• The Korean Journal of Pesticide Science
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• v.7 no.4
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• pp.280-287
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• 2003

To assess the risk of pesticides on earthworm, the acute toxicities of 10 pesticides were investigated and their toxicity exposure ratios(TERs) were calculated. As the TERs of paraquat dichloride and pendimethalin were more than 100, their risks were rated negligible. Risk of benfuracarb, cadusafos, chlorpyrifos-methyl, endosulfan, isazofos and parathion which have TERs of $10\sim100$ were rated low. However, risk of imidacloprid and phorate which have TER of less than 10 were estimated highly to need a reproduction study. Earthworms were exposed to twenty two pesticides including dazomet 98% GR having PECs of more than $5mg{\cdot}kg^{-1}$ in artificial soil at standard and double dose for 14 days. All the earthworms exposed to dazomet 98% GR and metam-sodium 25% SL were died to show their high risk, while no serious adverse effects were observed in the soil treated with 15 pesticides, calcite 95% WP, calcium polysulfide 36% CF, chlorothalonil 75% WP, daminozide 85% WP, dichlonil 6.7% GR, etridiazole 25% EC, fosetyl-Al 80% WP, glyphosate 41 % SL, hymexazol 30% SL, iprodione 50% WP, machine oil 95% EC, mancozeb 75% WP, propineb 70% WP, terbuthylazine 80% WP and triazophos 40% EC. In case of thiophanate-methyl 70% WP, copper hydroxide 77% WP, dimethoate 46% EC, tolclofos-methyl 50% WP and propamocarb hydrochloride 67% SL, any effect did not show clearly, suggesting an additional subchronic toxicity study. The risk of thiophanate-methyl 70% WP to earthworm was estimated high, considering its subchronic effect, while effects of copper hydroxide 77% WP, dimethoate 46% EC, tolclofos-methyl 50% WP and propamocarb hydrochloride 67% SL to earthworms were negligible, considering no adverse effects in subchronic tests.

• Biomolecules & Therapeutics
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• v.12 no.3
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• pp.138-144
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• 2004

Therapeutic effect of a Kampo medicine, Choto-san, in patients with vascular dementia was demonstrated by a double-blind and placebo-controlled clinical trial. To clarify the therapeutic efficacy of Choto-san, anti-ischemic effect in mice, hypotensive effect in spontaneously hypertensive rats (SHR), anti-oxidative effects in vitro, and N-methyl-D-aspartate (NMDA) receptor-blocking activity using Xenopus oocytes were studied. (1) Pretreatment with Choto-san (0.75-6.O g/kg, P.O.) or a component herb Chotoko (Uncaria genus: 75 - 600 mg/kg, P.O.) prevented ischemia-induced impairment of spatial learning behaviour in mice. Indole alkaloids- and phenolic fractions extracted from Chotoko also improved significantly the learning deficit. (2) Subchronic administration of Choto-san (0.5 g/kg, p.o.) caused a significant hypotensive effects in SHR. (3) Choto-san, Chotoko, and the phenolic constituent, (-) epicatechin, significantly protected the NG108-15 cell injury induced by $H_20_2$ exposure in vitro and also inhibited lipid peroxidation in the brain homogenate. (4) Indole alkaloids, rhynchophylline and isorhynchophylline (1-100 uM), reversibly reduced NMDA-induced current in the receptor-expressed Xenopus oocytes. These results suggest that anti-vascular dementia effects of Choto-san are mainly due to the effect of Chotoko. From these results, it is possible to make a novel dietary supplement through several extraction steps from Chotoko.

• Toxicological Research
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• v.16 no.4
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• pp.302-309
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• 2000

