• Environmental Mutagens and Carcinogens
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• v.16 no.1
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• pp.1-5
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• 1996

Fumonisin B$_1$ is hepatotoxic in all species, but liver carcinogenic and nephrotoxic in rat. Our objective was to investigate the effects of multiple iv dose of FB$_1$. Male Sprague-Dawley rats were injected intravenously (iv) with FB$_1$ at 1 mg/kg singly (T1), or daily for 2 (T2) or 3 (T3). T1 rats did not show any cytotoxicity in both liver and kidney. However, the most dramatic change occurred in this group was mitotic figures in liver, which increased 5.5-fold to that of control. Hepatotoxic effects were shown in T3, based on histopathology and serum chemistry. A few scattered single cell deaths occurred primarily in the centrilobular area of the liver in T2. Similar but more lesions in liver and a small number of degenerating cells with hypereosinophilic cytoplasm in outer stripe of medulla of kideny were found in T3 rats. Serum chemical profiles included liver enzymes increased, in which cholesterol was very sensitive. This study suggests that multiple exposure of low dose FB$_1$ cause cytotoxic in the liver earlier time point than kideny. FB$_1$$ also stimulates mitosis in liver that may be associated with carcinogenesis.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.25 no.2
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• pp.134-145
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• 2015

Objectives: An objective of this study was to perform a risk assessment and social cost-benefit analysis for revising permissible exposure limits for seven substances: Nickel(Insoluble inorganic compounds), benzene, carbon disulfide, formaldehyde, cadmium(as compounds), trichloroethylene, touluene-2,4-diisocyanate. Materials and Methods: The research methods were divided into risk and hazard assessment and cost-benefit analysis. The risk and hazard assessment for the seven substances consists of four steps: An overview of GHS MSDS(1st), review of document of ACGIH's TLVs (2nd), comparison between international occupational exposure limits and domestic permissible exposure limits(3rd), and analysis of excess workplace and excess rate for occupational exposure limits based on previous work environment measurement data(4th). Total cost was estimated using cost of local exhaust ventilation, number of excess workplace and penalties for exceeding a permissible exposure limit. On the other hand, total benefit was calculated using the reduction rate of occupational disease, number of workplaces treating each substance and industrial accident compensation. Finally, the net benefit was calculated by subtracting total cost from total benefit. Results: All the substances investigated in this study were classified by CMR(Carcinogens, Mutagens or Reproductive toxicants) and their international occupational exposure limits were stricter than the domestic permissible exposure limits. As a result of excess rate analysis, trichloroethylene was the highest at 11%, whereas nickel was the lowest at 0.5%. The excess rates of all substances except for trichloroethylene were observed at less than 10%. Among the seven substances, the total cost was highest for trichloroethylene and lowest for carbon disulfide. The benefits for the seven substances were higher than costs estimated based on strengthening current permissible exposure limits. Thus, revising the permissible exposure limits of the seven substances was determined to be acceptable from a social perspective. Conclusions: The final revised permissible exposure limits suggested for the seven substances are as follows: $0.2mg/m^3$ for nickel, 0.5 ppm(TWA) and 2.5 ppm(STEL) for benzene, 1 ppm(TWA) for carbon disulfide, $0.01mg/m^3$(TWA) for cadmium, 10 ppm(TWA) and 25 ppm(STEL) for trichloroethylene, 0.3 ppm(TWA) for formaldehyde, and 0.005 ppm(TWA) and 0.02 ppm(STEL) for toluene diisocynate(isomers).

