• Toxicological Research
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• v.27 no.3
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• pp.133-135
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• 2011

The FDA guidance focuses on the use of the NOAEL to establish the maximum recommended starting dose. The majority of NOAEL has been described inaccurately or incompletely in final reports for 90-days repeated dose toxicity test based on GLP (good laboratory practice) regulation. This is the most serious one of reasons for why most pharmaceutical companies targeting global markets have disregarded the final report produced from GLP facilities in Korea. The problems in deciding NOAEL reflected in the final reports are mainly due to the followings; 1) Inaccurate description or use of NOEL, NOAEL and LOAEL, 2) Insufficient and inappropriate interpretations in findings from toxicity test. This paper is intended to provide the insight into distinguishing NOAEL from NOEL and LOAEL, and into classifying findings from toxicity test. Here, the three step method is newly suggested by applying the weight-based classification to the NOEL, NOAEL and LOAEL based on the findings.

• Journal of Korean Society of Environmental Engineers
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• v.33 no.1
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• pp.60-70
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• 2011

The sediment removal index derived from the chemical contaminants, $CI_{HC}$, is currently in use to identify and define the spatial extent of the contaminated sediments in the sea. In order to analyze the sensitivity of the ecological and human risk associated with contaminated sediment, we evaluated five hypothetical contaminated sediments, whose $CI_{HC}$ values are identical but consisted of different contaminant contents, using $TrophicTrace^{(R)}$ model dedicated to evaluate sediment risk, against the resident greenling (Hexagrammos otakii) and humans by calculating No-Observed-Adverse-Effect-Level based Toxicity Quotient (NOAEL TQ) and Lowest-Observed-Adverse-Effect-Level based Toxicity Quotient (LOAEL TQ), and cancer risks and hazard indices (HI), respectively, based on the site conceptual model and exposure assumptions of fish ingestion to human receptor populations. NOAEL and LOAEL TQ values varied as much as a factor of 2 among 5 hypothetical sediments. Chemical element specific contribution to the carcinogenic risk and HI varied also greatly in these sediments. The reason for this significant dissimilarity in ecological and human risk stems from the different risk of each contaminant to the resident fish and human receptor. When the conceptual food web model is constructed for the target biological species for a given site, the ecological and human risk analysis considering trophic transfer of contaminants will add a ecosystem based tool for the management of contaminated sediments.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.22 no.3
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• pp.235-243
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• 2012

Objectives: The purpose of this study is the work environment management method through risk assessment and investigation of the work place that deals with Ammonium nitrate, based on information in and outside the country. Methods: This study suggests method of work environment management through risk assessment and investigation of the work place that deals with Ammonium nitrate, and finds out cases of Ammonium nitrate causing hazard, danger and health risk, based on literature investigation. Results: Rats exposed repeatedly to $LD_{50}$ 2,217 mg/kg(rat), $LC_{50}$ 88.8 mg/L(rat, skin) which cause high level of skin irritation, reported 1 $mg/m^3$ of NOAEL, while LOAEL was less than 100 mg/kg for the rats orally administered with the $LD_{50}$ 2,217 mg/kg(rat), $LC_{50}$ 88.8 mg/L(rat, skin), for 13 weeks. Domestically 31,640 ton/y of ammonium nitrate has been used in 22 workplace and the result of workplace assessment was 0.0171-0.9983 $mg/m^3$. ADD was 8.77-59.63 ${\mu}g/kg-day$ according to the exposure scenario. In other words the result of the risk assessment goes beyond the 'standard 1'. Conclusions: Ammonium nitrate creates a high level of irritation and toxicity when coming in breathe it or contact with skin, and is classified as category3 of GHS and specific target organ toxicant (irritating respiratory system). Exposure level at work places needs to be maintained under $1mg/m^3$, to prevent workers from being damaged.

• Toxicological Research
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• v.18 no.1
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• pp.13-22
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• 2002

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 $D_{50}$ 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- $E_{b}$ $C_{50}$; 13.5 mg/l), daphnid (48hr-E $C_{50}$ > 100 mg/l) and fish (Oryzias latipes, 96hr-L $C_{50}$; 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.

• Toxicological Research
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• v.31 no.4
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• pp.371-392
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• 2015

TS-DP2 is a recombinant human granulocyte colony stimulating factor (rhG-CSF) manufactured by TS Corporation. We conducted a four-week study of TS-DP2 (test article) in repeated intravenous doses in male and female Sprague-Dawley (SD) rats. Lenograstim was used as a reference article and was administered intravenously at a dose of $1000{\mu}g/kg/day$. Rats received TS-DP2 intravenously at doses of 250, 500, and $1000{\mu}g/kg/day$ once daily for 4 weeks, and evaluated following a 2-week recovery period. Edema in the hind limbs and loss of mean body weight and body weight gain were observed in both the highest dose group of TS-DP2 and the lenograstim group in male rats. Fibro-osseous lesions were observed in the lenograstim group in both sexes, and at all groups of TS-DP2 in males, and at doses of TS-DP2 $500{\mu}g/kg/day$ and higher in females. The lesion was considered a toxicological change. Therefore, bone is the primary toxicological target of TS-DP2. The lowest observed adverse effect level (LOAEL) in males was $250{\mu}g/kg/day$, and no observed adverse effect level (NOAEL) in females was $250{\mu}g/kg/day$ in this study. In the toxicokinetic study, the serum concentrations of G-CSF were maintained until 8 hr after administration. The systemic exposures ($AUC_{0-24h}$ and $C_0$) were not markedly different between male and female rats, between the administration periods, or between TS-DP2 and lenograstim. In conclusion, TS-DP2 shows toxicological similarity to lenograstim over 4-weeks of repeated doses in rats.

