pain.

• Journal of Korean Medicine Rehabilitation
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• v.25 no.3
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• pp.1-9
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• 2015

Objectives To evaluate Shinbaro Pharmacopuncture safety through analysis of potential single-dose intramuscular toxicity of Sinbaro Pharmacopucture in SD rats and Beagle dogs. Methods Single-dose intramuscular toxicity of Shinbaro Pharmacopuncture was assessed in accordance with Korea Food and Drug Administration Guidelines for toxicity testing of Medicinal Products. The SD rats were treated intramuscularly with Shinbaro Pharmacopuncture at doses of 0, 4.6, 9.2, and 18.5 mg/kg, respectively. The Beagle dogs were treated intramuscularly with Shinbaro Pharmacopuncture at doses of 2.3, and 4.6 mg/kg, respectively, and after 3 days, the procedure was repeated a second time at doses of 0.6, and 1.2 mg/kg, respectively, for toxicity testing. Mortality, change in body weight, and necropsy findings were examined for the study period. Results There were no mortalities, general symptoms, or body weight changes in the SD rats. While pyelectasis of the left kidney was observed in a male rat in the 4.6 mg/kg administration group, natural occurrence is common, and does not appear to be related with the test substance. No mortalities were observed in the Beagle dogs. In assessment of general symptoms, a female dog in the 9.2 mg/kg group displayed body weight decrease due to leftover food, but the change in body weight was within the normal range seen at 6~7 months, and the necropsy findings were not significant. The toxicity of the test substance appears to be minimal. Conclusions The results suggest that the lethal dose 50 ($LD_{50}$) and approximate lethaldose (ALD) value in single intramuscular administration of Shinbaro Pharmacopuncture in SD rats and Beagle dogs are higher than 18.5 mg/kg.