• Toxicological Research
• /
• 제33권4호
• /
• pp.291-297
• /
• 2017

This study was performed to investigate the dose-response relationship between average daily cadmium dose (ADCD) from rice and the occurrence of urinary cadmium (U-Cd) in individuals eating that rice. This was a retrospective cohort designed to compare populations from two areas with different levels of cadmium contamination. Five-hundred and sixty-seven participants aged 18 years or older were interviewed to estimate their rice intake, and were assessed for U-Cd. The sources of consumed rice were sampled for cadmium measurement, from which the ADCD was estimated. Binary logistic regression was used to examine the association between ADCD and U-Cd (cut-off point at $2{\mu}g/g$ creatinine), and a correlation between them was established. The lowest estimate was $ADCD=0.5{\mu}g/kg\;bw/day$ [odds ratio (OR) = 1.71; with a 95% confidence interval (CI) 1.02-2.87]. For comparison, the relationship in the contaminated area is expressed by $ADCD=0.7{\mu}g/kg\;bw/day$, OR = 1.84; [95 % CI, 1.06-3.19], while no relationship was found in the non-contaminated area, meaning that the highest level at which this relationship does not exist is $ADCD=0.6{\mu}g/kg\;bw/day$ [95% CI, 0.99-2.95]. Rice, as a main staple food, is the most likely source of dietary cadmium. Abstaining from or limiting rice consumption, therefore, will increase the likelihood of maintaining U-Cd within the normal range. As the recommended maximum ADCD is not to exceed $0.6{\mu}g/kg\;bw/day$, the consumption of rice grown in cadmium-contaminated areas should not be more than 246.8 g/day. However, the exclusion of many edible plants grown in the contaminated area from the analysis might result in an estimated ADCD that does not reflect the true level of cadmium exposure among local people.

• Toxicological Research
• /
• 제35권1호
• /
• pp.75-81
• /
• 2019

Tartrazine (TAZ) is one of the most commonly used artificial dyes for foods and drugs. We determined the effect of TAZ on fetal development by examining morphological, visceral, and skeletal malformations in rat fetuses following daily oral administration of TAZ to pregnant Wistar rats at the 6th-15th day of gestation. TAZ at 0.45 and 4.5 mg/kg induced 6.0 and 7.1% fetal resorptions, as well as 10.0 and 10.5% fetal mortality, respectively. Fetal body weight and length were significantly lower in the groups treated with TAZ at 0.45 ($3.97{\pm}0.21g$ and $27.3{\pm}0.54mm$, respectively) and 4.5 mg/kg ($3.48{\pm}0.15g$ and $23.22{\pm}1.02mm$, respectively) than in the control group ($4.0{\pm}0.15g$ and $30.01{\pm}0.42mm$, respectively). TAZ at 0.45 and 4.5 mg/kg induced hepatic damage (20 and 33.3%, respectively), dark brown pigmentation due to hemosiderin in the splenic parenchyma (16.7 and 21.7%, respectively), as well as destructed and necrotic renal tubules (16.7 and 26.7%, respectively) in the fetuses. Moreover, TAZ at 0.45 and 4.5 mg/kg caused one or more missing coccygeal vertebrae (20 and 40%, respectively), missing sternebrae (6 and 10%, respectively), missing hind limbs (24 and 4%, respectively), and irregular ribs (16 and 20, respectively) in the fetuses. We concluded that TAZ has embryotoxic and teratogenic potentials in rats.

• Toxicological Research
• /
• 제14권4호
• /
• pp.547-555
• /
• 1998

The subchronic toxicity of a combined preparation of ticlopidine and ginkgo biloba extract (EGb 761) mixed in a ratio of 10: 4 was examined in male and female Sprague-Dawley rats. Rats were treated with the test substance at a dose of 52 mg/kg, 156 mg/kg, or 467 mg/kg intragastrically for 30 consecutive days. Control rats were treated with vehicle only. Each group consisted of 10 rats. No death or abnormal clinical signs were observed throughout the administration period. A transient decrease in body weight gain and food intake was observed in the rats treated with the high dose (467 mg/kg), which was recovered to normal in a week. There were no drug-related differences in urinalysis and hematological results. A significant increase in serum total cholesterol and total protein was observed in both sexes of the rats treated with a dose of 467 mg/kg daily, but all the other values obtained in serum chemistry appeared to be within normal range. A dose dependent increase in liver weight was observed in both male and female rats. Relative kidney weight was also increased in the high dose groups. There was no gross pathological finding at terminal sacrifice. Microscopic histopathological examination did not show any lesion in terms of correlation with administration of the test substance. The results suggest that under the conditions employed in this study no observable effect level (NOEL) of the test substance be 52 mg/kg/day.

