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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
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Journal DOI :
The Korean Society of Toxicology
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Volume & Issues
Volume 18, Issue 4 - Dec 2002
Volume 18, Issue 3 - Sep 2002
Volume 18, Issue 2 - Jun 2002
Volume 18, Issue 1 - Mar 2002
Selecting the target year
Safety and Risk Assessment of 3-Monochloro-1,2-propanediol (3-MCPD)
Toxicological Research, volume 18, issue 1, 2002, Pages 1~11
3-Monochloro-1,2-propanediol(3-MCPD) is currently being a matter of concern because of its toxicity. 3-MCPD produced during the acid hydrolysis of soybean products has been reported to be mutagenic, neurotoxic, nephrotoxic and spermatotoxic. Howerer, the carcinogenicity of 3-MCPD is a controversial issue over the past several decades. 3-MCPD characteristically showed a variety of toxicities in reproductive system such as, decrease in sperm number and sperm motility, infertility, loss of sperm function, and weight decrease in ovary. Due to the toxicity of 3-MCPD, exposure to 3-MCPD has been proposed to be reduced to as low a level as technologically feasible. 3-MCPD can be detected in soy sauce or non-soy sauce products. The legal limit for 3-MCPD this year has been suggested to be 20 ppb（
/kg）in the European Community. In Korea, the permissible level of 3-MCPD is expected to be 0.3 ppm. In this study, 3-MCPD was toxicologically evaluated in terms of risk assessment in humans.
Initial Risk Assessment of Acetanilide in OECD High Production Volume Chemical Program
Park, Hye-Youn ; Park, Yoonho ; Sanghwan Song ; Kwon, Min-Jeoung ; Koo, Hyun-Ju ; Jeon, Seong-Hwan ; Na, Jin-Gyun ; Park, Kwangsik ;
Toxicological Research, volume 18, issue 1, 2002, Pages 13~22
In Korea, 2,320 tonnes of acetanilide were mostly wed as intermediates for synthesis in phar-maceuticals or additives in synthesizing hydrogen peroxide, varnishes, polymers and rubber. Only small amount of 120 kg were wed as a stabilizer for hydrogen peroxide solution for hair colouring agents in 1998. Readily available environmental or human exposure data do not exist in Korea at the present time. However, potential human exposures from drinking water, food, ambient water and in work places are expected to be negligible because this chemical is produced in the closed system in only one company in Korea and the processing factory is equipped with local ventilation and air filtering system. Acetanilide could be distributed mainly to water based on EQC model. This substance is readily biodegradable and its bioaccumulation is low. Acute toxicity of acetanilide is low since the L
of oral exposure in rats is 1,959 mg/kg bw. The chemical is not irritating to skin, but slightly irritating to the eyes of rabbits. horn repeated dose toxicity, the adverse effects in rats were red pulp hyperplasia of spleen, bone marrow hyperplasia of femur and decreased hemoglobin, hematocrit and mean corpuscular hemoglobin concentration. The LOAEL for repeated dose toxicity in rats was 22 mg/kg/day for both sexes. Acetanilide is not considered to be genotoxic. In a reproductive/developmental toxicity study, no treatment-related changes in precoital time and rate of copulation, impregnation, pregnancy were shown in all treated groups. The NOAELs for reproduction and developmental toxicity (off-spring toxicity) are considered to be 200 mg/kg bw/day and 67 mg/kg bw/day, respectively. Ecotoxicity data has been generated in a limited number of aquatic species of algae (72 hr-
; 13.5 mg/l), daphnid (48hr-E
> 100 mg/l) and fish (Oryzias latipes, 96hr-L
; 100 mg/l). Form the acute toxicity values, the predicted no effect concentration (PNEC) of 0.135 mg/1 was derived win an assessment factor of 100. On the basis of these data, acetanilide was suggested as currently of low priority for further post-SIDS work in OECD.in OECD.D.