• Korean Journal of Head & Neck Oncology
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• v.19 no.2
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• pp.148-157
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• 2003

Background and Objectives: Individual genetic susceptibilities to chemical carcinogens have been recognized as a major important host factors in human cancers. The cytochrome P450 family (CYPs) and glutathione S-transferase(GST) have been reported to be associated with risks to the smoking-related human cancers. Inactivation of tumor suppressor genes like p53 playa key role in tumor progression. The purpose of this study is to demonstrate an association between p53 overexpression and the prevalence of the genetic polymorphisms of CYP1A1 and GSTs in Korean head and neck squamous cell carcinoma (HNSCC). Materials and Methods: The polymorphisms of CYPIA1 and GSTs were analyzed by PCR and PCR-RFLP in 98 Korean head and neck squamous cell carcinoma patients. The expression of p53 was analyzed by immunohistochemistry with anti-p53 Ab (DO7). Results: Overexpression of p53 detected in 45.9% of HNSCC. The odds ratio for p53 overexpression in GSTM1(-), GSTT1(-), GSTP1(val/val) and CYP1A1(val/val) were 1.53, 1.83, 1.17 and 1.47, respectively. Among the combined genotypes, the odds ratio of the CYP1A1 val/val, GSTM1 (-), CYP1A1 val/val, GSTT1(-), and CYP1A1 val/val, GSTT1(-) were 2.0, 2.34 and 4.68, respectively. Conclusion: Based on our results, it might be suggested that p53 overexpression is slightly increased in GSTM1(-), GSTT1(-), GSTP1 val/val, CYP1A1 val/val genotypes. The further study is needed to evaluate the relationship and mechanism between the p53 overexpression and the specific CYP1A1 and GSTs genotypes.

• Archives of Pharmacal Research
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• v.25 no.5
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• pp.655-663
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• 2002

Liver fibrosis is a prepathological state wherein damaged liver tissues in chronic liver diseases, such as hepatitis, are not repaired to normal tissues, but converted to fibrous tissue. 5-(2-Pyrazinyl)-4-methyl-1,2-dithiol-3-thione (oltipraz), a cancer chemopreventive agent, is effective against a wide variety of chemical carcinogens. Recently, we reported that oltipraz inhibits liver fibrogenesis (Kang et al., 2002). In the present study, the effects of oltipraz in combination with dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylene dioxybiphenyl-2,2'-dicarboxylate (DDb) on dimethylnitrosamine (DMN)-induced liver fibrogenesis were assessed in rats. Oltipraz (30 mg/kg body weight, po, 3 times per week for 4 weeks) was found to inhibit the increases in plasma ALT, AST and bilirubin by DMN, whereas DDB (30 mg/kg body weight, po, 3 times per week for 4 weeks) attenuated the increases in the plasma ALT and bilirubin. The lowered plasma protein and albumin contents in DMN-treated rats were completely restored by oltipraz, but not by DDB. DDB decreases liver cell injury and inflammation through inhibition of nuclear factor-kB. DMN increased the accumulation of liver collagen, as indicated by the increase in the 4-hydroxyproline content in liver homogenates, which was reduced by treatment with oltipraz, but not by DDB. Given the differential effect between oltipraz and DDB, the potential enhancement of antifibrotic efficacy by the drugs was assessed in the animal model. Despite the minimal effect of DDB on DMN-induced fibrogenesis, DDB (5-25 mg/kg), administered together with oltipraz (25-5 mg/kg), showed an additive protective effect against hepatotoxicity and fibrosis induced by DMN, which was shown by the blood chemistry parameters and histopathological analysis. The adequate composition ratio of oltipraz to DDB was 5:1. These results provide information on the pharmaceutical composition, comprising of oltipraz and DDB as the active components, for the treatment and/or prevention of liver fibrosis and cirrhosis.

• Environmental Mutagens and Carcinogens
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• v.21 no.1
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• pp.1-8
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• 2001