• Toxicological Research
• /
• 제16권4호
• /
• pp.293-301
• /
• 2000

Toxicity of a combined preparation of ticlopidine and ginkgo biloba extract (EGb 761) in a ratio of 10: 4 was examined in male and female Sprague-Dawley rats. Rats were treated with the test substance intragastrically at a dose of 0 mg/kg, 17 mg/kg, 52 mg/kg or 156 mg/kg for 91 consecutive days. No death or abnormal clinical sign was observed throughout the administration period. There was no difference in body weight gain, food intake or water consumption among different dose groups. Test sub-stance-related differences were not observed in urinalysis. In hematological results mean corpuscular hemoglobin (MCH) of low and high dose male group was increased. Prothrombin time of medium and high dose female group was decreased. A significant increase in serum total cholesterol was observed in both sexes of rats treated with a daily dose of 156 mg/kg, but all the other values obtained in serum chemistry appeared to be within normal ranges. A dose dependent increase in the relative liver and kidney weights was observed in both male and female rats. There were no gross pathological findings at terminal sacrifice. Microscopic histopathological examination did not show any lesion associated with administration of the test substance. The results suggest that under the conditions employed in this study no observable effect level (NOEL) of the test substance be greater than 17 mg/kg/day, but less than 52 mg/kg/day.

• Toxicological Research
• /
• 제32권3호
• /
• pp.195-205
• /
• 2016

This study was performed to select single nucleotide polymorphisms (SNPs) related to the body burden of heavy metals in Koreans, to provide Korean allele frequencies of selected SNPs, and to assess the difference in allele frequencies with other ethnicities. The candidate-gene approach method and genome-wide association screening were used to select SNPs related to the body burden of heavy metals. Genotyping analysis of the final 192 SNPs selected was performed on 1,483 subjects using the VeraCode Goldengate assay. Allele frequencies differences and genetic differentiations between the Korean population and Chinese (CHB), Japanese (JPT), Caucasian (CEU), and African (YIR) populations were tested by Fisher's exact test and fixation index ($F_{ST}$), respectively. The Korean population was genetically similar to the CHB and JPT populations ($F_{ST}$ < 0.05, for all SNPs in both populations). However, a significant difference in the allele frequencies between the Korean and CEU and YIR populations were observed in 99 SNPs (60.7%) and 120 SNPs (73.6%), respectively. Ten (6.1%) and 26 (16.0%) SNPs had genetic differentiation ($F_{ST}$ > 0.05) among the Korean-CEU and Korean-YIR comparisons, respectively. The SNP with the largest $F_{ST}$ value between the Korean and African populations was cystathionine-${\beta}$-synthase rs234709 ($F_{ST}$: KOR-YIR, 0.309; KOR-CEU, 0.064). Our study suggests that interethnic differences exist in SNPs associated with heavy metals of Koreans, and it should be considered in future studies that address ethnic differences in heavy-metal concentrations in the body and genetic susceptibility to the body burden of heavy metals.

