1.Di(2-ethylhexyl) phthalate-induced toxicity and peroxisome proliferator-activated receptor alpha: a review.
Yuki ITO ; Michihiro KAMIJIMA ; Tamie NAKAJIMA
Environmental Health and Preventive Medicine 2019;24(1):47-47
The plasticizer di(2-ethylhexyl) phthalate (DEHP) has been widely used in the manufacture of polyvinyl chloride-containing products such as medical and consumer goods. Humans can easily be exposed to it because DEHP is ubiquitous in the environment. Recent research on the adverse effects of DEHP has focused on reproductive and developmental toxicity in rodents and/or humans. DEHP is a representative of the peroxisome proliferators. Therefore, peroxisome proliferator-activated receptor alpha (PPARα)-dependent pathways are the expected mode of action of several kinds of DEHP-induced toxicities. In this review, we summarize DEHP kinetics and its mechanisms of carcinogenicity and reproductive and developmental toxicity in relation to PPARα. Additionally, we give an overview of the impacts of science policy on exposure sources.
Animals
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Diethylhexyl Phthalate
;
toxicity
;
Environmental Pollutants
;
toxicity
;
Haplorhini
;
Humans
;
Mice
;
PPAR alpha
;
genetics
;
metabolism
;
Plasticizers
;
toxicity
;
Rats
2.Experimental Study on Migration Parameters of DEHP in PVC Infusion.
Jun WANG ; Yan WU ; Shiyong BAO ; Hongqiang JIANG ; Guoli SHEN ; Ningqing CHEN
Chinese Journal of Medical Instrumentation 2019;43(2):132-135
The work explored the DEHP migration parameters in PVC infusion in clinic,based on the previous research on the test model of DEHP migrated from PVC infusion,to assess the safety of PVC infusion.The leaching solution samples in different conditions were evaluated by analysis of the DEHP in leaching solution using GC-MS under simulated clinical transfusion way.The release behavior of DEHP was significantly affected by the storage time,storage temperature,surrounding temperature,dripping speed,sterilization process,volume of the leaching solution,and the property of the leaching solution.
Diethylhexyl Phthalate
;
pharmacokinetics
;
Gas Chromatography-Mass Spectrometry
;
Plasticizers
;
pharmacokinetics
;
Polyvinyl Chloride
;
pharmacokinetics
;
Temperature
3.Application and Safety Evaluation of DEHP in PVC Medical Devices.
Yue WANG ; Xin XIE ; Hongqiang JIANG ; Jun WANG
Chinese Journal of Medical Instrumentation 2018;42(4):293-295
DEHP is largely used in soft PVC products as the plasticizer, which is also widely applied in medical devices. Due to its potential and widespread toxicity and medical devices' specific use, the safety of DEHP's application in medical devices has received extensive attention. In this paper, a comprehensive review of the application and potential toxicity of DEHP in PVC medical devices is made on the basis of the research results all over the world. Besides, the safety evaluation in medical devices is discussed and some possible coping strategies are explored.
Diethylhexyl Phthalate
;
adverse effects
;
Equipment Safety
;
Equipment and Supplies
;
adverse effects
;
Plasticizers
;
adverse effects
;
Polyvinyl Chloride
4.Research on Experimental Model of Security Assessment of DEHP Migration from PVC-Tubes Medical Devices.
Yue WANG ; Shiyong BAO ; Guoli SHEN ; Jun WANG ; Hongqiang JIANG
Chinese Journal of Medical Instrumentation 2018;42(3):222-224
As we all know, DEHP is seriously harmful to human health and consequently has been acquired critical attention. DEHP is able to migrate from PVC medical devices for the non-chemically bound to PVC, thus contact with user and patient. The DEHP migration is influenced by various parameters. In order to assess the security of PVC-tubes medical devices scientifically of DEHP migration, we develop an experimental model by analyzing the parameters comprehensively and systematically, taking into account the clinical practices. For example, assessing the security of DEHP migration from infusion sets by utilizing this model.
