Park, Chul-Hoon;Sahn, Hyung-Ok;Shin, Han-Jae;Lee, Hyeong-Seok;Min, Yaung-Keun;Hyun, Hak-Chul
Journal of the Korean Society of Tobacco Science
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v.29
no.2
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pp.110-117
/
2007
In vitro toxicity tests such as cytotoxicity, mutagenicity and genotoxicity assay are useful for evaluating the relative toxicity of smoke or smoke condensates obtained from different cigarette configurations. A major disadvantage of these tests is relatively time-consuming, complicated and expensive. Recently, a cell-free glutathione consumption assay (GCA) as a rapid and simple screening method for the toxicity assessment of smoke has been reported by Cahours et al. (CORESTA, 2006). This study was carried out to assess the GCA application capable of predicting the toxicity of gas/vapor phase (GVP) of cigarette smoke and to identify individual compounds responsible for the glutathione (GSH) consumption in smoke. Each GVPs from 2R4F, standard cigarette, carbon filter cigarette (ExC) and new carbon filter cigarette (ExN), test cigarettes were collected by automatic smoking machine and evaluated the relative toxicity by GCA and neutral red uptake (NRU) assay. Toxic compounds existed in smoke were also chosen, relative toxicities of these compounds were screened by using two methods and compared individually. The overall order of toxicity by GCA was 2R4F > ExC > ExN, which was consistent with the result of Neutral Red Uptake assay. The levels of carbonyl compounds of ExN were lower than those of 2R4F and ExC, indicating that GSH consumption was associated with carbonyl compound yields. A major toxicant under current study is acrolein, which contributed to more than half of the GSH consumption. Collectively, the toxicity of GVP determined by GCA method may be mainly attributed to acrolein.
Objectives : Kaempferia parviflora Rhizome is black ginger indigenous to Laos and Thailand. It has been used as a folk medicine to improve blood flow and promote vitality and longevity with good health and well being. For these reasons, Kaempferia parviflora Rhizome has been focused on developing it as a food or food supplement. In addition, Kaempferia parviflora Rhizome could be under consideration of new prescription based on its characteristic compounds, polymethoxyflavonoids. However, it needs to be certified as safe before it can be used. Here, a single-oral toxicity test and safety classification was carried out to identity acute information of the toxicity of Kaempferia parviflora Rhizome powder and to make sure of its safety in clinical applications. Methods : Test substance was orally administered to male and female SD-rat at dose levels of 5000 mg/kg to estimate approximate lethal dose(ALD). Based on the acute information of the toxicity, the safety classification was estimated using the HED(human equivalent dose)-based MOS(margin of safety). Results : At 14 days after treatment with test substance. there were no of test substance related with mortalities and clinical signs. In addition, no changes in the body or organ weights and no gross or histopathological findings were observed. Thus, the ALD of Kaempferia parviflora Rhizome powder was considered over 5,000 mg/kg in both female and male mice. Conclusions : Based on the single oral toxicity test using the highest and limit dose, 5,000 mg/kg and the decision guideline for safety classification based on HED-based MOS, it was estimated that Kaempferia parviflora Rhizome powder is classified as "Specified class B" indicating that clinical dose is not limited to patients as safe as food.
Environmental risk assessment of cadmium compounds was conducted using national monitoring data of aquatic and terrestrial compartments of local area. Aquatic and terrestrial toxicities of cadmium compounds on algae, daphnid, fish, earthworm, springtails and other species were evaluated. The toxicity data evaluated in this study were mainly from ECOTOX database provided by US EPA. Assessment factors were determined according to the EU technical guidance document and/or OECD proposal. Predicted no effect concentration (PNEC) values of aquatic and terrestrial toxicity were 25$\mu\textrm{g}$/L and 0.2 mg/kg, respectively and they were compared with cadmium exposure data of several local areas, which were used as Predicted exposure concentration(PEC) values. Most of the local area were found to be not risky. However, the risk values (PEC/NEC) of some metropolitan areas were greater than 1 when the most conservative PNEC value was applied.
Nephrotoxicity occurs when kidney-specific detoxification and excretion do not work properly due to the damage or destruction of kidney function by exogenous or endogenous toxicants. Exposure to drugs often results in toxicity in kidney which represents the major control system maintaining homeostasis of body and thus is especially susceptible to xenobiotics. Understanding the toxic mechanisms for nephrotoxicity provides useful information on the development of drugs with therapeutic benefits with reduced side effects. Mechanisms for drug-induced nephrotoxicity include changes in glomerular hemodynamics, tubular cell toxicity, inflammation, crystal nephropathy, rhabdomyolysis, and thrombotic microangiopathy. Biomarkers have been identified for the assessment of nephrotoxicity. The discovery and development of novel biomarkers that can diagnose kidney damage earlier and more accurately are needed for effective prevention of drug-induced nephrotoxicity. Although some of them fail to confer specificity and sensitivity, several promising candidates of biomarkers were recently proved for assessment of nephrotoxicity. In this review, we summarize mechanisms of drug-induced nephrotoxicity and present the list of drugs that cause nephrotoxicity and biomarkers that can be used for early assessment of nephrotoxicity.
