• Toxicological Research
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• 제34권2호
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• pp.111-125
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• 2018

Solvents can be used in the manufacture of medicinal products provided their residual levels in the final product comply with the acceptable limits based on safety data. At worldwide level, these limits are set by the "Guideline Q3C (R6) on impurities: guideline for residual solvents" issued by the ICH. Diisopropyl ether (DIPE) is a widely used solvent but the possibility of using it in the pharmaceutical manufacture is uncertain because the ICH Q3C guideline includes it in the group of solvents for which "no adequate toxicological data on which to base a Permitted Daily Exposure (PDE) was found". We performed a risk assessment of DIPE based on available toxicological data, after carefully assessing their reliability using the Klimisch score approach. We found sufficiently reliable studies investigating subchronic, developmental, neurological toxicity and carcinogenicity in rats and genotoxicity in vitro. Recent studies also investigated a wide array of toxic effects of gasoline/DIPE mixtures as compared to gasoline alone, thus allowing identifying the effects of DIPE itself. These data allowed a comprehensive toxicological evaluation of DIPE. The main target organs of DIPE toxicity were liver and kidney. DIPE was not teratogen and had no genotoxic effects, either in vitro or in vivo. However, it appeared to increase the number of malignant tumors in rats. Therefore, DIPE could be considered as a non-genotoxic animal carcinogen and a PDE of 0.98 mg/day was calculated based on the lowest No Observed Effect Level (NOEL) value of $356mg/m^3$ (corresponding to 49 mg/kg/day) for maternal toxicity in developmental rat toxicity study. In a worst-case scenario, using an exceedingly high daily dose of 10 g/day, allowed DIPE concentration in pharmaceutical substances would be 98 ppm, which is in the range of concentration limits for ICH Q3C guideline class 2 solvents. This result might be considered for regulatory decisions.

• Fisheries and Aquatic Sciences
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• 제27권2호
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• pp.66-75
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• 2024

Heavy metals are naturally found in the ecosystem, and their presence in the freshwater river is increasing through anthropogenic activities which pose a threat to living beings. In this study, heavy metal concentrations (Zn, Mn, Cu, Cd, Cu, Cr, Pb, and Ni) in different organs (muscle, skin, and gill) of fish from the Padma River were evaluated to quantify, and compare the contamination levels and related human health risks. The results revealed that the heavy metal concentrations in the water, surface sediments, and fish taken from the Padma River were far below the WHO/USEPA's permitted limits. The estimated daily intake (EDI) value in muscle was less than the tolerable daily intake (TDI). The target hazard quotient (THQ) and hazard indexes (HI) were less than 1, showing that consumers face no non-carcinogenic risk (CR). CR values of Cu, Cd, Cr, Pb, and Ni ranged from 4.00 × 10^-8 to 6.35 × 10^-6, less than 10^-4, and total carcinogenic risk (CRt) values ranged from 9.85 × 10^-6 to 1.10 × 10^-5, indicating some pose a CR from consumption of those fish from the Padma River. To establish a more accurate risk assessment, numerous exposure routes, including inhalation and cutaneous exposure, should be explored.

• 한국축산식품학회지
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• 제40권5호
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• pp.675-688
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• 2020

Polycyclic aromatic hydrocarbons (PAHs) are dangerous chemical compounds that can be formed by cooking foods at high temperatures. The aim of this study is to determine the level of contamination of PAH compounds with high performance liquid chromatography (HPLC) on heat treated meat samples and the consumption of PAH compounds in meat samples, as well as the dietary exposure status and possible health risk estimation. In five different heat treated meat samples (meat doner, chicken doner, meatballs, grilled chicken, and fish), the total PAH (Σ16PAH) contamination level was 6.08, 4.42, 4.45, 4.91, and 7.26 ㎍/kg, respectively. Benzo[a]pyrene (BaP) in meatballs and grilled fish samples had a level 0.70 and 0.73 ㎍/kg. All of the samples analyzed were found to be below the EU permitted limit (5 ㎍/kg) in terms of BaP. Estimates of daily intake (EDI) for a total of 16PAH in heat treated meat doner, chicken doner, meatballs, grilled chicken and fish samples were 3.41, 3.71, 2.49, 4.12, and 1.77 ng/kg bw/day, respectively. In this study, the average margin of exposure (MOE) value calculated was found in the range of 179.487 and 425.000 for BaP and PAH4. This study is the first study to provide important information in terms of evaluating the possible health risk that PAH compounds can create in people's diets due to heat treatment of meat and meat products in Sivas, Turkey.

