• Toxicological Research
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• 제27권3호
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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.

• 대한환경공학회지
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• 제33권1호
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• pp.60-70
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• 2011

본고에서는 현재 시행중인 해양오염퇴적물질 관리용 유해화학물질 정화지수($CI_{HC}$)를 대상으로, $CI_{HC}$은 동일하나 유해 물질별 함량이 다른 해저퇴적물들이 같은 생물위험을 보이는가를 판단하려 하였다. 이를 위해 5개의 가상 오염퇴적물을 설정하고, 퇴적물 위험평가를 위한 트로픽트레이스 모형($TrophicTrace^{(R)}$ model)을 이용하여, 이 가상 퇴적물이 쥐노래미(Hexagrammos otakii)에 대해 미치는 생물위험을 최대무작용량에 기반한 독성지수(NOAEL TQ)와 최소작용량에 기반한 독성지수(LOAEL TQ)로 평가하였다. 쥐노래미에 대한 NOAEL TQ의 합계는 5개 가상 오염퇴적물에서 0.69~1.54의 범위였고, LOAEL TQ의 합계는 0.111~0.261로 약 2배 이상의 차이가 났다. 이는 퇴적물 유해물질 환경기준이 해양저서무척추동물군집에 대한 영향만을 고려하고 사람으로 연결되는 식용의 쥐노래미에 대한 영향을 반영하지 않기 때문으로 사료된다. 인체에 대한 비발암위험지수(HI) 값은 PCB의 경우 9.8~47.1로 매우 위험한 것으로 나타났다. PCB의 발암위험도는 5개 퇴적물에서 $39{\sim}190{\times}10^{-5}$으로 높게 나타났으며 As의 경우에도 $8.1{\sim}18.0{\times}10^{-5}$으로 높게 나타났다. 유해화학물질정화지수가 8로 동일한 5개 가상 오염퇴적물에서 비발암위험지수(HI) 및 발암위험도가 서로 매우 다르게 나타난 것은 각 오염물질별로 인체에 악영향을 미치는 정도가 다르기 때문이다.

• 한국산업보건학회지
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• 제22권3호
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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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• 제18권1호
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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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• 제31권4호
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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.

• 한국환경보건학회지
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• 제31권6호
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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.

• 생명과학회지
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• 제26권10호
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• pp.1153-1162
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• 2016

계종버섯(Thermitomyces albuminosus)의 안정성을 입증하기 위하여 사료에 계종버섯의 분말을 5%, 2.5%, 1.25%, 0%를 혼합하여 90일 동안 랫드에 자유 급이 시켜 실험동물의 일반증상, 체중변화, 혈액학적 검사, 부검소견, 임상병리, 조직병리학적 검사의 결과를 토대로 독성을 평가하였다. 독성판정기준은 독성의 정도와 양상에 따라 weight-based classification (독성 강도에 따른 분류)로 분류 하였는데 비시험물질-유래 변화인 NOEL, 시험물질-유래 경미한 변화는 NOAEL, 시험물질-유래 중요한 변화는 LOAEL을 기준으로 나누었다. 시험결과, 수컷 좌, 우측 신장 중량이 용량의존적으로 증가하여 고용량군에서는 12%, 8% 증가 하였다. 하지만 임상, 조직병리학적 결과 독성으로 판단되는 소견이 관찰되지 않아 시험물질-유래 경미한 변화로 판단으로 분류하였다. 따라서 판정기준에 따라 수컷은 NOAEL 암컷은 NOEL이 식이함량 5%로 추정되지만 식약처고시에 따라 암수 모두 NOAEL이 식이함량의 5%로 추정할 수 있다. 따라서 계종버섯은 식품 또는 기능성식품으로의 개발에 문제가 없을 것으로 사료된다.

• 농업과학연구
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• 제28권1호
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• pp.33-40
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• 2001

아직까지 시도된 바 없는 살균성 phenylthionocarbamate 유도체들의 phenyl-치환기가 변화함에 따라 TOPKAT 계산으로 예측된 다양한 급성 및 만성 독성값에 미치는 정량적인 분자구조와 독성과의 관계 (QSTRs)를 검토한 결과는 다음과 같다. (1) 기질분자의 구조변화에 따른 독성치와 그의 판별점수 (D.S.) 에 기초하여 분자 중 특정부분 (fragment)이 양 (+)의 값으로 독성에 기여하는 대체적인 순서는 Aro. C=C, -O-, -NH- 및 할로겐 (X) 원자의 순이었다. (2) 대부분의 화합물들은 매우 높은 돌연변이와 발암성이 예측되었으며 특히, 치환기의 위치에 관계없이 fluoro-치환체는 $B_2$상수에 따른 입체효과 ($(B_2)_{opt.}=1.54{\AA}$)에 의하여 모두 100% 돌연변이를 발현한 반면에 trifluorornethyl-치환체는 돌연변이 발현 가능성이 전혀 없었다. (3) 가장 높은 독성 발현조건은 phenyl-치환기에 대한 소정의 적정값으로 돌연변이성에는 $(B_2)_{opt.}=1.54{\AA}$, 발암성에서 수컷 rat와 mouse는$(R)_{opt.}=0.16$ 및 $(\pi)_{opt.}=0.16$ 그리고 rat의 경구독성은 $LD_{50};({\varepsilon}LOMO)_{opt}=-0.52e.v.$, chronic LOAEL; $(B_3){opt.}=1.54{\AA}$, 어독성은 ${LC_50}$; $(logP)_{opt.}=4.25$ 및 물벼룩에 대한 독성은 $EC_{50};({\sigma})_{opt}=-0.68$를 나타내는 경우 이었다. (4) 돌연변이성에는 할로겐 중, fluoro-기를 위시하여 nitro 및 methyl-기 등의 순서로 기여하였고 phenyl 고리 상, 치환기의 위치와 전자 수수관계에는 대체로 무관한 경향을 나타내었다.