Current Situation of the International Recognition of Toxicologists -Update of the Japanese Society of Toxicology-

Horii, Ikuo The Korean Society of Toxicology Korea Environment 2001 Toxicological Research Vol.17 No.-

Issuance of certification and licensing for toxicologists authorized by the Japanese Society of Thxicology (JST) became effective on July 24, 1997. The certification system consists of examination, eligibility requirements for the applicants, authorization/license by the board of trustees of JST, and the re-certification of previously authorized qualification. In the last 2-3 years, about 30-40% of candidates for the examination have succeeded. The Committee has estimated that the level of the examination would be sufficient to determine qualified toxicologists. This updated status and a detailed explanation are to be presented at the workshop. In global terms, the JST special committee agrees that "harmonization of certification/registration procedure for qualified toxicologists means to ensure/set the minimum requirement for the global authorization of qualified toxicologists". The following items in global authorization are ad-dressed for further discussion: (1) What's the benefit\ulcorner (2) Toxicological safety assessment standards, and (3) the JST position for authorization.orization.

International Harmonization of Accreditation of Toxicologists

Satoh, Tetsuo The Korean Society of Toxicology Korea Environment 2001 Toxicological Research Vol.17 No.-

In the past, IUTOX engaged in dialogue with various international toxicology organizations to address this important issue. IUTOX Executive Committee engaged in activities that support accreditation and/or registration of toxicologists around the world. As a result of discussions held during the IUTOX-sponsored workshop at the 2000 Annual Meeting of the SOT in Philadelphia, it was decided to create an international forum, the "International Assembly for the Recognition of Toxicologists"(IART). The mission of IART was defined as threefold: 1) to establish a forum for development of criteria for recognizing qualified experts in toxicology; 2) to assist "recognizing organizations" in establishing these criteria; and 3) to promote identification and training needs to enhance expertise in toxicology. The membership of IART is open to all organizations (e.g., registries, boards, academies, etc.) whose purpose is the recognition of expertise in toxicology.rtise in toxicology.

Future of Toxicology and Role of Asian Chemical Safety Network

Kaminuma, Tsuguchika The Korean Society of Toxicology Korea Environment 2001 Toxicological Research Vol.17 No.-

Toxicology is under challenge from several new trends in science and technology, namely computer, the Internet, genome projects, genomic technologies, and combinatorial chemistry. These new trends will drastically change research style of toxicology. In addition to conventional uni cellular tests and animal tests using rodents, computer simulation, DNA chips (microarrays), in vivo tests using simple model organisms such as nematodesor flies become important routine screening tests. How to arrange these tests in tiers will become a new problem. Endocrine disruptors hypothesis is a good example for this kind of futuristic approach. Computer, particularly the Internet, is also enabling toxicologists and regulatory experts to collaborate more closely. The IPCS (International Program for Chemical Safety) which is ajoint project of WHO, ILO and UNEP, is a well-known international collaborative research for chemical risk assessments. The GINC project of IPCS is an effort to utilize the Internet for such collaborations. Some efforts were also made to establish regional collaboration network in East Asia under this project.

Free Radical Toxicology and Cancer Chemoprevention

Lin, Jen-Kun The Korean Society of Toxicology Korea Environment 2001 Toxicological Research Vol.17 No.-

Most reactive oxygen species (ROS) are free radicals and implicated in the development of a number of disease processes including artherosclerosis, neurodegenerative disorders, aging and cancer. ROS are byproducts of a number of in vivo metabolic processes and are formed deliberately as part of nor-mal inflammatory response. On the other hand, ROS are generated either as by products of oxygen reduction during xenobiotic metabolism or are liberated as the result of the futile redox cycling of the chemical agents including several chemical carcinogens. A better understanding of the mechanisms of free radical toxicity may yield valuable clue to risks associated with chemical exposures that leading to the development of chronic diseases including cancer. The molecular biology of ROS-mediated alterations in gene expression, signal transduction and carcinognesis is one of the important subjects in free radical toxicology. Epidemiological studies suggest that high intake of vegetables and fruits are associated with the low incidence of human cancer. Many phytopolyphenols such as tea polyphenols, curcumin, resveratrol, apigenin, genistein and other flavonoids have been shown to be cancer chemopreventive agents. Most of these compounds are strong antioxidant and ROS scavengers in vitro and effective inducers of antioxidant enzymes such as superoxide dismutatse, catalase and glutathione peroxidase in vivo. Several cellular transducers namely receptor tyrosine kinase, protein kinase C, MAPK, PI3K, c-jun, c-fos, c-myc, NFkB, IkB kinase, iNOS, COX-2, Bcl-2, Bax, etc have been shown to be actively modulated by phyto-polyphenols. Recent development in free radical toxicology have provided strong basis for understanding the action mechanisms of cancer chemoprevention.