Kim Mi Kyoung;Bae Heekyung;Kim Su-Hyon;Song Sanghwan;Koo Hyunju;Park Kwangsik;Lee Moon-Soon;Jeon Sung-Hwan;Na Jin-Gyun
Environmental Analysis Health and Toxicology
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v.19
no.1
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pp.33-40
/
2004
Benzoyl peroxide is a High Production Volume Chemical, which is produced about 1,371 tons/year in Korea as of 2001 survey. The substance is mainly used as initiators in polymerization, catalysts in the plastics industry, bleaching agents for flour and medication for acne vulgaris. In this study, Quantitative Structure-Activity Relationships (QSAR) are used for getting adequate information on the physical -chemical properties of this chemical. And hydrolysis in water, acute toxicity to aquatic and terrestrial organisms for benzoyl peroxide were studied. The physical -chemical properties of benzoyl peroxide were estimated as followed; vapor pressure=0.00929 Pa, Log $K_{ow}$ = 3.43, Henry's Law constant=3.54${\times}$10$^{-6}$ atm-㎥/mole at $25^{\circ}C$, the half-life of photodegradation=3 days and bioconcentration factor (BCF)=92. Hydrolysis half-life of benzoyl peroxide in water was 5.2 hr at pH 7 at $25^{\circ}C$ and according to the structure of this substance hydrolysis product was expected to benzoic acid. Benzoyl peroxide has toxic effects on the aquatic organisms. 72 hr-Er $C_{50}$ (growth rate) for algae was 0.44 mg/1.,48 hr-E $C_{50}$ for daphnia was 0.07mg/L and the 96hr-L $C_{50}$ of acute toxicity to fish was 0.24mg/L. Acute toxicity to terrestrial organisms (earth worm) of benzoyl peroxide was low (14 day-L $C_{50}$ = > 1,000 mg/kg). Although benzoyl peroxide is high toxic to aquatic organisms, the substance if not bioaccumulated because of the rapid removal by hydrolysis (half-life=5.2 hr at pH 7 at $25^{\circ}C$) and biodegradation (83% by BOD after 21 days). The toxicity observed is assumed to be due to benzoyl peroxide rather than benzoic acid, which shows much lower toxicity to aquatic organisms. One can assume that effects occur before hydrolysis takes place. From the acute toxicity value of algae, daphnia and fish, an assessment factor of 100 was used to determine the predicted no effect concentration (PNEC). The PNEC was calculated to be 0.7$\mu\textrm{g}$/L based on the 48 hr-E $C_{50}$ daphnia (0.07 mg/L). The substance shows high acute toxicity to aquatic organisms and some information indicates wide-dispersive ore of this substance. So this substance is, a candidate for further work, even if it hydrolysis rapidly and has a low bioaccumulation potential. This could lead to local concern for the aquatic environment and therefore environmental exposure assessment is recommended.
Perfluorinated Compounds (PFCs) are anthropogenic compounds found in trace amounts in many environmental compartments far from areas of production. Along with the highly persistent nature of PFCs, there are increasing concerns over the potential adverse effects of them on the ecosystems. Most of highly fluorinated compounds degrade into PFOS and PFOA that are very stable compounds hard to break down. So, in this study, we tried to determine the toxicity of PFOS and PFOA in the terrestrial invertebrate. Acute toxicity test using earthworm, Eisenia fetida, was performed according to the OECD test guideline 207 (Earthworm, Acute Toxicity Tests). In the 14 day acute toxicity tests, the highest concentration causing no mortality and the lowest concentration causing 100% mortality of PFOS were 160 and 655 mg/kg (dry weight), respectively. And the highest concentration causing no mortality and the lowest concentration causing 100% mortality were 500 and 1,690 mg/kg (dry weight), respectively in the PFOA-exposure group. 14 day-LC50 values were estimated at the level of 365 and 1,000 mg/kg (dry weight) in the PFOS and PFOA-exposed group. These results indicate that under laboratory conditions PFOS is about 3 times more toxic to earthworms than PFOA. Based on known environmental concentrations of PFOS in the soil of Korea, which occur in the 0.42~0.73 ng/L range, there is no apparent risk to terrestrial invertebrate, earthworms. However, further work is required to investigate long-term effects on these and other terrestrial organisms.
The methods used for risk assessment from exposure to chemicals are well established. in most cases where toxicity other than carcinogenesis is being considered, the standard method relies on establishing the No Observed Adverse Effect Level (NOAEL) in the most sensitive animal toxicity study and using an appropriate safety factor (SF) to determine the exposure which would be associated with an acceptable risk. For carcinogens a different approach is used because it has been argued there is no threshold of effect. Thus mathematical equations are used to extrapolate from the high doses used in ani-mal experiments. These methods have been strongly criticised in recent years on several grounds. The most cogent criticisms are a) the equations are not based on a thorough understanding of the mechanisms of carcinogenesis and b) the outcome of a risk assessment based on such models varies more as a consequence of changes to the assumptions and equation used than it does from the data derived from carcinogenicity experiments. Other criticisms include the absence of any measure of the variance on the risk assessment and the selection of default values that are very conservative. Recent advances in the application of risk assessment emphasise that measures of both the exposure and the hazard should be considered as a distribution of values. The outcome of such a risk assessment provides an estimate of the distribution of the risks.