• Applied Biological Chemistry
• /
• 제47권1호
• /
• pp.61-66
• /
• 2004

신선찰거대배아미, 화청거대배아미 및 남풍거대배아미 등 거대배 돌연변이 계통 쌀 3종류 및 일반미의 70% 에탄올 추출물을 제조하여, 이들의 항산화 활성 및 항변이원성을 비교 검정하였다. 거대배아미 추출물의 항산화 활성은 DPPH radical 및 Fenton 반응에 의해서 유도되는 hydroxy radical의 소거활성, hypoxanthine/xanthine oxidase system에서 생성되는 활성산소종인 superoxide radical의 소거활성, linoleic acid자동산화에 대한 지질 과산화 억제활성 및 토끼 적혈구 막지질의 과산화 억제활성 둥으로써 검정하였으며, 항변이원성은 E. coli PQ 37 균주를 사용하여 화학적 변이원 mitomycin C에 대한 변이원성 억제효과를 SOS chromotest에 의해서 검정하였다. 일반미 품종에 비해서 거대배아미 품종의 항산화 활성 및 항변이원성이 모두 높았으며, 거대배아미 품종 중에서는 남풍거대배아미가 가장 효과적인 경향이 있었다. 남풍거대배아미의 DPPH radical, superoxide radical과 hydroxyl radical 소거활성, 그리고 지질과산화 억제활성은 일반미보다 각각 2.3배, 3.3배, 1.7배 및 2.5배 정도까지 더 높았다.

• Toxicological Research
• /
• 제24권1호
• /
• pp.37-44
• /
• 2008

The in vitro cell transformation assays (CTA) were performed using BALB/3T3 murine fibroblasts and HaCaT human keratinocytes in order to evaluate concordance between both in vitro CTAs and carcinogenicity with compounds differing in their genotoxic and carcinogenic potential. Six test articles were evaluated, two each from three classes of compounds: genotoxic carcinogens (2-amino-5-nitrophenol and 4-nitroquinoline-N-oxide), genotoxic noncarcinogens (8-hydroxyquinoline and benzyl alcohol), and nongenotoxic carcinogens (methyl carbamate and N-nitrosodiphenylamine). Any foci of size $\geq$2 mm regardless of invasiveness and piling was scored as positive in CTA with BALB/3T3. As expected, four carcinogens regardless of their genotoxicity had positive outcomes in two-stage CTA using BALB/3T3 cells. However, of the two genotoxic noncarcinogens, benzyl alcohol was positive CTA finding. We concluded that, of the 6 chemicals tested, the sensitivity for BALB/3T3 system was reasonably high, being 100%. The respective specificity for BALB/3T3 assay was 50%. We also investigated the correlation between results of BALB/3T3 assay and results from HaCaT assay in order to develop a reliable human cell transformation assay. However, evaluation of staining at later time points beyond the confluency stage did not yield further assessable data because most of HaCaT cells were detached after $2{\sim}3$ days of confluency. Thus, after test article treatment, HaCaT cells were split before massive cell death began. In this modified protocol for this HaCaT system, growing attached colonies were counted instead of transformed foci 3 weeks since last subculture. Compared to BALB/3T3 assay, HaCaT assay showed moderate low sensitivity and high specificity. Despite these differences in specificity and sensitivity, both cell systems did exhibit same good concordance between in vitro CTA and rodent carcinogenicity findings (overall 83% concordant results). At present the major weakness of these in vitro CTA is lack of validation for regulatory acceptance and use. Thus, more controlled studies will be needed in order to be better able to assess and quantitatively estimate in vitro CTA data.

• 미생물학회지
• /
• 제49권3호
• /
• pp.253-261
• /
• 2013

본 연구에서는 숙성된 된장으로부터 분리된 유산균에 의한 aflatoxin $B_1$의 결합 정도를 배양조건에 따라 측정하였고, 물리화학적 처리조건이 aflatoxin $B_1$에 대한 유산균 세포의 결합력에 미치는 영향을 살펴보았다. Enterococcus faecium DJ22, Lactobacillus fermentum DJ35, Lactobacillus rhamnosus DJ42 및 Lactobacillus pentosus DJ47는 19.3-52.1% 정도의 aflatoxin $B_1$ 결합 효과를 나타내어 균종에 따라 결합력에 차이가 있었다. 하지만 E. faecalis DJ14, Lactobacillus panis DJ29 및 Pediococcus halophilus DJ50 균주는 aflatoxin $B_1$에 대한 결합력을 나타내지 않았다. Aflatoxin $B_1$에 대한 유산균의 결합력과 결합속도는 독소의 농도, 반응시간 및 온도와 초기 세포수 등의 배양 조건에 따라 유의한 차이가 있었다. Aflatoxin $B_1$의 결합력은 세척 횟수에 따라 현저하게 감소하였고, 감소율은 살아있는 세포와 가열 처리한 세포에서 비슷하게 나타났다. 가열, 산성 pH, ${\alpha}$-amylase, protease, lysozyme 혹은 sodium metaperiodate의 처리에 의해 결합력이 유의하게 감소된 것으로 보아 주로 세포벽에 존재하는 당이나 단백질에 aflatoxin $B_1$이 결합되며, urea의 처리에 의해 결합력에 낮아지는 것은 이들 사이에는 소수성 결합이 작용하는 것으로 추정되었다.