The purpose of this study is to investigate toxic effects of iso-butylalcohol (iBA) in Sprague-Dawley (SD) rats under the exposure of 6 hours a day, 5 days a week for 13 weeks by inhalation, and to evaluate the occupational safety of iBA in comparison with the permissible exposure level (PEL) stipulated by the Occupational Safety and Health Administration (OSHA). iBA did not induce any abnormal changes from the aspects of clinical signs, feed consumption, ophthalmic test, urinalysis, hematology and blood chemistry during and at the terminal of the inhalation toxicity tests. We did not find any abnormal findings in the gross and microscopic observations due to the inhalation of iBA. There was no alteration in relative organ weights by the inhalation of iBA. No observed adverse effect level (NOAEL) of iBA was considered to be more than 3,000 ppm in rats under the inhalation of 6 hours a day, 5 days a week for 13 weeks. Fifty ppm of iBA, the PEL regulated by OSHA, is too conservative for working places. As iBA showed no abnormal observations in all the experimental parameters at any concentration under this experimental condition, we suggest that 150 ppm is safe enough for the PEL of iBA in the working areas, even taking into onsideration that OSHA lowered the PEL to 50 ppm for fear of the probable risk of its skin irritation.

• Environmental Analysis Health and Toxicology
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• v.21 no.2 s.53
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• pp.173-184
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• 2006

From the harmfulness expectation test conducted through a toxicity anticipation program, methylcyclohexane turned out to be harmful and simulative, but no carcinogenicity was anticipated. In a four-hour acute inhalation toxicity test, the result showed that lethal concentration ($LC_{50}$) was 3,750 ppm (15,054 mg/L), which was identified as a harmful substance on the basis of the harmful substance classification standard $2 of the Industrial safety and health law. methylcyclohexane fell under the category $4(2,500 substance from the GHS standard acute toxicity harmfulness classification. Also, from subchronic inhalation toxicity test that included 6 hours a day, five days a week, and for 13 weeks, we could observe weight, activity, long term weight, blood and blood biochemical influence from the exposure of test substance. No-observed effect level (NOEL) was determined below $100{\sim}400ppm$ inboth male and female. This material falls under the Category 2 ($50{\sim}250ppm/6hours/90days$) in the GHS (Globally Harmonized System) standard trace long-term whole body toxicity repeated exposure, and can be classified as a harmful substance in accordance with the Industrial Safety and Health Law harmful substance standard $NOEL{\leq}0.5mg/L/6hr/90day$ (rat).

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.17 no.3
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• pp.181-191
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• 2007

With the 2-Butanethiol, which is an unidentified inhalation toxic material, acute inhalation toxicity was tested with SD rats. The $LC_{50}$ was evaluated to be 2,500 ppm (9.22 mg/L) or higher which falls under the criteria of acute toxicity Category 3 (500<$LC_{50}$<2,500 ppm) in the Industrial Safety and Health Act. In the subchronical inhalation toxicity test by 0, 25, 100, and 400 ppm, 6 hours a day, 5 days a week, for 13 weeks repeated exposure, though no death or particular clinical presentation was observed, in the female 25 and 400 ppm group, including weight change, and in each concentration group including 400 ppm, change of feed rate, eye stimulation, motility change in male group, and lesions in blood and blood biochemical were observed. In the internal organs weight, 25, 100, and 400 ppm groups in male and 400 ppm group in female showed significant (p<0.05) changes in kidney, liver, thymus, and lung. In the pathological tissue test, severe cortical tubular hyaline droplets were observed in the male 400 ppm group, and all male rats of 400 ppm group and 2 female individuals showed tubular degeneration/regeneration accompanied with pigmentation, showing that the target organs of inhalation exposure of 2-Butanethiol are spleen, kidney, nasal cavity, and adrenal. Through the tests, the NOEL of 2-Butanethiol was evaluated to be 25 ppm (0.092 mg/L) or less for both male and female.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.18 no.3
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• pp.224-238
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• 2008