Diethylhexyl Phthalate
;
adverse effects
;
Equipment and Supplies
;
Humans
;
Models, Theoretical
;
Plasticizers
;
adverse effects
;
Polyvinyl Chloride
5.Environmental Pollution and Diabetes.
Journal of Korean Diabetes 2018;19(2):76-81
Endocrine disrupting chemicals (EDCs) are exogenous chemicals contained in industrial substances and plasticizers commonly utilized worldwide. Human exposure to such chemicals, particularly at low-doses, is omnipresent, persistent, and occurs in complex mixtures. EDCs include bisphenol A, phthalates, pesticides, and persistent organic pollutants such as polychlorinated biphenyls. Burgeoning epidemiological, animal, and cellular data link environmental EDCs to metabolic dysfunction. In the last three decades, the number of diabetic patients has drastically increased worldwide, with current statistics suggesting that the number will double in the next two decades. There is epidemiological and experimental evidence linking background exposure to a selection of environmental EDCs with diabetes and impaired glucose metabolism. EDC may be related to increased risk of diabetes.
Animals
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Complex Mixtures
;
Endocrine Disruptors
;
Environmental Pollution*
;
Glucose
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Humans
;
Metabolism
;
Pesticides
;
Plasticizers
;
Plastics
;
Polychlorinated Biphenyls
6.Hypospadias induced by maternal exposure to di-n-butyl phthalate and its mechanisms in male rat offspring
En-Hui LI ; Hai-Bin WEI ; Bang-Gao LHUANGI ; En-Hui LI ; Qi ZHANG ; Zhi-Hui XU ; Da-Hong ZHANG
National Journal of Andrology 2017;23(12):1063-1068
Objective:
To induce hypospadias in male rat offspring by maternal exposure to di-n-butyl phthalate (DBP) during late pregnancy and further investigate its mechanisms.
METHODS:
We randomly divided 20 pregnant rats into a DBP exposure and a control group, the former treated intragastrically with DBP while the latter with soybean oil at 750 mg per kilogram of the body weight per day from gestation days (GD) 14 to 18. On postnatal day (PND) 1, we recorded the incidence rate of hypospadias and observed the histopathological changes in the genital tubercle of the hypospadiac rats. We also measured the level of serum testosterone (T) by radioimmunoassay and determined the mRNA and protein expressions of the androgen receptor (AR), sonic hedgehog (Shh), bone morphogenetic protein 4 (Bmp4) and fibroblast growth factor 8 (Fgf8) in the genital tubercle by real-time PCR and Western blot.
RESULTS:
No hypospadiac male rats were found in the control group. The incidence rate of hypospadias in male offspring was 43.6% in the DBP-treatment group. Histological analysis confirmed hypospadiac malformation. The serum testosterone concentration was decreased in the hypospadiac male rats as compared with the controls ([0.49 ± 0.05] vs [1.12 ± 0.05] ng/ml, P <0.05). The mRNA expressions of AR, Shh, Bmp4 and Fgf8 in the genital tubercle were significantly lower in the hypospadiac male rats than in the controls (AR: 0.50 ± 0.05 vs 1.00 ± 0.12, P <0.05; Shh: 0.65 ± 0.07 vs 1.00 ± 0.15, P <0.05; Bmp4: 0.42 ± 0.05 vs 1.00 ± 0.13, P <0.05; Fgf8: 0.46 ± 0.04 vs 1.00 ± 0.12, P <0.05), and so were their protein expressions (AR: 0.34 ± 0.05 vs 1.00 ± 0.09, P <0.05; Shh: 0.51 ± 0.07 vs 1.00 ± 0.12, P <0.05; Bmp4: 0.43 ± 0.05 vs 1.00 ± 0.11, P <0.05; Fgf8: 0.57 ± 0.04 vs 1.00 ± 0.13, P <0.05).