An Approach to Detect Health Risk of Dioxins

Pavittranon, Sumol,Sinhaseni, Palarp The Korean Society of Toxicology Korea Environment 2001 Toxicological Research Vol.17 No.-

March 19, 1999, the renovation qf the runway of the Bo-Fai ai1field in Hua Hin, Prachubk-erikhan, Thailand, unearthed chemicals which were left over from the project "anch Hand Operation" held during the Vietnam war era. The chemical mixtures were analyzed by the US EPA, the Department oj Medical Sciences (DMSc), Ministry oj Public Health (MoPH) and the Pollution Control Department (PCD), the Ministry oj Science Technology and Environment (MOSTE) of Thailand, The samples were found to contain several defoliants used in the operation. They were 2,4-D, 2,4,5-T, Dicamba, Cocydelic acid, and Dioxins. Due to the complexity of the issue, the multiplicity of possible health effects, and the socio-economic implications for imports and exports, the Thai Society of Toxicology submitted a proposal to request World Health Organization (WHO), Geneva. The assistance is for the area of chemical safety and called for immediate action to explore the magnitude qf risk involved with Dioxins. In this paper we present our approach to health risk assessment which takes into an account the epidemiological studies of high-risk group exposed to the Ranch Hand operation. Dioxins are endocrine disruption chemicals which public concerns are developed due to presumption that a hazard exists (www.eva.gov/dioxins/html) for which current methodologies are deemed insufficient. The recent concepts of how oxidative stress toxicants may affect health end points and biomarkers of exposure of exposed individuals are discussed. While research activities are undergoing, The Thai Society of Toxicology do not anticipate significant risk to local residents and the environment due to our concurrence with opinion from the international experts invited by the World Health Organization proposed to the local experts at a workshop in Bangkok.n Bangkok.

CYTOTOXICITY OF D-GALACTOSAMINE ON PRIMARY CULTURES OF ADULT RAT HEPATOCYTES

Yang, K.H.,Park, Kwan-Ha,Kim, Byung-Sam The Korean Society of Toxicology Korea Environment 1987 Toxicological Research Vol.3 No.2

Primary cultures of adult rat hepatocytes were used to study the cytotoxicity of D-galactosamine. Hepatocytes were isolated by a collagenase perfusion technique and maintained as monolayers in serum-free medium on collagen-coated culture dishes. Treatment of galactosamine to the culture markedly inhibited the uptake of ${\alpha}$-aminoisobutyric acid (AIB) inducible with glucagon and dexamethasone. At0.1 mM of galactosamine, AIB uptake was inhibited significantly when treated for 12 hr. At higher doses (0.25, 0.5 and 1.0mM), a significant inhibition was noticed after 1 hr exposure. Generally the magnitude of the inhibition was related to the dose and treatment time of galactosamine. Treatment of galactosamine also produced a dose- and treatment time-related suppression of the tyrosine aminotransferase (TAT) induction caused by dexamethasone. Meanwhile, uptake of ouabain was not affected by the treatment of galactosamine. The viability of the hepatocytes was decreased only slightly by the treatment of galactosamine; more than 87% of the cells excluded tryphane blue when treated 1 mM galactosamine for 12 hr. Galactosamine induced depressions of AIB uptake and TAT activity were prevented by the simultaneous addition of uridine to the culture. D-Galactosamine, cytotoxicity, hepatocytes culture, ${\alpha}$-aminoisobutyric acid uptake, tyrosine aminotransferase.

Effect of Smoking on Theophylline Pharmacokinetics in Normal Korean Volunteers

Park, Kyoung-Ho,Shin, Hyun-Teak,Kim, Nak-Doo The Korean Society of Toxicology Korea Environment 1988 Toxicological Research Vol.4 No.1