• Journal of Environmental Health Sciences
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• v.31 no.6
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• pp.457-466
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• 2005

Industrial plasticizers such as phthalates can induce peroxisome proliferation. A growing concern among environmental and health groups has arisen because phthalates such as di-2-ethy1hexy1 phthalate (DEHP) and DBP may cause hormonal disorders, reproductive toxicity, hepatocellular tumors, genital disorders owing to a capacity to bind estrogen receptors, and a low-dose toxic action during certain periods of fetal development. Phthalate esters are used extensively as a plasticizer for plastic manufacture such as PVC bags and medical devices. This study investigated the effects of leached components from spring water container's cap and seal film. Phthalates, e.g. dimethy1 phthalate (DMP), diethy1 phthalate (DEP), di-n-buty1 phthalate (DBP), benzy1buty1 phthalate (BBP), di-(2-ethy1hexy1) phthalate (DEHP), and bisphenol A (BPA) were measured in the spring water. The bisphenol A was not detected or below the detection limit on the leaching from cap, sealing or spring water. DEHP were detected 90-116 ppb on the leaching from seal after 2 weeks, and 0.48-0.51 ppb from the spring water after I week. BBP were measured from seal within 1 week 25.4-66 ppb and below 0.12 ppb from spring water within 2 days. DMP were detected from seal within 2 weeks 51-68.5 ppb and 0.12 ppb after 2 weeks. DEP were measured from seal within 2 weeks 48.1-141 ppb and the concentrations were increased by the time from 0.10 to 0.31 ppb at spring water. DBP were detected from the seal within 2 weeks 92.3-5100 ppb and the concentration were decreased by the time from 0.24 to 0.10 ppb at spring water. These results indicate that some phthalate esters contaminated with spring water using the intact cap and seal film. It is concluded that the measured levels of phthalates leaching from these materials might in vivo only be slightly less than 1/10 of the LOAEL.

• Journal of Life Science
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• v.26 no.10
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• pp.1153-1162
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• 2016

Termitomyces albuminosus (Berk.) Heim is a well-known wild edible mushroom in the southern region of China. Novel cerebrosides, termed termitomycesphins, isolated from EtOH extract of T. albuminosus have shown significant neuritogenic activity. Neurotrophic factors have been targeted as potential therapeutic drugs for the treatment of neurodegenerative disorders. However, before expanding their applications to include food or therapeutic agents in Korea, a safety evaluation of T. albuminosus is needed. Herein, in a repeated-dose 90-day oral toxicity study, rats were exposed to a basal diet of powder ground from dried T. albuminosus at dose levels of 5%, 2.5%, 1.25%, and 0%. The following endpoints were evaluated: clinical observation, body weight, gross and microscopic pathology, clinical chemistry, and hematology. Significant dose-dependent increases in the weight of the left kidney were observed, possibly due to the test substance. Based on toxicity-decision criteria for minor compound-related changes (no observed adverse effect level [NOAEL] and no observed effect level [NOEL]), NOAEL was observed in male rats at a dose of 5% of dried T. albuminosus powder, and NOEl was observed in female rats at the same dose. The results point to the safety and potential use of T. albuminosus as a nontoxic neurotrophic factor.

• Korean Journal of Agricultural Science
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• v.28 no.1
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• pp.33-40
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• 2001

The authors attempted to derive a comprehensive quantitative structure-toxicity relationships (QSTRs) between various physicochemical parameters of phenyl substituents in fungicidal phenylthionocarbamate derivatives and toxicity evaluated using TOPKAT calculation. On the basis of this approach we made preditions for toxicity values for not yet tested substances with respect to these systems. The results suggested that the optimal values, $(B_2)_{opt.}=1.54_{\AA}$(Ames mutagenicity), $(R)_{opt.}=0.16$ (car-cinogenicity of male rat), $(\pi)_{opt.)=0.16$ (carcinogenicity of male mouse), $({\varepsilon}LOMO)_{opt}=-0.52e.v.$ ($LD_{50}$ of rat oral), $(B_3){opt.}=1.54_{\AA}$(chronic LOAEU), $(logP)_{opt.}=4.25$ ($LC_{50}$ of Fathead minnow) and $({\sigma})_{opt}=-0.68$ ($EC_{50}$ of Daphnia magna) of phenyl substituents were strongly correlated with the acute and chronic toxicities.