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benchmark dose Assessment for Coke Oven Emissions-Induced Mitochondrial DNA Copy Number Damage Effects

Biomedical and Environmental Sciences 2023年第6期36卷 490-500页

作者： YAN Zhao Fan GU Zhi Guang FAN Ya Hui LI Xin Ling NIU Ze Ming DUAN Xiao Ran Mallah Ali Manthar ZHANG Qiao YANG Yong Li YAO Wu WANG Wei Department of Occupational Health and Occupational Diseases College of Public HealthZhengzhou UniversityZhengzhou 450001HenanChina Department of Toxicology College of Public HealthZhengzhou UniversityZhengzhou 450001HenanChina Department of Epidemiology and Biostatistics College of Public HealthZhengzhou UniversityZhengzhou 450001HenanChina

Objective The study aimed to estimate the benchmark dose(BMD)of coke oven emissions(COEs)exposure based on mitochondrial damage with the mitochondrial DNA copy number(mtDNAcn)as a *** A total of 782 subjects were recruited,including 238 controls and 544 exposed *** mtDNAcn of peripheral leukocytes was detected through the real-time fluorescence-based quantitative polymerase chain *** BMD approaches were used to calculate the BMD of COEs exposure based on the mitochondrial damage and its 95%confidence lower limit(BMDL).Results The mtDNAcn of the exposure group was lower than that of the control group(0.60±0.29 vs.1.03±0.31;Pdose-response relationship was shown between the mtDNAcn damage and *** the benchmark dose Software,the occupational exposure limits(OELs)for COEs exposure in males was 0.00190 mg/m^(3).The OELs for COEs exposure using the BBMD were 0.00170 mg/m^(3)for the total population,0.00158 mg/m^(3)for males,and 0.00174 mg/m^(3)for *** possible risk obtained from animal studies(PROAST),the OELs of the total population,males,and females were 0.00184,0.00178,and 0.00192 mg/m^(3),*** Based on our conservative estimate,the BMDL of mitochondrial damage caused by COEs is0.002 mg/m^(3).This value will provide a benchmark for determining possible OELs.

关键词： Coke oven emissions Mitochondrial DNA copy number benchmark dose Occupational exposure limits

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Application of benchmark dose (BMD) in Estimating Biological Exposure Limit (BEL) to Cadmium

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Biomedical and Environmental Sciences 2007年第6期20卷 460-464页

作者： Bo SHAO TAI-YI JIN XUN-WEI WU QING-HU KONG TING-TING YE Department of Occupational Health and Toxicology School of Public Health Fudan University Shanghai 200032 China Institute of Environmental Health Zhejiang Academy of Medical Sciences Hangzhou 310013 ZheJiang China

Objective To estimate the biological exposure limit （BEL） using benchmark dose （BMD） based on two sets of data from occupational epidemiology. Methods Cadmium-exposed workers were selected from a cadmium smelting factory and a zinc product factory. Doctors, nurses or shop assistants living in the same area served as a control group. Urinary cadmium （UCd） was used as an exposure biomarker and urinary D2-microgloburin （B2M）, N-acetyl-D-D-glucosaminidase （NAG） and albumin （ALB） as effect biomarkers. All urine parameters were adjusted by urinary creatinine. Software of BMDS （Version 1.3.2, EPA.U.S.A） was used to calculate BMD. Results The cut-off point （abnormal values） was determined based on the upper limit of 95% of effect biomarkers in control group. There was a significant dose response relationship between the effect biomarkers （urinary B2M, NAG9 and ALB） and exposure biomarker （UCd）. BEL value was 5 μg/g creatinine for UB2M as an effect biomarker, consistent with the recommendation of WHO. BEL could be estimated by using the method of BMD. BEL value was 3 μg/g creafinine for UNAG as an effect biomarker. The more sensitive the used biomarker is, the more occupational population will be protected. Conclusion BMD can be used in estimating the biological exposure limit （BEL）. UNAG is a sensitive biomarker for estimating BEL after cadmium exposure.