The aim of this study is to confirm the physicochemical property and hazard of thinner (012), which is a diluent of enamel paint used for floor coating for waterproofing and oil painting for the outer wall. The literatures of physicochemical property and hazard of thinner were surveyed and its physicochemical property were evaluated. And then, the inhalation toxicity of thinner affecting the central nervous system and reproductive organs in rats were examined by subchronic (6 h./day. 5 days/ week for 13 weeks) inhalation test. 1) According to the 13-week subchronic inhalation test, there were no significant changes in clinical test and body weight. However, a significant evidence of toxicity was observed in the hematological test and organ weight such as heart, kidney, liver and brain (p<0.01) in the 200 ppm and 1,000 ppm exposure groups in a dose response manner. In the histopathology analysis, there were no significant evidence of toxicity. Therefore, thinner was not classified as an organ targeted toxic agent. In case of Harmfulness, it could be classified as a chronic toxic agent 3($500 ppm/4hr, rat). 2) The reproductive toxicity such as extension of the period of estrous cycle, reduction of serum estradiol concentration and increase of frequency of the abnormal sperm was observed in the 1,000 ppm exposed animals. 3) The result of the physicochemical property of the test material showed that the specific gravity was 0.793, boiling point $155.8^{\circ}C$, steam pressure 2.1 kPa, ignition point $34.5^{\circ}C$, and spontaneous ignition point $280^{\circ}C$. The endothermic and exothermic values were 371.4 J/g and 159.1 J/g. respectively. The explosion limit was 214 mg/l. These data showed that thinner could be classified as an explosion agent level 1.2 and ignitive liquid agent 3 ($23-60^{\circ}C$) according to the notification No. 2008-1 of the Labor Ministry, "Classifying Standard of Chemical Materials."

• Journal of Food Hygiene and Safety
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• v.29 no.2
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• pp.85-91
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• 2014

Deoxynivalenol (DON) and related trichothecene mycotoxins are extensively distributed in the cereal-based food and feed stuffs worldwide. Recent climate changes and global grain trade increased chance of exposure to more DON and related toxic metabolites in poorly managed production systems. Monitoring the biological and environmental exposures to the toxins are crucial in protecting human and animals from toxicities of the hazardous contaminants in food or feeds. Exposure biomarkers including urine DON itself are prone to shift to less harmful metabolites by intestinal microbiota and liver metabolic enzymes. De-epoxyfication of DON by gut microbes such as Eubacterium strain BBSH 797 and Eubacterium sp. DSM 11798 leads to more fecal secretion of DOM-1. By contrast, most of plant-derived DON-glucoside is also easily catabolized to free DON by gut microbes, which produces more burden to body. Phase 2 hepatic metabolism also contributes to the glucuronidation of DON, which can be useful urine biomarkers. However, chemical modification could be very typical depending on the anthropologic or genetic background, luminal bacteria, and hepatic metabolic enzyme susceptibility to the toxins in the diet. After toxin exposure, effect biomarkers are also important in estimating the linkage and mechanisms of foodborne diseases in human and animal population. Most prominent adverse effects are demonstrated in the DON-induced immunological and behavioral disorders. For instance, acutely elevated interleukin-8 from insulted gut exposed to dietaty DON is a dominant clinical biomarker in human and animals. Moreover, subchronic exposure to the toxins is associated with high levels of serum IgA, a biological mediator of IgA nephritis. In particular, anorexia monitoring using mouse models are recently developed to monitor the biological activities of DON-induced feed refusal. It is also mechanistically linked to alteration of serotoin and peptide YY, which are promising biomarkers of neurological disorders by the toxins. As animal-alternative biomonitoring, huamn enterocyte-based assay has been developed and more realistic gut mimetic models would be useful in monitoring the effect biomarkers in resposne to toxic contaminants in the future investigations.

• Korean Journal of Environmental Agriculture
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• v.4 no.2
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• pp.118-125
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• 1985

To establish an evaluation system of aquatic toxicity of chemicals at no-effect level, flow through and early life stage toxicity test were performed on a freshwater fish, the medaka (Oryzias latipes). The characteristics of medaka as a bioassay organism for the chronic toxicity test were discussed. Maximum acceptable toxicant concentration(MATC) of butachlor for the madaka in soft water was estimated using survival, growth, and reproduction as indicators of toxic effects. During a 3-month period, the fry of medaka were exposed to butachor concentrations ranging from 0.16 to 0.0l mg/liter and the DO concentration, temperature, and pH in the exposure chamber were measured to check the test condition. The highest concentration showed slight decrease of growth rate in medaka and reduced hatchability of spawning egg. Survival, growth, and reproductive success of adults in butachlor concentration of 0.04 and 0.01 mg/liter were not different from those of the control. The MATC was estimated to be between 0.04 and 0.16 mg/liter for medaka.

