单细胞凝胶电泳检测酞酸酯类对DNA的损伤

目的应用单细胞凝胶电泳(SCGE)技术对增塑剂(DEHP)邻苯二甲酸二乙基己酯致小鼠胚胎成纤维细胞(3T6细胞)DNA损伤、损伤程度以及有无剂量-效应关系进行检测.方法将溶剂二甲基亚砜处理的3T6细胞作为阴性对照组,用H2O2染毒的3T6细胞作为阳性对照组(80μmol/L H2O2染毒),将不同浓度DEHP处理的3T6细胞设为4个剂量组(62.5,125,250,500μg/ml)进行SCGE检验.结果各染毒组细胞DNA损伤与阴性对照组比较,均有显著性差异(P＜0.05);且随DEHP染毒浓度增加,3T6细胞DNA损伤程度加重,有剂量-效应关系.结论 DEHP体外染毒对3T6细胞能造成损伤,且随剂量的增加有加重的趋势.     

Di(2‐ethylhexyl) phthalate (DEHP) influences follicular development in mice between the weaning period and maturity by interfering with ovarian development factors and microRNAs

Although studies have shown that di(2‐ethylhexyl) phthalate (DEHP) can disrupt ovarian function, few reports have focused on follicular development in mice between the weaning period and maturity, especially with respect to microRNA (miRNA) expression. In this study, 21‐day‐old ICR mice were administered DEHP at doses of 0, 100, 400, and 1600 mg/(kg d) for 6 weeks by gavage. After DEHP administration, a significant decrease in the expression of follicle development‐related factors (including c‐kit, kitl, gdf9, and atm) was observed by quantitative real‐time PCR (RT‐PCR), but no significant difference in the proteins encoded by these genes was observed by Western blot. Bisulfite sequencing suggested that the total methylation percentages of promoter regions of these genes were not notably altered after DEHP exposure. However, RT‐PCR revealed a significantly increased expression of ovarian miRNAs (let‐7b, miR‐17‐5p miR‐181a, and miR‐151), which inhibit follicular granulosa cell proliferation. Overall, this study showed that DEHP administration from weaning to maturity could suppress the mRNA expression of follicular development factors, and this effect was not achieved through changes in the methylation of DNA in CpG islands of development factors. In addition, DEHP was shown to induce miRNAs to inhibit the proliferation of follicular granulosa cells and the anti‐apoptosis function of KITL and GDF9 while increasing bax/bcl₂ expression to further promote the apoptosis of granulosa cells.     

Skin permeation and metabolism of di(2-ethylhexyl) phthalate (DEHP)

Phthalates are suspected to be endocrine disruptors. Di(2-ethylhexyl) phthalate (DEHP) is assumed to have low dermal absorption; however, previous in vitro skin permeation studies have shown large permeation differences. Our aims were to determine DEHP permeation parameters and assess extent of skin DEHP metabolism among workers highly exposed to these lipophilic, low volatile substances.     

Cryptorchidism and endocrine disrupting chemicals

Prospective clinical studies have suggested that the rate of congenital cryptorchidism has increased since the 1950s. It has been hypothesized that this may be related to environmental factors. Testicular descent occurs in two phases controlled by Leydig cell-derived hormones insulin-like peptide 3 (INSL3) and testosterone. Disorders in fetal androgen production/action or suppression of Insl3 are mechanisms causing cryptorchidism in rodents. In humans, prenatal exposure to potent estrogen diethylstilbestrol (DES) has been associated with increased risk of cryptorchidism. In addition, epidemiological studies have suggested that exposure to pesticides may also be associated with cryptorchidism. Some case-control studies analyzing environmental chemical levels in maternal breast milk samples have reported associations between cryptorchidism and chemical levels. Furthermore, it has been suggested that exposure levels of some chemicals may be associated with infant reproductive hormone levels.     

Thyroid effects of endocrine disrupting chemicals

In recent years, many studies of thyroid-disrupting effects of environmental chemicals have been published. Of special concern is the exposure of pregnant women and infants, as thyroid disruption of the developing organism may have deleterious effects on neurological outcome. Chemicals may exert thyroid effects through a variety of mechanisms of action, and some animal experiments and in vitro studies have focused on elucidating the mode of action of specific chemical compounds. Long-term human studies on effects of environmental chemicals on thyroid related outcomes such as growth and development are still lacking. The human exposure scenario with life long exposure to a vast mixture of chemicals in low doses and the large physiological variation in thyroid hormone levels between individuals render human studies very difficult. However, there is now reasonably firm evidence that PCBs have thyroid-disrupting effects, and there is emerging evidence that also phthalates, bisphenol A, brominated flame retardants and perfluorinated chemicals may have thyroid disrupting properties.     