We have synthesized $^{99m}$Tc-mercaptoacetyltriglycine (MAG3)-biocytin as a new imaging agent for hepatobiliary scintigraphy. The aim of this study was to evaluate the usefulness of $^{99m}$Tc-MAG3-biocytin scintigraphy in differentiating carbon tetrachloride ( $CCl_4$)-induced hepatotoxicity from $\alpha$-naphthylisothiocyanate (ANIT)-induced cholestasis in mice, which reflecting the differential diagnosis of neonatal jaundice caused by neonatal hepatitis from congenital biliary atresia in humans. Methods: Balb/c mice (female, 20 g, n=4-6) were pretreated with $CCl_4$(0.5 or $1.0m\ell$/kg) and ANIT ($150 or 300 m\ell$/kg) 18 h before scintigraphy. Biochemical and histopathological examinations showed a pattern of typical acute hepatitis (increase of transaminases and hepatocellular necnsis) in $CCl_4$-treated mice and cholestasis (increase of alkaline phosphatase and ${\gamma}$-glutamyltransferase, and biliary hyperplasia) in ANIT-treated mice, respectively, Mice were fasted at least 4 hr prior to the intravenous injection of $^{99m}$Tc-MAG3-biocytin (18.5 MBq/20$\mu\textrm{g}$) in 2% human serum albumin in saline. Scintigraphy was performed with a ${\gamma}$-camera equipped with a 1-mm diameter pin-hole collimator for 30 min and images were acquired every 15 s. We compared the values of physical parameters, such as peak liver/heart ratio ($${\gamma}$_{max}$) and peak ratio time ($t_{max}$) far $^{99m}$Tc-MAG3-biocytin scintigraphy. Results: Scintigraphic parameters of the $CCl_4$-pretreated (0.5 $m\ell$/kg) group showed a 81.9% decrease of r$_{max}$, and 42.2% decrease of $t_{max}$, whereas the ANIT-pretreated ( $150m\ell$/kg) group showed a 53% decrease of $r_{max}$, and 2.36-fold increase of $t_{max}$, (P<0.05). These results demonstrate that the decrease of $r_{max}$ and the shortening of $t_{max}$ are characteristic features for hepatotoxicity, in contrast to the increase of $t_{max}$ and decrease of $r_{max}$ for biliary hyperplasia. Conclusion: $^{99m}$Tc-MAG3-biocytin hepatobiliary scintigraphy can distinguish hepatitis from cholestasis in mice model and may be similarly useful in humans which differentiating the cause of neonatal jaundice in clinical study.cal study.cal study.cal study.

• Environmental Analysis Health and Toxicology
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• v.12 no.3_4
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• pp.31-41
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• 1997

Public concerns about hazardous health effect from the exposure to organic by-products of the chlorination have been increased. There are numerous studies reporting that chlorination of drinking water produces numerous chlorinated organic by-products including THMs, HAAs, HANs. Some of these products are known to be animal carcinogens. The purpose of this study was to estimate health risk of DBPs by chlorinated drinking water ingestion in Seoul based on methodologies that have been developed for conducting risk assessment of complex-chemical-mixture. The drinking water sample was collected seperately at six water treatment plant in Seoul at March, April, 1996. In tap water of households in Seoul, DBPs were measured wilfh the mean value of 36.6 $\mu$g/L. Risk assessment processes,. which include processes for the estimation of human cancer potency using animal bioassay data and calculation of human exposure, entail uncertainties. In the exposure assessment process, exposure scenarios with various assumptions could affect the exposure amount and excess cancer risk. The reference dose of haloacetonitriles was estimated to be 0.0023 mg/kg/day by applying dibromoacetonitrile NOAEL and uncertainty factor to the mean concentration. In the first case, human excess cancer risk was estimated by the US EPA method used to set the MCL (maximum contaminant level). In the second and third case, the risk was estimated for multi-route exposure with and without adopting Monte-Carlo simulation, respectively. In the second case, exposure input parameters and cancer potencies used probability distributions, and in the third case, those values used point estimates (mean, and maximum or 95% upper-bound value). As a result, while the excess cancer risk estimated by US EPA method considering only direct ingestion tended to be underestimated, the risk which was estimated by considering multi-route exposure without Monte-Carlo simulation and then using the maximum or 95% upper-bound value as input parameters tended to be overestimated. In risk assessment for Trihalomethanes, considering multi-route exposure with adopting Monte-Carlo analysis seems to provide the most reasonable estimations.