Initial Risk Assessment of Disodium Disulphite in OECD High Production Volume Chemical Program
Sanghwan Song ; Park, Yoonho ; Park, Hye-Youn ; Kwon, Min-Jeoung ; Koo, Hyun-Ju ; Jeon, Seong-Hwan ; Na, Jin-Gyun ; Park, Kwangsik ;
Toxicological Research, volume 18, issue 1, 2002, Pages 23~29
Disodium disulphite, the HPV chemical, was assigned to Korea in order to implement OECD SIDS program in 1999. It was produced about 3,200 ton/year in 1998. This report evaluates the toxic potency of disodium disulphite based on the environmental and mammalian effects as well as human exposure. Oral
in rats is 1,540 mg/kg b.w. and effects was observed to the stomach, liver and the GI track that was filled with blood. For repeated dose toxicity, the predominant effect was the induction of stomach lesion due to local irritation. The no observed adverse effect lever for local (stomach irritation) was about 217 mg/kg bw/day. There is no evidence that disodium disulphite is genotoxic in vivo. No reproductive or developmental toxicty of disodium disulphite was observed for the period up to 2 yr and over three generation. In humans, urticaria and asthma with itching, edema, rhinitis, and nasal congestion were reported. Disodium disulphite is unlikely to induce respiratory sensitization but may enhance symptom of asthma in sensitive individuals. This chemical would be mainly transported to water compartment when released to environmental compartments since it is highly water soluble (470 g/l at 20). Low K oc (2.447) indicates disodium disulphite is so mobile in soil that it may not stay in the terrestrial compartment. The chemical has been tested in a limited number of aquatic species. hem acute toxicity test to fish, 96 hr-
was > 100 mg/1. For algae, 72 hr-
was 48.1 mg/1. For daphnid, the acute toxicity value of 48 hr-
was 88.76 mg/1, and chronic value of 21day-NOEC was > 10 mg/1. Therefore, PNEC of 0.1 mg/l for the aquatic organism was obtained from the chronic value of daphnid using the assessment factor of 100. Based on these data the disodium disulphite was recommended as low priority for further post-SIDS work in OECD.
A 4-week Repeated Oral Dose Toxicity Study of Plant Sterol Esters in Sprague-Dawley Rats
Kim, Jong-Choon ; Yang, Byung-Chul ; Lim, Kwang-Hyeon ; Kang, Boo-Hyon ; Kim, Choong-Yong ; Kim, Kab-Sik ; Chung, Dae-Won ; Chung, Moon-Koo ;
Toxicological Research, volume 18, issue 1, 2002, Pages 31~41
The present study was conducted to investigate the potential subacute toxicity of plant sterol esters by a 4-week repeated oral dose in Sprague-Dawley rats. The test article was administered once daily by gavage to rats at dose levels of 0, 1000, 3000, and 9000 mg/kg/day for 4 weeks. During the test period, clinical sign, mortality, body weights, food and water consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross finding, organ weight, and histopathology were evaluated. A reduction in the body weight was observed in females of the 9000 mg/kg group on day 27 after the initiation of treatment, but not in males of the group. There were no treatment-related effects on mortality, clinical sign, food and water consumption, ophthalmoscopy, urinarlysis, hematology, serum biochemistry, necropsy findings, organ weights, and histopathology in any treatment group. Based on these results, it was concluded that the 4-week repeated oral dose of plant sterol esters resulted in suppressed body weight in female rats at a dose level of 9000 mg/kg/day. In the condition of this study, target organ was not observed and the no-observed-adverse-effect level (NOAEL) was considered to be 9000 mg/kg/day for males and 5000 mg/kg/day for females.