In order to evaluate the effect of cigarette smoking on the pharmacokinetics of theophylline in Koreans, doses of 4.5 to 5.0 mg/kg of theophylline, as injectable aminophylline, were administered to 12 normal young volunteers (male, 22 to 35 yrs;mean, 26 yrs) through intravenous infusion over 30 minutes, and pharmacokinetics of theophylline were tested. Among subjects, six were nonsmokers and the other were smokers (range 1 to 2 packs/day). Also the correlations between plasma and saliva theophylline concentrations were investigated by determining the concentrations of theophylline in saliva simultaneously at each plasma sampling time. The total body clearances of theophylline in smokers (Mean${\pm}$SD, 0.0578${\pm}$0.0092 L/hr/kg)were appreciably higher than thoxe of nonsmokers (Mean${\pm}$SD, 0.0359${\pm}$0.0063 L/hr/kg), and the half-lives of theophylline in smokers averaged 5.36${\pm}$1.22hr, and significantly shorter than those of nonsmokers which averaged 9.14${\pm}$1.73hrs(p<0.005). But the apparent volumes of distribution of theophylline did not show any significant difference between smokers (Mean${\pm}$SD,0.44 ${\pm}$0.05L/kg) and nonsmokers (Mean${\pm}$SD, 0.46${\pm}$0.05L/kg). The average concentration ratios in saliva and plasma were 0.61 in smokers and 0.56 in nonsmokers after 2 hrs following drug administrations, and the smoker group had a slightly higher value of ratio(S/P) than the nonsmoker group (p<0.05). The correlations between saliva and plasma theophylline concentration in smokers were r=0.852(p<0.0005) within 2 hr and r=0.985(p<0.0005) after 2 hrs and also those of nonsmokers were r=0.729(p<0.0005) within 2 hrs and r=0.957(p<0.0005) after 2 hrs starting the infusion. From the results, it was found that smoking cigarettes had significantly increased the clearance of theophylline and that the relationships between saliva and plasma theophylline concentrations in all subjects were better after 2 hrs than within 2 hrs starting the infusion of aminophlline.

A POSSIBLE MECHANISM OF POLYACETYLENE: MEMBRANE CYTOTOXICITY

Kim, Hyeyoung,Lee, You-Hni,Kim, Shin-Il The Korean Society of Toxicology Korea Environment 1988 Toxicological Research Vol.4 No.2

The effects of polyacetylenes on living membrances, rat erythrocyte and murine leukemic L1210 cell as well as artificial lipid bilayer were determined to investigate the cytotoxic mechanism of polyacetylenes against cancer cell lines. As results, panaxydol and panaxynol caused erythrocyte hemolysis dose-dependently while panaxytriol had no lysis. For liposomes composed of phosphatidyl choline (PC) and phosphatidic acid(PA), all three polyacetylenes supressed the osmotic behavior at the same degree.

INHIBITORY EFFECTS OF RED GINSENG EXTRACT ON PRENEOPLASTIC NODULE FORMATION IN THE RAT LIVER OBSERVED BY RAPID BIOASSAY OF CARCINOGENESIS

Kim, Yun-Bae,Lee, Yong-Soon The Korean Society of Toxicology Korea Environment 1988 Toxicological Research Vol.4 No.2

This study was carried out to investigate the inhibitory effects of red ginseng extract on preneoplastic nodule formation in the rat liver using a rapid bioassay of hepatocarcinogenesis. Wistar male rats in test groups were fed diets containing 3.0, 0.3 or 003% of red genseng extract for 6 weeks after 2 week of dosing with diethylnitrosamine (DEAN, 200 mg/kg B.W., I.P.) or saline solution. The rats in the control groups were treated with DENA or saline alone. Three weeks after the beginning of the experiment, the two-thirds partial hepatectomy was performed on all animals. The inhibitory effects were investigated by measuring the number, total area and size of hyperplastic nodules enhanced by the 2/3 partial hepatectomy following induction with DENA. The results obtained were summarized as follows: 1. In general, the body weight gains of the rats fed diets containing red ginseng extract were higher than those of other groups.

PROTECTIVE EFFECT OF SCOPARONE AGAINST ACETAMINOPHEN INDUCED LIVER TOXICITY IN MICE

Huh, Keun,Park, Jong-Min,Chung, Jung-Rok The Korean Society of Toxicology Korea Environment 1987 Toxicological Research Vol.3 No.2

Protective effect of scoparone against the acetaminophen inducible hepatic toxicity in mice was investigated. Scoparone (5mg/kg) was administered intraperitoneally to mice daily for 5 days. Scoparone pretreatment before the administration of acetaminophen has blocked subsequent increases in liver to body weight ratio. When biological changes were measured, scoparone protects against acetaminophen inducible hepatotoxicity in mice as evidenced by the decreased formation of lipid peroxide, lowered serum transaminase activity and the decreased level of serum acetaminophen. In conjuction with the results of Huh (Arch. Pharm. Res. 10, 165(1987)), these results suggest that the most likely mechanism for the observed protective effects of scoparone against the acetaminophen-induced hepatotoxicity is the induction of hepatic microsomal UDP-glucuronyltransferase activity.