CONCLUSIONS
Maternal exposure to DBP during late pregnancy can induce hypospadias in the male rat offspring. DBP affects the development of the genital tubercle by reducing the serum T concentration and expressions of AR, Shh, Bmp4 and Fgf8 in the genital tubercle, which might underlie the mechanism of DBP inducing hypospadias.
Animals
;
Body Weight
;
Bone Morphogenetic Protein 4
;
blood
;
Dibutyl Phthalate
;
toxicity
;
Female
;
Fibroblast Growth Factor 8
;
blood
;
Hedgehog Proteins
;
blood
;
Hypospadias
;
blood
;
chemically induced
;
pathology
;
Male
;
Maternal Exposure
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Plasticizers
;
toxicity
;
Pregnancy
;
RNA, Messenger
;
blood
;
Random Allocation
;
Rats
;
Rats, Sprague-Dawley
;
Receptors, Androgen
;
blood
;
Soybean Oil
;
Testosterone
;
blood
7.Risk assessment of di(2-ethylhexyl) phthalate in the workplace.
Environmental Health and Toxicology 2016;31(1):e2016011-
OBJECTIVES: A hazard assessment of di(2-ethylhexyl) phthalate (DEHP), a commonly used workplace chemical, was conducted in order to protect the occupational health of workers. A literature review, consisting of both domestic and international references, examined the chemical management system, working environment, level of exposure, and possible associated risks. This information may be utilized in the future to determine appropriate exposure levels in working environments. METHODS: Hazard assessment was performed using chemical hazard information obtained from international agencies, such as Organization for Economic Cooperation and Development-generated Screening Information Data Set and International Program on Chemical Safety. Information was obtained from surveys conducted by the Minister of Employment and Labor (“Survey on the work environment”) and by the Ministry of Environment (“Survey on the circulation amount of chemicals”). Risk was determined according to exposure in workplaces and chemical hazard. RESULTS: In 229 workplaces over the country, 831 tons of DEHP have been used as plasticizers, insecticides, and ink solvent. Calculated 50% lethal dose values ranged from 14.2 to 50 g/kg, as determined via acute toxicity testing in rodents. Chronic carcinogenicity tests revealed cases of lung and liver degeneration, shrinkage of the testes, and liver cancer. The no-observed-adverse-effect level and the lowest-observed-adverse-effect level were determined to be 28.9 g/kg and 146.6 g/kg, respectively. The working environment assessment revealed the maximum exposure level to be 0.990 mg/m³, as compared to the threshold exposure level of 5 mg/m³. The relative risk of chronic toxicity and reproductive toxicity were 0.264 and 0.330, respectively, while the risk of carcinogenicity was 1.3, which is higher than the accepted safety value of one. CONCLUSIONS: DEHP was identified as a carcinogen, and may be dangerous even at concentrations lower than the occupational exposure limit. Therefore, we suggest management of working environments, with exposure levels below 5 mg/m³ and all workers utilizing local exhaust ventilation and respiratory protection when handling DEHP.
Carcinogenicity Tests
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Chemical Safety
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Clergy
;
Dataset
;
Diethylhexyl Phthalate
;
Employment
;
Humans
;
Ink
;
Insecticides
;
International Agencies
;
Liver
;
Liver Neoplasms
;
Lung
;
Mass Screening
;
No-Observed-Adverse-Effect Level
;
Occupational Exposure
;
Occupational Health
;
Plasticizers
;
Plastics
;
Risk Assessment*
;
Rodentia
;
Testis
;
Toxicity Tests, Acute
;
Ventilation
8.Dietary Exposure to Benzyl Butyl Phthalate in China.