Case Report of Asbestos Exposure-Related Lung Carcinoma
Chang, Hee-Kyung ; Lee, Yong-Hwan ; Kiyoshi Sakai ; Naomi Hisanaga ; Chung, Yong-Hyun ; Han, Jeong-Hee ; Yu, Il-Je ;
Toxicological Research, volume 18, issue 1, 2002, Pages 43~46
A 61 Year-old female patient was hospitalized for lung cancer. Her Occupational history indicated that she had worked for an asbestos company for 9 years from 1976. The histopathology of the lung revealed malignant bronchioalveolar adenocarcima (stage III) in the lower-left lobe, and a lung sample was found to cantion an unusually high level of asbestos, 218.9
asbestos fibers/g of dry lung tissue. The majority of asbestos fibers found was chrusotile. yet no asbestos body was detected. When compared with Korean male (0.3
fibers/g of dry lung tissue) and female subjects (0.15
fibers/g of dry lung tissue) with no known history of occupational asbestos exposure, the apparent cause of the lung cancer in the current patient was occupational exposure to asbestos.
Two -week Oral Toxicity Study of 1- (4-methylpiperazinyl) -3- phenylisoquinoline (CWJ-a-5) in sprague-Dawley (SD) Rats
Toxicological Research, volume 18, issue 1, 2002, Pages 47~57
The subacute oral toxicity of 1-(4-methylpiperazinyl)-3-phenylisoquinoline (CWJ- a-5) was investigated in Sprague-Dawley (SD) rats. Five groups of 5 males and 5 females were orally administered at doses of 0, 37.5, 75, 150 and 200 mg/kg with CWJ-a-5 for 2 weeks. In clinical signs, Salivation was observed in the 75, 150 and 500 mg/kg male and female groups. Loss of fur was observed in the 500 mg/kg male and female group. Body weight were significantly decreased in the 150 and 500 mg/kg male groups and in the 500 mg/kg female group. Food consumption was significantly decreased in the 300 mg/kg male group. In serum biochemistry, total cholesterol and phospholipid were significantly increased in 500 mg/kg male and female group. Aspartate aminotransferase was significantly increased in the 500 mg/kg female group. In histopathological examination, vacuolar degeneration of renal tubules in the kidney, vacuolar degeneration of hepatocytes in the liver vacuolar degeneration of myocytes in the heart, vacuolar degeneration of histiocytes in the spleen and thymus, atrophy of seminiferous tubule and degeneration of germinal epithelium in the testis, vacuolar degeneration of corpus luteum, granulosa cell and theca cell in the ovary were observed in the 150 and 500 mg/kg male and female groups. Based on these results, the no observed adverse effect level (NOAEL) with CWJ-a-5 was considered to be 75 mg/kg and the absolute toxic dose was considered to be 150 mg/kg in this study
Screening Assay for Identification of Endocrine Disruptors with Androgen Activities using LNCaP Cells
Toxicological Research, volume 18, issue 1, 2002, Pages 59~64
Substantial evidences have been accumulated about the hormone-like effects of exogenous substances such as pesticides and industrial chemicals during past years. The effects of these substances on the endocrine system are believed to be either enhancing or reducing of various endocrine action. It is necessary to identify putative causal agents by the batter system and to assess their ability to disrupt the endocrine system. A variety of in vitro and In vivo approaches have been used to determine the androgenic effects of environmental chemicals. To establish the method for assessment of the putative endocrine disruptors with androgenic activity, we carried out the cell proliferation assay by MTS method after treatment with the various concentration of testosterone in LNCaP cells (human prostatic cancer cell line) and also observed the expression of androgen-related genes by quantitative RT-PCR. In the cell proliferation assay, the results showed that the grouth of LNCaP cells increased within level of at least 10pM testosterone. We measured by quantitative RT-PCR method on the effects of testosterone on mRNA expression of androgen receptor (AR), prostate-specific antigen (PSA), bone morphogenetic protein (BMP) and BMP receptor (BMPR) In LNCaP cells. The results demonstrated that mRNA expression of PSA and BMPR-IB was observed differently within level of at least 0.01 pM testosterone compared with non-treated control. These observations suggest that the detection of PSA and BMPR-IB mRNA by the quantitative RT-PCR in LNCaP cells is very sensitive method to identify the endocrine disruptors to have the androgenic effects.