关键词： benchmark dose Biological exposure limit Biomarker

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Subchronic Oral Toxicity Evaluation of Sodium Dehydroacetate: A 90-day Repeated dose Study in Rats

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Biomedical and Environmental Sciences 2022年第4期35卷 296-311页

作者： FANG Jin LIU Hai Bo ZHI Yuan FENG Yong Quan WANG Hui Ling CUI Wen Ming ZHANG Ji Yue WANG Hua Li YU Zhou JIA Xu Dong NHC Key Laboratory of Food Safety Risk Assessment Chinese Academy of Medical Science Research Unit(2019RU014)China National Center for Food Safety Risk AssessmentBeijing 100021China

Objective The present study was undertaken to evaluate the subchronic oral toxicity of sodium dehydroacetate(DHA-Na)and to determine the point of departure(POD),which is a critical factor in the establishment of an acceptable dietary *** DHA-Na was administered once daily by gavage to Sprague–Dawley rats at dose levels of 0.0,31.0,62.0,and 124.0 mg/kg BW per day for 90 days,followed by a recovery period of 4 weeks in the control and 124.0 mg/kg BW per day *** outcome parameters were mortality,clinical observations,body weights,food consumption,hematology and clinical biochemistry,endocrine hormone levels,and ophthalmic,urinary,and histopathologic *** benchmark dose(BMD)approach was applied to estimate the *** Significant decreases were found in the 62.0 and 124.0 mg/kg BW groups in terms of the body weight and food utilization rate,whereas a significant increase was found in the thyroid stimulating hormone levels of the 124.0 mg/kg BW ***,the 95%lower confidence limit on the BMD of 51.7 mg/kg BW was modeled for a reduction in body *** The repeated-dose study indicated the slight systemic toxicity of DHA-Na at certain levels(62.0 and 124.0 mg/kg BW)after a 90-day oral exposure.

关键词： Sodium dehydroacetate Sub-chronic toxicity 90-day repeated oral dose test benchmark dose Point of departure

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Subchronic Oral Toxicity Evaluation of Lanthanum： A 90-day, Repeated dose Study in Rats

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Biomedical and Environmental Sciences 2018年第5期31卷 363-375页

作者： FANG Hai Qin YU Zhou ZHI Yuan FANG Jin LIChen Xi WANG Yi Mei PENG Shuang Qing JIA Xu Dongl Key Laboratory of Food Safety Risk Assessment of Ministry of Health China National Center for Food Safety Risk AssessmentBeijing 100021China Evaluation and Research Centre for Toxicology Institute of Disease Control and PreventionAcademy of Military Medical SciencesBeijing 100071China

Objective The present study was undertaken to evaluate the subchronic toxicity of lanthanum and to determine the no observed adverse effect level（NOAEL）,which is a critical factor in the establishment of an acceptable dietary intake（ADI）.Methods In accordance with the Organization for Economic Co-operation and Development（OECD） testing guidelines,lanthanum nitrate was administered once daily by gavage to Sprague-Dawley（SD） rats at dose levels of 0,1.5,6.0,24.0,and 144.0 mg/kg body weight（BW） per day for 90 days,followed by a recovery period of 4 weeks in the 144.0 mg/kg BW per day and normal control *** parameters were mortality,clinical symptoms,body and organ weights,serum chemistry,and food consumption,as well as ophthalmic,urinary,hematologic,and histopathologic *** benchmark dose（BMD） approach was applied to estimate a point of departure for the hazard risk assessment of *** Significant decreases were found in the 144.0 mg/kg BW group in the growth index,including body weight,organ weights,and food *** study suggests that the NOAEL of lanthanum nitrate is 24.0 mg/kg BW per ***,the 95% lower confidence value of the benchmark dose（BMDL） was estimated as 9.4 mg/kg BW per day in females and 19.3 mg/kg BW per day in *** The present subchronic oral exposure toxicity study may provide scientific data for the risk assessment of lanthanum and other rare earth elements（REEs）.

关键词： Lanthanum Subchronic toxicity 90-day repeated oral dose test No observed adverse effectLevel Acceptable dietary intake benchmark dose

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Urinary Cadmium in Relation to Bone Damage: cadmium exposure threshold dose and health-based guidance value estimation

Urinary Cadmium in Relation to Bone Damage: cadmium exposure...