• Toxicological Research
• /
• 제25권3호
• /
• pp.140-146
• /
• 2009

This study was performed to evaluate the toxicity of cadmium selenide for a period of 28 days in Sprague-Dawley rats. Each of 10 healthy male and females rats per group received daily oral administration for 28-day period at dosage levels 30, 300 and 1,000 mg/kg of body weight. Mortality and clinical signs were checked, and body weight, water intake and food consumption were also recorded weekly. There were no dose-related changes in food consumption or urine volume. All animals survived to the end of study with no clinical signs or differences in body weight gain observed when compared with the control group. At the end of study, all animals including control group, were subjected to necropsy. Blood samples were collected for hematology tests including coagulation time and biochemistry analysis. Blood coagulation time and relative organ weight were unaffected by all received doses. White Blood Cell (WBC) counts significantly increased in the 300 mg/kg administered male animal group when compared to the control. Monocyte (MO) value were also increased significantly in both 300 and 1,000 mg/kg male animal group. However, Mean Corpuscular Volume (MCV) were significantly decreased compared with the control in the 1,000 mg/kg dose groups for male and female animals. Mean Corpuscular Hemoglobin (MCH) decreased significantly for female in the 300 and 1,000 mg/kg group compared to the control. Blood biochemical values of Inorganic phosphorus (IP) were significantly increased in both the 300 and 1,000 mg/kg dose groups in male animals when compared to the control. Creatinine (CRE) levels indicated significant increase in kidney function for the female, 30 mg/kg dose group when compared with control. There was a significant decrease in thymus absolute organ weight in the female, 1,000 mg/kg dose group when compared with control. Histopathological findings revealed no evidence of injury related to cadmium selenide except for one case of focal hepatic inflammation in the high dose (1,000 mg/kg) group. One case of lung inflammation was also seen in the control group. Basis on these result, the No Observable Adverse Effect Level (NOAEL) of cadmium selenide was determined to be more than 1,000 mg/kg/day for male and female rats under conditions in this study.

• Toxicological Research
• /
• 제31권3호
• /
• pp.255-264
• /
• 2015

Heterocyclic amines (HCAs) and acrylamide are unintended hazardous substances generated by heating or processing of foods and are known as carcinogenic and mutagenic agents by the animal experiments. A simple method was established for a rapid and accurate determination of 12 types of HCAs (IQ, MeIQ, Glu-P-1, Glu-P-2, MeIQx, Trp-P-1, Trp-P-2, PhIP, $A{\alpha}C$, $MeA{\alpha}C$, Harman and Norharman) and acrylamide in three food matrices (non-fat liquid, non-fat solid and fat solid) by isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS). In every sample, a mixture of internal standards including $IQ-d_3$, $MeIQx-d_3$, $PhIP-d_3$, $Trp-P-2-^{13}C_2-^{15}N$ and $MeA{\alpha}C-d_3$ was spiked for quantification of HCAs and $^{13}C_3$-acrylamide was also spiked for the analysis of acrylamide. HCAs and acrylamide in sample were extracted with acetonitrile and water, respectively, and then two solid-phase extraction cartridges, ChemElut: HLB for HCAs and Accucat: HLB for acrylamide, were used for efficiently removing interferences such as pigment, lipid, polar, nonpolar and ionic compounds. Established method was validated in terms of recovery, accuracy, precision, limit of detection, limit of quantitation, and linearity. This method showed good precision (RSD < 20%), accuracy (71.8~119.1%) and recovery (66.0~118.9%). The detection limits were < 3.1 ng/g for all analytes. The correlation coefficients for all the HCAs and acrylamide were > 0.995, showing excellent linearity. These methods for the detection of HCAs and acrylamide by LC-MS/MS were applied to real samples and were successfully used for quantitative monitoring in the total diet study and this can be applied to risk assessment in various food matrices.