Estimating Permissible Intake Level for Endosulfan Using Benchmark Dose based on Reproductive Tonicity
Toxicological Research, volume 18, issue 1, 2002, Pages 65~71
A benchmark dose (BMD) approach has been evaluated us a replacement for the traditional NOAEL methodology currently being wed to assess the noncancer effects of toxicants. The endocrine disrupt-ing effect of endosulfan which showed decrement of sperm count and testicular testosterone level in animals, was currently reported. The amount of endosulfan used as pesticide in the country has been continuously increased. The aim of this study was to suggest the permissible intake level (PIL), corresponding to Accept-able Daily Intake (ADI), based on endocrine disrupting effect wing BMD. Various animal data were collected by consideration of critical effect showing endocrine disruption and an animal data for reproductive toxicity was selected. The Power model from BMD software for induction of
having meaning which is the dose at the 95% lower confidence limit on a 10% response was used due to that the form of selected dose-response animal data was continuous data. The
was estimated to be 0.393 mg/kg/day based on reproductive toxicity showing decrement of sperm count. The permissible intake level (PIL) was calculated by dividing the
by the uncertainty factors of 100 with consideration of from animal to human and human variability. The PIL as 0.004 mg/kg/day was compared with traditional ADI as 0.006 mg/kg/day based on the incidence of marked progressive glomerulonephrosis and blood vessel aneurysm in males.
Single Dose Toxicity Study of Hwangiaegongjinbo, an Invigorator, in Mice and Rats
Toxicological Research, volume 18, issue 1, 2002, Pages 73~77
The single dose toxicity of Hwangiaegongjinbo, an invigorator developed by Korea Medical Science Institute was evaluated in ICR mice and Sprague-Dawley rats. The aqueous solution of freeze-dried powder of Hwangiaegongjinbo or its original solution was once administrated orally to both sexes of mice and rats at dose of 2000 mg/kg, the recommended upper limit dose for acute toxicity. Water was administered to another group as control. after single adminstration, sign of toxicity were observed every hour for the first 6 hours and every day for 14 days. Neither sign그cant toxic sign nor death was observed during the observation period. In addition, no pathological changes were noticed in macroscopic examination at necropsy in those treated group. These results indicated that
of Hwangiaegongjinbo is greater than 2000 mg/kg in ICR mice and Sprague-Dawley rats.
Study on Local Irritation in Rabbits and Micronucleus Test in Mice with YHB216
Toxicological Research, volume 18, issue 1, 2002, Pages 79~85
YHB216 is one of new recombinant human erythropoietins (rHu-EPO) developed by Yuhan Research Institute. The rHu-EPO products are widely being used for the treatment of various types of anemia. As a series of safety studies on YHB216, we performed the local irritation test (dermal & ocular application) in male New Zealand White rabbits and micronucleus test in male ICR mice. In the skin irritation test, 0.5 ml of YHB216 10,000 IU/ml solution was applied to the back skin of rabbits for 24 hours and sub-sequent observation was performed. There was no induced response after the treatment and the primary irritation index (P.I.I.) was‘0’. In the eye irritation test, 0.1 ml of YHB216 10,000 IU/mL solution was instilled into the conjunctiva of the eye. No treatment-related reaction was observed at the cornea, iris, and conjunctiva. In the micronucleus test, YHB216 was administered intravenously to male mice (6 mice per group) at dose levels of 0, 6,250, 12,500, and 25,000 IU/kg. Bone marrow cells were collected at 24 hours after the treatment. YHB216 treated groups showed no significant difference in the P/N (polychromatic erythrocyte/ normochromatic erythrocyte) ratio and in the number of micronucleated polychromatic erythrocyte com-pared with the control. In conclusion, YHB216 was found to be a non-irritating material up to 10,000 IU/ml in the local irritation test and to be a non-mutagen up to 25,000 IU/kg in the micronucleus test.