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中国营养学会第十五届全国营养科学大会

作者： Ying Qing College of Medical Technology Shanghai University of Medicine & Health Sciences

Cadmium(Cd) is an important hazardous environmental pollutant, which mainly targets at kidney and bone. European Food Safety Authority(EFSA) has established the dietary Cd exposure limit in 2009. Because the research on kidney injury biomarkers were sufficient and bone injury biomarkers were limited at that time, EFSA selected Beta-Microglobulin(β-MG) as the key effect biomarker to derive the standard. However, the dose-effect relationship between bone damage and urinary Cd(U-Cd), as well as the establishment of the corresponding dietary Cd exposure health-based guidance value(HBGV), are also worthy for discussion. This study retrieved worldwide epidemiological studies related to U-Cd and bone MD and conducted a systematic meta-analysis to explore the association between Cd exposure and bone damage. Methods This study searched the databases(PubMed, Web of Science, and Medline) on the correlation between the U-Cd and bone MD(Published time: 1980-2020). The T test was used to compare the data between different subgroups, a spearman correlation analysis was performed on the effect biomarkers and covariate factors. Multiple linear regression model was used to determine the correlation between U-Cd and bone MD. Considering the study-to-study heterogeneities, a random effect model was used to establish the relationship between U-Cd and bone MD and explore the influence of covariate factors. The benchmark dose(BMD) method was used to calculate the safety threshold dose of U-Cd when the bone MD changes within an acceptable range. Toxicokinetic(TK) model was used to estimate the HBGV of dietary Cd exposure of the population based on the BMDL of U-Cd. Results A total of 21 studies, containing 89 data sets, were included in this study. The average U-Cd and bone MD of the population were 2.06 μg/g Cr and 0.74 g/cm, respectively. There were significant correlations between U-Cd, bone MD and covariates(race, age, gender, body mass index(BMI)). Bone MD had a significant negative c

关键词： Cadmium bone mineral density benchmark dose toxicokinetic model health-based guidance value

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Emerging frontier technologies for food safety analysis and risk assessment

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Journal of Integrative Agriculture 2015年第11期14卷 2231-2242页

作者： DONG Yi-yang LIU Jia-hui WANG Sai CHEN Qi-long GUO Tian-yang ZHANG Li-ya JIN Yong SU Hai-jia TAN Tian-wei Beijing Key Laboratory of Bioprocess College of Life Science and TechnologyBeijing University of Chemical Technology Institute of Food Safety Chinese Academy of Inspection and Quarantine

Access to security and safe food is a basic human necessity and essential for a sustainable world. To perform hi-end rood safety analysis and risk assessment with state of the art technologies is of utmost importance thereof. With applications as exemplified by microfiuidic immunoassay, aptasensor, direct analysis in real time, high resolution mass spectrometry, benchmark dose and chemical specific adjustment factor, this review presents frontier food safety analysis and risk assessment technologies, from which both food quality and public health will benefit undoubtedly in a foreseeable future.

关键词： food safety microfluidic immunoassay aptasensor direct analysis in real time high resolution mass spectrometry benchmark dose chemical specific adjustment factor

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Aristolochic Acid-Induced Genotoxicity and Toxicogenomic Changes in Rodents

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World Journal of Traditional Chinese Medicine 2020年第1期6卷 12-25页

作者： Xi-Lin Li Xiao-Qing Guo Hai-Rong Wang Tao Chen Nan Mei Division of Genetic and Molecular Toxicology National Center for Toxicological ResearchJeffersonARUSA Tianjin Center for New Drug Safety Assessment and Research TianjinChina

Aristolochic acid(AA)is a group of structurally related nitrophenanthrene carboxylic acids found in many plants that are widely used by many cultures as traditional herbal *** is a causative agent for Chinese herbs nephropathy,a term replaced later by AA *** indicates that AA is nephrotoxic,genotoxic,and carcinogenic in humans;and it also induces tumors in the forestomach,kidney,renal pelvis,urinary bladder,and lung of rats and ***,plants containing AA have been classified as carcinogenic to humans(Group 1)bytheInternational *** our laboratories,we have conducted a series of genotoxicity and toxicogenomic studies in the rats exposed to AA of 0.1–10 mg/kg for 12 *** results demonstrated that AA treatments induced DNA adducts and mutations in the kidney,liver,and spleen of rats,as well as significant alteration of gene expression in both its target and nontarget *** treatments altered mutagenesis-or carcinogenesis-related microRNA expression in rat kidney and resulted in significant changes in protein expression *** also applied benchmark dose(BMD)modeling to the 3-month AA-induced genotoxicity *** obtained BMDL10(the lower 95%confidence interval of the BMD10 that is a 10%increase over the background level)for AA-induced mutations in the kidney of rats was about 7μg/kg body weight per *** review constitutes an overview of our investigations on AA-induced genotoxicity and toxicogenomic changes including gene expression,microRNA expression,and proteomics;and presents updated information focused on AA-induced genotoxicity in rodents.

关键词： Aristolochic acid benchmark dose genotoxicity mutation toxicogenomics

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