• Safety and Health at Work
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• v.7 no.1
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• pp.63-71
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• 2016

Background: Construction painters have not been studied well in terms of their hazards exposure. The objective of this study was to evaluate the exposure levels of total volatile organic compounds (TVOCs) for painters in the construction industry. Methods: Activity-specific personal air samplings were carried out in three waterproofing activities [polyurethane (PU), asphalt, and cement mortar] and three painting activities (epoxy, oil based, and water based) by using organic-vapor-monitor passive-sampling devices. Gas chromatograph with flame ionization detector could be used for identifying and quantifying individual organic chemicals. The levels of TVOCs, by summing up 15 targeted substances, were expressed in exposure-index (EI) values. Results: As arithmetic means in the order of concentration levels, the EIs of TVOCs in waterproofing works were 10.77, 2.42, 1.78, 1.68, 0.47, 0.07, and none detected (ND) for indoor PU-primer task, outdoor PU-primer task, outdoor PU-resin task, indoor PU-resin task, asphalt-primer task, asphalt-adhesive task, and cement-mortar task, respectively. The highest EI for painting works was 5.61 for indoor epoxyprimer task, followed by indoor epoxy-resin task (2.03), outdoor oil-based-spray-paint task (1.65), outdoor water-based-paint task (0.66), and indoor oil-based-paint task (0.15). Assuming that the operations were carried out continuously for 8 hours without breaks and by using the arithmetic means of EIs for each of the 12 tasks in this study, 58.3% (7 out of 12) exceeded the exposure limit of 100% (EI > 1.0), while 8.3% (1 out of 12) was in 50e100% of exposure limit (0.5 > EI > 1.0), and 4 tasks out of 12 were located in less than 50% of the limit range (EI < 0.5). Conclusion: From this study, we recognized that construction painters are exposed to various solvents, including carcinogens and reproductive toxins, and the levels of TVOC concentration in many of the painting tasks exceeded the exposure limits. Construction workers need to be protected from chemical agents during their painting works by using personal protective devices and/or work practice measures. Additional studies should focus on the exposure assessment of other hazards for construction workers, in order to identify high-risk tasks and to improve hazardous work environments.

• Korean Journal of Environmental Agriculture
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• v.30 no.1
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• pp.24-30
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• 2011

BACKGROUND: High input to the arable land is contributed to increasing productivity with causing the global environmental problems at the same time. Rapeseed cultivation has been forced to reassess its positive point for utilization of winter fallow field. The Objective of this study was performed to assess the environmental impact of rapeseed cultivation with double-cropping system in paddy rice on Yeonggwang district using life cycle assessment technique. METHODS AND RESULTS: For assessing each stage of rapeseed cultivation, it was collected raw data for input materials as fertilizer and pesticide and energy consumption rate by analyzing the type of agricultural machinery and working hours by 1 ton rapeseed as functional unit. Environmental impacts were evaluated by using Eco-indicator 95 method for 8 impact categories. It was estimated that 216 kg $CO_2$-eq. for greenhouse gas, 3.98E-05 kg CFC-11-eq. for ozone lazer depletion, 1.78 kg SO2-eq. for acidification, 0.28 kg $PO_4$-eq. for eutrophication, 5.23E-03 kg Pb-eq. for heavy metals, 2.51E-05 kg B(a)p-eq. for carcinogens, 1.24 kg SPM-eq. for smog and 6,460 MJ LHV for energy resource are potentially emitted to produce 1 ton rapeseed during its whole cultivation period, respectively. It was considered that 90% of these potential came from chemical fertilizer. For the sensitivity analysis, by increasing the productivity of rapeseed by 1 ton per ha, potential environmental loading was reduced at 22%. CONCLUSION(s): Fertilization affected most dominantly to the environmental burden, originated from the preuse stage, i.e. fertilizer manufacturing and transporting. It should be included and assessed an indirect emission, which is not directly emitted from agricultural activities. Recycling resource in agriculture with reducing chemical fertilizer and breeding the high productive variety might be contribute to reduce the environmental loading for the rapeseed cultivation.