• 방사선산업학회지
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• 제5권4호
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• pp.337-345
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• 2011

In order to provide an effective preparedness for a nuclear or radiological emergency happening in the domestic or neighborhood countries and to solve the vague fear of the people for the ingestion of radioactive livestock products, the establishment of national guideline level for radionuclides in feed is urgently necessary. This is because it is important to secure the safety and to manage the crisis in the agricultural, fishery and food sector by performing the effective safety control during and after nuclear incident. This study was performed to investigate the report cases of international organizations and foreign countries to set up a domestic control standard for managing radioactive substances that may be contaminated in animal feeds due to the nuclear power plant incident. In addition, an attempt was made to provide a useful reference that can help prepare a domestic control standard, using a coefficient that can consider the transfer into livestock through the intake of radioactive contaminated animal feeds. The standard radioisotopes investigated were confined to radioactive cesium ($^{137+134}Cs$) and iodine ($^{131}I$). Guideline level for the radionuclides was calculated by using the transfer coefficient factor and the maximum daily intake of animal feed provided by IAEA. For example, the maximum daily intake of animal feed was set as $25kg\;d^{-1}$ for dairy cows, $10kg\;d^{-1}$ for beef cattle, $3.0kg\;d^{-1}$ for pigs and $0.15kg\;d^{-1}$ for chickens. The result values for radioactive cesium were calculated as $8,696Bq\;kg^{-1}$, $4,545Bq\;kg^{-1}$, $1,667Bq\;kg^{-1}$ and $2,469Bq\;kg^{-1}$, respectively. The results for radioactive iodine showed the ranges between $741Bq\;kg^{-1}$ and $76,628Bq\;kg^{-1}$. These data can be utilized as a scientific reference for the preparation of a crisis management manual for the emergency control due to nuclear power plant accident in Korea and neighboring country. These results will contribute to establish the safe feed management system at national level as manual for responding the radioactive exposure of agricultural products and animal feeds, which are currently not established.

• 한국식품위생안전성학회지
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• 제26권4호
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• pp.315-321
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• 2011

아플라톡신은 Aspergillus flavus와 A. parasiticus.에 의해 생성되는 독소대사산물로 강력한 발암성물질로서 땅콩, 옥수수, 쌀, 보리 등 탄수화물이 주성분인 곡류가 그 기질로 알려져 있으며 생약에서도 검출된 보고가 있다. 본 연구는 아플라톡신($B_1$, $B_2$, $G_1$, $G_2$) 모니터링을 통해 생약의 곰팡이 독소 허용 기준 마련을 위한 기초 자료로 활용하고자 한다. 모니터링을 위해 국내(5개 지역)와 중국(2개 지역)에서 유통 중인 생약 50품목의 558시료를 수거하였다. 수거한 시료는 관능검사를 거쳐 적합한 시료를 선정하여 실험에 사용하였다. 아플라톡신 분석은 시료를 70% 메탄올로 추출하여 면역친화성 칼럼으로 정제한 후, 칼럼 후 유도체화 장치(PHRED)가 장착된 HPLC-FLD로 분석하였다. 아플라톡신 분석을 위해 시험법을 검증하였다. 그 결과 검출한계와 정량한계는 각각 $0.0l5{\sim}0.138\;{\mu}g/kg$, $0.046{\sim}0.418\;{\mu}g/kg$였으며 회수율은 67.4~96.2%로 나타났다. 검증된 시험법으로 국내와 중국에서 유통 중인 생약을 대상으로 모니터링한 결과, 생약 2건(보두, 호미카)에서 아플라톡신($B_1$, $G_1$)이 검출되었다. 보두에서는 아플라톡신 $B_1$이 1.7 ${\mu}g/kg$, $G_1$이 0.9 ${\mu}g/kg$이 검출되었고, 호미카에서는 $G_1$이 0.8 ${\mu}g/kg$ 검출되었다. 또한 생약의 주복용 형태인 탕액으로 조제 하였을 때, 아플라톡신의 이행정도를 알아보고자 생약에 아플라톡신을 오염시키고 무 압력과 압력 조건에서 열수 추출 하였다. 탕액 조제시 아플라톡신의 이행률은 무압력 조건에서 13.6~51.3%였다.