• Toxicological Research
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• v.31 no.2
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• pp.203-211
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• 2015

Trichloroacetonitrile is used as an intermediate in insecticides, pesticides, and dyes. In Korea alone, over 10 tons are used annually. Its oral and dermal toxicity is classified as category 3 according to the globally harmonized system of classification and labelling of chemicals, and it is designated a toxic substance by the Ministry of Environment in Korea. There are no available inhalation toxicity data on trichloroacetonitrile. Thus, the present study performed inhalation tests to provide data for hazard and risk assessments. Sprague-Dawley rats were exposed to trichloroacetonitrile at concentrations of 4, 16, or 64 ppm for 6 hour per day 5 days per week for 13 weeks in a repeated study. As a result, salivation, shortness of breath, and wheezing were observed, and their body weights decreased significantly (p < 0.05) in the 16 and 64 ppm groups. All the rats in 64 ppm group were dead or moribund within 4 weeks of the exposure. Some significant changes were observed in blood hematology and serum biochemistry (e.g., prothrombin time, ratio of albumin and globulin, blood urea nitrogen, and triglycerides), but the values were within normal physiological ranges. The major target organs of trichloroacetonitrile were the nasal cavity, trachea, and lungs. The rats exposed to 16 ppm showed moderate histopathological changes in the transitional epithelium and olfactory epithelium of the nasal cavity. Nasal-associated lymphoid tissue (NALT) and respiratory epithelium were also changed. Respiratory lesions were common in the dead rats that had been exposed to the 64 ppm concentration. The dead animals also showed loss of cilia in the trachea, pneumonitis in the lung, and epithelial hyperplasia in the bronchi and bronchioles. In conclusion, the no-observed-adverse-effect level (NOAEL) was estimated to be 4 ppm. The main target organs of trichloroacetonitrile were the nasal cavity, trachea, and lungs.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.16 no.3
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• pp.233-244
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• 2006

Of many volatile organic detergents for metals, benzine(CAS No. 8030-30-6), of which the toxicity has not yet been proven, has been used as an alternative of the halide compounds in the consideration of toxic effects, global warming and the destruction of ozone layer. In order to evaluate the effects of the benzine on human body by investigating the subchronic inhalation toxicity, to obtain the basic data for establishing the criteria of exposure in working environments and to classify the hazardousness in compliance with the Industrial Safety and Health Act by evaluating the hazardousness, repeated inhalation exposure test was carried with SD rats. The rats were grouped by 10 females and males each. The repetitive inhalation exposures were carried out at 4 levels of concentration of 0 ppm, 60 ppm, 300 ppm, and 1,500 ppm, for 6 hours a day, 5 days a week, for 13 weeks. The results are described hereunder. 1. No death of the animals of the exposed and controlled groups in the test period. Not any specific clinical symptoms, change in feed intake quantity, abnormality in eye test, or change in activity were observed. 2. In the 300 ppm and 1,500 ppm groups, weight reduction in the female groups and weight increase of liver and kidney in the male groups compared with control group were observed with statistical significance(p<0.05). 3. In the blood test, the HCT increased in the male 300 ppm group and the number of hematocyte increased, MCV and MCH decreased in the male 1,500 ppm group. In the female 1,500 ppm group, the HB decreased and the distribution width of the hematocyte particle size increased. In the blood biochemistry test, the TP in the male 1,500 ppm group and the LDH in the female 1,500 ppm group were increased with statistical significance(p<0.05). 4. Under the test conditions of the present study with SD rats, the NOEL was evaluated to be from 60 ppm to 300 ppm for both male and female groups. By extrapolation, the NOEL for human who work 8 hours a day was evaluated to be from 128 ppm to 640 ppm 5. Since the NOEL evaluated in this study do not exceed 60ppm(0.184 mg/L) the test material does not belong to the classification of the hazardous substance "NOEL${\leq}$0.5mg/L/6hr/90day(rat), for continuous inhalation of 6hours a day for 90 days" nor to the basic hazardous chemical substance class 1(0.2 mg/L/6hr/90day(rat) defined by the GHS which is a criteria of classification and identification of chemical compounds. However, considering the boiling point($30-204^{\circ}C$), flashing point($-40^{\circ}C$), vapor pressure(40 mmHg), and the inflammable range(1.0 - 6.0 %), sufficient care should be taken for handling in the safety aspects including fire or explosion.