PVC材质一次性输注泵在常用局麻药应用中的安全性研究

目的考察一次性使用输注泵与常用局麻药的相容性,评定其在临床常用局麻药物使用中的安全性。方法3种常用局麻药分别与2种液体（生理盐水及乳酸林格氏液）按临床使用浓度配伍,在不同时间点分别采用LC-MS／MS法、光阻法、高效液相色谱法测定邻苯二甲酸二-（2-乙基己基）酯（DEHP）含量、不溶性微粒和药物浓度。结果DEHP含量低于LC-MS／MS测定方法定量下限（0．072gg·mL^-1）,更低于考核标准静脉晶体溶液输注成年人（70kg）DEHP剂量上界估算值（0．005mg·kg^-1·d^-1）;48h内各实验药物在一次性使用输注泵中药物含量相对0h均〉96．0％,受试输注泵与各种药物在48h内未见明显吸附;输注泵中溶液稳定,0h每1mL粒子直径≥10μm粒子数（n=30）（35．13±14．4）粒;每1mL粒子直径≥25μm粒子数（n=30）（0．61±0．49）粒,符合中国药典2010版标准。结论研究表明本一次性使用输注泵应用于3种常用局麻药物较为稳定,其DEHP溶出、不溶性微粒及药物吸附性等方面符合安全使用要求。     

一次性无菌注射器的浸出有机物研究

目的:研究一次性无菌注射器(简称一次性注射器)与有机助溶剂接触后的浸出有机物,确定其结构并测定含量。方法:采用含橡胶活塞的三件式一次性注射器及不含橡胶活塞的二件式一次性注射器与注射剂中常用的乙醇、丙二醇、聚乙二醇400及甘油等有机助溶剂接触,采用高效液相色谱-二极管阵列检测器、质谱确定浸出有机物的结构;模拟已上市注射剂处方,以高效液相色谱法定量测定一次性注射器分别与5%²0%乙醇溶液、20%20%乙醇溶液、20%⁶0%丙二醇溶液及20%60%丙二醇溶液及20%⁶0%聚乙二醇400溶液接触后浸出有机物的含量。结果:三件式一次性注射器与甘油接触后无明显浸出有机物;与乙醇、丙二醇及聚乙二醇400接触后有有机物浸出,其中乙醇中浸出量最高;二件式一次性注射器与上述有机助溶剂接触均无浸出物出现。浸出有机物来源于注射器中的橡胶活塞,为增塑剂邻苯二甲酸二异辛酯(DEHP)。一次性注射器与不同浓度的有机助溶剂接触5 min以内,浸出的DEHP含量均低于1.5μg/ml,远低于人体可耐受的日摄入量。结论:采用一次性注射器注射含有机助溶剂的注射剂,短时间内使用安全性风险较低。     

Phthalate plasticizer di(2‐ethyl‐hexyl) phthalate induces cyclooxygenase‐2 expression in gastric adenocarcinoma cells

The phthalate plasticizer, di(2‐ethyl‐hexyl) phthalate (DEHP), and its derived metabolites are common anthropogenic environmental toxins, which are known to act as endocrine disruptors. Numerous studies have associated DEHP with disruption of sex hormones, abnormal development of reproductive organs, allergies, and inflammation. Its role in promoting inflammation has been reported by both human epidemiological and animal studies. In stomach tissue, chronic inflammation is known to accompany mucosal damage, and pave the way to gastritis, stomach ulcers, and ultimately gastric cancer. Eastern Asian populations possess the highest gastric cancer incidences in the world. Coincidentally, East Asia is one of the world's major sites for plastics manufacture and export. Thus, possible correlations between DEHP, a common plasticizer, and gastric cancer are of great interest. Our study revealed several critical findings. First, even at very low dosage, mimicking the residual plasticizer exposure, detrimental effects of DEHP on gastric cells can be detected. Second, gastric cells treated with DEHP increased cyclooxygenase‐2 (COX‐2) in a time‐dependent manner. Third, promoter deletion studies revealed a critical role of nuclear factor‐kappa B (NF‐κB) for COX‐2 gene responses. Finally, our results indicated that a low concentration of DEHP is able to trigger COX‐2 activation via the extracellular signal–regulated kinase (ERK1/2) and NF‐κB signaling pathway. Taken together, we demonstrate that very low doses of DEHP enhance the expression of the prototypical inflammatory gene, COX‐2, in gastric cancer cells via ERK1/2 and NF‐κB activation. This study provides important insights into the inflammatory process and damages associated with phthalate plasticizers exposure.     

Plasticizer Contamination of Firefighter Personal Protective Clothing – A Potential Factor in Increased Health Risks in Firefighters

Chemical exposures may be responsible for firefighters’ elevated incidences of cancer and cardiovascular disease. This study characterized semivolatile chemical contamination on firefighter personal protective clothing to assess exposure of firefighters to these chemicals. Samples from used firefighter protective clothing, including gloves, hood, and one coat wristlet, were extracted with methylene chloride and analyzed by EPA method 8270 for semivolatile contaminants, including 20 polycyclic aromatic hydrocarbons (PAHs) and 6 phthalate diesters. Twenty-two of the chemicals of interest were found on at least one clothing swatch. Only di-(2-ethylhexyl) phthalate (DEHP), a plasticizer, added to polyvinyl chloride (PVC) to increase flexibility, was found on every swatch. DEHP concentrations were the highest of any chemical measured, and were 52 to 875 times higher than any PAH concentration measured. DEHP was also detected on most items of unused firefighter personal protective clothing, although at much lower levels. These findings suggest that firefighters are exposed to high levels of DEHP, a probable human carcinogen, and at levels much higher than PAHs, the semivolatile toxic combustion products most extensively studied historically. Firefighter exposure to DEHP and other phthalate diesters therefore merits further study.