Safety Evaluation of Recombinant Human Factor VIII(GC-γ AHF)
Toxicological Research, volume 18, issue 1, 2002, Pages 87~98
This study was conducted to evaluate the safety of a recombinant human Factor VIII(GC-
AHF) manufactured by Korea Green Cross Company with different technology according to the Regulation of Korean Food and Drug Administration (l 998. 12. 3). In acute toxicity test, both genders of Sprague-Dawley rats and Beagle dogs were administered intravenously with GC-
AHF of three doses (3,125, 625 and 125 IU/kg), and single dose of 3,125 IU/kg, respectively. No dead animal and abnormal autopsy findings were found in Control and GC-
AHF treated group. Therefore, the 50% lethal dose (
) of GC-
AHF was conidered to be higher than 3,125 IU/kg in rats and dogs. In the four weeks repeated intravenous toxicity study, GC-
AHF was administrated intravenosly to both genders of rats and dogs with 3 doses (500, 150, 50 IU/kg). There were neither dead animals nor significant changes of body weights during the experimental Period. In addition, no significant GC-
AHF related changes were found in clinical sign, urinalysis and other finding. Statistically changes were observed in hematological, biochemical and organ weight parameters of treated groups: however these changes were not dose dependent. No histopathological lesion were observed in both control and treated animals. Above data suggest that no observed adverse effect level of test materials in rats and dogs might be over 500 IU/kg/day in this study. In ocular irritation test, any injury on iris, conjunctiva and cornea in rabbits were not observed. The acute ocular irritation index (A.O.I.), mean ocular irritation index (M.O.I.) and Day-7 individual ocular irritation Index (I.O.I.) of GC-
AHF were 0. In the primary skin Irritation test, the primary irritation index (P.I.I.) oj GC-
AHF were 0. Therefore, the GC-
AHF is considered not to have the primary skin and eye toxicity in rabbits. In active systemic anaphylaxis (ASA) test, GC-
AHF and GC-
AHF emulsified with Freund's complete adjuvant (FCA) did not induce any symptom of anaphylactic shock in guinea pigs. In passive cutaneous anaphylxis (PCA) test, after sensitization with antisera of GC-
AHF sensitized mice, blue spots were observed on the hypodermis of back of rats, but diameter of each spot was smaller than 5 mm in each test groups except the positive control group. Based on the results of this study, GC-
AHF is not conidered to have any antigenic potential. In conclusion, at levels of up to 500 IU/kg, GC-
AHF did not produce treatment-related toxicity under the conditions of these acute-, four week repeated-toxicity, primary skin and eye toxicity, and antigenicity test.
A Cancer Risk Assessment of Di (2- ethylhexyl ) -phthalate - Application of MOE (Margin of Exposure) Approach
Toxicological Research, volume 18, issue 1, 2002, Pages 99~106
The United States Environmental Protection Agency (EPA) characterized the cancer hazard of di(2-ethylhexyl)-phthalate (DEHP) as a B2 group (probable human carcinogen) and proposed "Guide-lines for Carcinogen Risk Assessment". This guidelines proposed alternative methods for analyzing carcinogen dose-response data and for extrapolating the effects of observed at high dose to predict that might occur at lower doses relevant to human exposure. This proposed guidelines state that "If in a particular case, the evidence indicated a threshold, as in the case of carcinogenicity being secondary to another toxicity that has a threshold, the margin of exposure analysis for toxicity is the same as is done for a non-cancer endpoint". DEHP is excellent candidate for reconideration under the new guidelines for carcinogen risk assessment (John Doull et al., 1998). This study is conducted about risk assessment for infant exposure on DEHP in powdered milk wing methodology in EPA's new guideline on carcinogenic risk assessment. Estimated cancer risk of DEHP in powdered milk and cow milk is 2.83
(using cancer potency: 1.4
/ (mg/kg/day)) as mean and MOE is 12075 (using selected NOEL 20 mg/kg/day) as mean. mg/kg/day) as mean.