The genetic toxicity of environmental pollutants, namely, nonylphenol (NP), bisphenol A (BPA) and chloropyriphos (CP) was investigated in aquatic sentinel species, freshwater crustacean, Daphnia magna, and larva of aquatic midge, Chironomus tentans, using Comet assay. Physiological effect of such pollutants was also investigated by studying the specimens' rates of reproduction, growth and survival. Acute toxicity results showed that, as expected, Daphnia was more sensitive than Chironomus to chemical exposure. The order of acute toxicity was CP > NP > BPA in D. magna and NP > CP > BPA in C. tentans. BPA may exert a genotoxic effect on D. magna and C. tentans, given that DNA strand breaks increased in both species exposed to this compound, whereas NP- and CP-induced DNA damage occurred only in C. tentans. In vivo genotoxic data obtained in aquatic sentinel species could provide valuable information for freshwater quality monitoring. The experiments with NP-exposed D. magna showed that the pollutant has long-term effects on reproduction, whereas no short-term effect on DNA integrity was found, being an example of a false-negative result from the biomarkers perspective. This result could be interpreted that other mechanism than genetic alteration might be involved in NP-induced reproduction failure in D. magna. False-positive results from the genotoxic biomarker obtained in BPA-exposed D. magna and in NP-exposed C. tentans make it difficult to use DNA integrity as an early warning biomarker. However, as the mere presence of genotoxic compounds, which are potentially carcinogenic, is of high concern to human and ecosystem health, it could also be important to rapidly and effectively detect genotoxic compounds in the aquatic system in ways that do not necessarily accompany a higher level of alteration. Considering the potential of D. magna and C. tentans as bioindicator species, and the importance of genotoxic biomarkers in ecotoxicity monitoring, DNA damage in these species could provide useful information for environmental risk assessment.
Objectives For successful adoption of legislation controlling registration and assessment of chemical substances, it is important to obtain sufficient toxicological experimental evidence and other related information. It is also essential to obtain a sufficient number of predicted risk and toxicity results. Particularly, methods used in predicting toxicities of chemical substances during acquisition of required data, ultimately become an economic method for future dealings with new substances. Although the need for such methods is gradually increasing, the-required information about reliability and applicability range has not been systematically provided. Methods There are various representative environmental and human toxicity models based on quantitative structure-activity relationships (QSAR). Here, we secured the 10 representative QSAR-based prediction models and its information that can make predictions about substances that are expected to be regulated. We used models that predict and confirm usability of the information expected to be collected and submitted according to the legislation. After collecting and evaluating each predictive model and relevant data, we prepared methods quantifying the scientific validity and reliability, which are essential conditions for using predictive models. Results We calculated predicted values for the models. Furthermore, we deduced and compared adequacies of the models using the Alternative non-testing method assessed for Registration, Evaluation, Authorization, and Restriction of Chemicals Substances scoring system, and deduced the applicability domains for each model. Additionally, we calculated and compared inclusion rates of substances expected to be regulated, to confirm the applicability. Conclusions We evaluated and compared the data, adequacy, and applicability of our selected QSAR-based toxicity prediction models, and included them in a database. Based on this data, we aimed to construct a system that can be used with predicted toxicity results. Furthermore, by presenting the suitability of individual predicted results, we aimed to provide a foundation that could be used in actual assessments and regulations.
Journal of the Korean Society of Urban Environment
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v.18
no.4
/
pp.547-555
/
2018
In addition to North America and Europe, Korea is also responding to the toxic damage caused by the production and distribution of chemicals. Methods for assessing bio-toxicity of harmful substances have been widely introduced, but it is required of quantitative and speedy information for modeling. For 6 heavy metals, as zinc, copper, chrome, cadmium, mercury and lead, bio-toxicity assessment and kinetics model were constructed using Vibrio fischeri which is widely used luminous bacteria. The degree of luminescence activity and the toxicity of heavy metals were relative limunescence unit, RLU measured as by using a photomultiplier embedded device. The toxicity was assessed by the concentration levels giving under 20% lethality and lethal concentration, $EC_{50}$. In the results, the toxicity order were followed from mercury, lead, copper, chrome, zinc and cadmium. $EC_{{50},{\infty}}$ obtained by trends of $EC_{50}$ by time follows had highly linear agreement with main parameters of bio-toxicity modelling. The average error rates of the reproduced lethality obtained from DAM and TDM model on the basis of body residue, were 10.2% for mercury, lead, copper, chrome and 20.0 for the all 6 methals.
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