Lei ZHANG ; Ding Guo JIANG ; Hai Xia SUI ; Ping Gu WU ; Ai Dong LIU ; Da Jin YANG ; Zhao Ping LIU ; Yan SONG ; Ning LI
Biomedical and Environmental Sciences 2016;29(5):365-373
OBJECTIVEBenzyl butyl phthalate (BBP) is a plasticizer used in food contact materials. Dietary exposure to BBP might lead to reproduction and developmental damages to human. The present paper was aimed to assess the health risk of BBP dietary exposure in Chinese population.
METHODSThe BBP contents were detected in 7409 food samples from 25 food categories by gas chromatography-mass spectrometry operated in selected ion monitoring (SIM) mode. The dietary exposures of BBP in different age and sex groups were estimated by combining the content data with food consumption data derived from 2002 China National Nutrient and Health Survey, and evaluated according to the tolerable daily intake (TDI) of BBP established by European Food safety Agency.
RESULTSIt was found that BBP was undetectable in most samples and the highest level was 1.69 mg/kg detected in a vegetable oil sample. The average dietary exposure of BBP in people aged ⋝2 years was 1.03 μg/kg bw per day and the highest average exposure was found in 2-6 years old children (1.98 μg/kg bw per day). The BBP exposure in 7-12 months old children excessed 10% of tolerable daily intake (TDI) in worst scenario. .
CONCLUSIONThe health risk of BBP dietary exposure in Chinese population is low and, considering BBP alone, there is no safety concern.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; China ; Diet ; Environmental Exposure ; Environmental Pollutants ; analysis ; Female ; Food Contamination ; analysis ; Food Packaging ; Gas Chromatography-Mass Spectrometry ; Humans ; Male ; Middle Aged ; Phthalic Acids ; analysis ; Plasticizers ; analysis ; Young Adult
9.Determination of Plasticizer DEHP Released from Medical Injection Equipment.
Jian ZHENG ; Minzhu WANG ; Wang ANYAN ; Pinghua XU ; Yin HAN ; Yan WEN ; Li ZHANG
Chinese Journal of Medical Instrumentation 2015;39(6):451-453
To established an effective GC-MS /MS method for the contents determination of the residual DEHP in injection equipment, and investigate the effect of the pretreatment on the measurement. To simulate the clinical conditions of use, under the condition of 37 degrees C balance extraction, extract liquor by chloroform extraction, then the extract followed by analysis of GC-MS /MS. The method was simple, rapid, sensitive and accurate. The limits of quantitation (LOQ, S/N = 5) of cyclohexanone was 0.075 μg/mL, The spiked average recoveries ranged from 92% to 98%. The relative standard deviations (RSDs) of the method ranged from 1.01% to 1.61%, The method was simple, fast, sensitive and accurate, and may serve as a mass control method for residual DEHP in injection equipment.
Cyclohexanones
;
chemistry
;
Diethylhexyl Phthalate
;
chemistry
;
Equipment Contamination
;
Gas Chromatography-Mass Spectrometry
;
Injections
;
instrumentation
;
Limit of Detection
;
Plasticizers
;
chemistry
10.Phthalate exposure and childhood obesity.
Annals of Pediatric Endocrinology & Metabolism 2014;19(2):69-75
Phthalates are commonly used as plasticizers and vehicles for cosmetic ingredients. Phthalate metabolites have documented biochemical activity including activating peroxisome proliferator-activated receptor and antiandrogenic effects, which may contribute to the development of obesity. In vitro and in vivo studies suggest that phthalates have significant effects on the development of obesity, especially after prenatal exposure at low doses. Although few studies have examined the effects of phthalate on obesity development in humans, some work has shown that phthalates affect humans and animals similarly. In this paper, we review the possible mechanisms of phthalate-induced obesity, and discuss evidence supporting the role of phthalates in the development of obesity in humans.
Animals
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Child
;
Diethylhexyl Phthalate
;
Endocrine Disruptors
;
Humans
;
Obesity
;
Pediatric Obesity*
;
Peroxisomes
;
Plasticizers
;
Plastics

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