• Journal of the Korean Society of Food Science and Nutrition
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• v.26 no.2
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• pp.186-192
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• 1997

Increased activities of phase 2 enzymes including quinone reductase(QR) have been reported to be associated with protection of animals from neoplastic, mutagenic, and other toxic effects of many carcinogens. In previous study, we found that methanol extract of roasted and defatted perilla meal induced the activity of quinone reductase, an anticarcinogenic marker enzyme, in murine hepalc1c7 cells. Current study showed that unroasted perilla had a limited QR-inducing activity, suggesting that roasting cause the generation of active component(s). Thus we hypothesized that QR inducer in perilla might be covalently linked to sugar moiety and released during roasting process. Methanol extract of defatted raw perilla was subject to acid treatment in order to hydrolyze the potential sugar moiety. Prolonged hydrolysis of methanol extract of defatted raw perilla at $98{\sim}100^{\circ}C$ increased the ability to induce cytosolic QR activity of hepalclc7 cells. Furthermore roasting at 180 and $200^{\circ}C$ resulted in significant induction of QR activity. The result strongly support the idea that QR inducer(s) is present in bound form in raw perilla and released during roasting. Cellular QR activity was induced proportionately with the increase of concentration of methanol extract of roasted perilla. The induction of QR by defatted perilla was also examined in the cytosols of liver, small intestine, stomach, lung and kidney of male ICR mice. Induction patterns showed specificity with respect to target tissue and roasting of perilla. Unroasted perilla meal (defatted) significantly induced QR in liver and lung, while roasted perilla meal induced QR in liver and stomach. The observation that raw perilla showed similar QR induction patterns to roasted perilla is consistent with our proposal that QR inducer(s) is present in bound form and released by physical and chemical treatments as digestive or microbial enzymes could release the inducers from inactive glycoside forms in gastrointestinal tract of mice. In conclusion, perilla could exert protective effect against chemically induced carcinogenesis by inducing phase 2 enzymes in biological systems regardless of chemical and physical process such as roasting.

• Journal of Food Hygiene and Safety
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• v.14 no.4
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• pp.319-326
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• 1999

Recently, it is continuously rising to concern about the health risk being induced by microorganisms in food such as Escherichia coli O157:H7 and Listeria monocytogenes. Various organizations and regulatory agencies including U.S.FPA, U.S.DA and FAO/WHO are preparing the methodology building to apply microbial quantitative risk assessment to risk-based food safety program. Microbial risks are primarily the result of single exposure and its health impacts are immediate and serious. Therefore, the methodology of risk assessment differs from that of chemical risk assessment. Microbial quantitative risk assessment consists of tow steps; hazard identification, exposure assessment, dose-response assessment and risk characterization. Hazard identification is accomplished by observing and defining the types of adverse health effects in humans associated with exposure to foodborne agents. Epidemiological evidence which links the various disease with the particular exposure route is an important component of this identification. Exposure assessment includes the quantification of microbial exposure regarding the dynamics of microbial growth in food processing, transport, packaging and specific time-temperature conditions at various points from animal production to consumption. Dose-response assessment is the process characterizing dose-response correlation between microbial exposure and disease incidence. Unlike chemical carcinogens, the dose-response assessment for microbial pathogens has not focused on animal models for extrapolation to humans. Risk characterization links the exposure assessment and dose-response assessment and involve uncertainty analysis. The methodology of microbial dose-response assessment is classified as nonthreshold and thresh-old approach. The nonthreshold model have assumption that one organism is capable of producing an infection if it arrives at an appropriate site and organism have independence. Recently, the Exponential, Beta-poission, Gompertz, and Gamma-weibull models are using as nonthreshold model. The Log-normal and Log-logistic models are using as threshold model. The threshold has the assumption that a toxicant is produce by interaction of organisms. In this study, it was reviewed detailed process including risk value using model parameter and microbial exposure dose. Also this study suggested model application methodology in field of exposure assessment using assumed food microbial data(NaCl, water activity, temperature, pH, etc.) and the commercially used Food MicroModel. We recognized that human volunteer data to the healthy man are preferred rather than epidemiological data fur obtaining exact dose-response data. But, the foreign agencies are studying the characterization of correlation between human and animal. For the comparison of differences to the population sensitivity: it must be executed domestic study such as the establishment of dose-response data to the Korean volunteer by each microbial and microbial exposure assessment in food.