Effects of Diethyl Phthalate and Other Plasticizers on Laurate Hydroxylation in Rat Liver Microsomes

Diethyl phthalate (DEP) is used in pharmaceutical coatings, cosmetics, and plastic films to wrap foods. There is a health concern associated with the exposure to certain phthalate esters because they belong to a class of compounds referred to as peroxisome proliferators which have been shown to increase the incidence of liver tumors when administered to rats. In this study, we have compared DEP to four other commonly used plasticizers, 2-diethylhexyl phthalate (DEHP), dibutyl phthalate (DBP), 2-diethylhexyl adipate (DEHA), and acetyltributyl citrate (ATBC), for their ability to induce the cytochrome P450-mediated fatty acid -hydroxylation system, which is one of the initial cellular responses when animals are treated with peroxisome proliferators. The administration of DEHP, DBP, and DEHA to rats increased the specific activity of laurate 12-hydroxylase from 2.8 ± 1.1 in control rats to 30.3 ± 11.6, 14.5 ± 4.1, and 9.7 ± 1.9 nmol 12-hydroxylaurate formed/min/nmol P450, respectively. In contrast, laurate 12-hydroxylase activity in DEP-and ATBC-treated rats were 4.4 ± 1.2 and 4.4 ± 1.0 nmol 12-hydroxylaurate formed/min/nmol P450, respectively. In addition, whereas DEHP increased peroxisomal palmitoyl-CoA oxidation 6-fold, DEP increased this activity only 1.3-fold. Two protein bands, at 51 and 52 kDa, were found to increase 6- to 12-fold in microsomes of DEHP-, DBP-, and DEHA-treated rats, but these bands were increased only 2-fold in DEP- or ATBC-treated rats.     

利用近红外光谱技术快速检测邻苯二甲酸酯类物质

目的:以红茶为研究载体,应用近红外光谱技术建立食品、药品中塑化剂的快速检测方法.方法:测定了加入4种邻苯二甲酸酯类的红茶饮料的近红外光谱数据,经过光谱预处理,以偏最小二乘法(PLS)建立回归模型,用于饮料中塑化剂总量以及单一塑化剂含量的定量分析.结果:塑化剂总量,邻苯二甲酸甲酯,邻苯二甲酸乙酯,邻苯二甲酸丁酯,邻苯二甲酸辛酯定量模型的决定系数(R2)分别为0.9923,0.9895,0.9927,0.9842,0.9879.预测模型的外部验证相关系数(r)依次为0.9877,0.9881,0.9891,0.9771,0.9762.预测集标准偏差(RMSEP)依次为0.1640,0.1470,0.0276,0.0258,0.0702.结论:近红外光谱技术对塑化剂的定量分析具有较高的准确度,可将其作为食品、药品中塑化剂含量的快速检测方法.     

Allergic contact dermatitis from di-isodecyl phthatate in a polyvinyl chloride identity band

An animal model for the evaluation of skin protective creams against chemical irritants is described. The irritants were applied daily for 2 weeks to shaved back skin of young guinea pigs: sodium tauryl sulphate (5% aq.: 30 min), sodium hydroxide (0,5% aq.; 2 min). and toluene (20′i. eth.; 2 mint. “The harrier cream was applied 2 h prior to and immediately after exposure to the irritant. Control animals were treated with the irritant only. The irritant reaction was scored on a 4–point scale for erythema and quantified with regard to transepidennal water loss (TEWL) by evaporime-try and skin blood flow volume (BFV) by laser Doppler velocimetry. A total of 90 guinea pigs, consisting of” individual panels of 5 to 10 animals, was tested. While one barrier cream (Slokoderm) significantly suppressed the irritation due 10 sodium lauryl sulphate and toluene, the other (Contra-Alkalh failed to do so and even aggravated the response, which was particularly evident with sodium hydroxide. This model may be useful in developing more effective barrier creams.     

A case of contact urticaria syndrome due to di(2-ethylhexyl) phthalate (DOP) in work clothes

We previously reported a case of contact urticaria syndrome (CUS) due to di(2-ethylhexyl) phthalate (DOP) in a polyvinyl chloride (PVC) grip on cotton gloves. The patient reported in this previous paper was careful not to have any contact with PVC products in his daily life or in his working environment. He discontinued the use of protective gloves with a PVC grip that was the cause of CUS. When working, he used cotton gloves without a PVC grip. We prescribed antihistamines which slightly improved his condition. However, when he wore work clothes while on duty, CUS relapsed. This condition was severe and made him feel anxious. When we advised him to wear a cotton shirt under his work clothes, the contact urticaria did not develop. We suspected that some component of the work clothes was the cause of his symptoms. A prick test with the extract solution of his work clothes showed a wheal and flare at the 15 min reading. The common component of the grip and the work clothes was found by analysis to be DOP.     

Eudragit~ NE 30 D和Eudragit~ L 30 D-55混合游离膜吸湿性研究

目的研究以Eudragit~NE 30 D和Eudragit~ L 30 D-55水分散体混合制备缓释衣膜。方法采用平面铸膜法制备混合游离膜,采用杯法测定其透湿系数。结果混合游离膜的透湿量和表观膜厚无关,增塑剂的含量及种类对透湿量影响显著。结论混合游离膜有良好的吸湿性。     

控释包衣膜中增塑剂含量的HPLC测定

建立了高效液相色谱法测定控释包衣膜中增塑剂含量,采用Hypersil C18柱,甲醇为流动相,检测波长为217和260nm,分别测定柠檬酸三乙酯（TEC）,柠檬酸三丁酯（TBC）,三醋酸甘油酯（TR）,邻苯二甲酸二甲酯（DMP）,邻苯二甲酸二乙酯（DEP）,邻苯二甲酸二丁酯（DBP）的含量,其中DMP,DEP和DBP在5－87ug/ml,TEC,TBC,TR在130－2300ug/ml浓度范围内与峰高呈良好的线性关系（r=0.9999),方法的日内及日间精密度,回收率均符合药物分析要求。     

渗透型丙烯酸树脂包衣控释膜中增塑剂的优选

目的　筛选适合渗透型丙烯酸树脂 Eudragit RS100 膜控释包衣的增塑剂。方法　通过测定膜玻璃化转变温度(Tg)、膜水化前后两种状态的力学性能,研究不同增塑剂的增塑效率;用溶出度和水平扩散池法考察增塑剂从介质中溶出;用加速试验考察贮存时增塑剂的损失。结果　Tg显示EudragitRS10 0具较强增塑剂相容性,水溶性增塑剂三醋酸甘油酯(TR)和水不溶性增塑剂邻苯二甲酸二丁酯(DBP)等均有较高增塑效率;膜水化前后力学性能变化显著,水溶性增塑剂遇介质从膜中快速溶出使湿膜脆碎,而水不溶性增塑剂则相对稳定;于(40±1)℃、相对湿度(RH)75%下贮存40d ,膜TR损失达6.46% ,而DBP仅损失0.29%。结论　DBP等水不溶性增塑剂是较理想的 Eudragit RS100 膜控释包衣膜增塑剂品种     

一次性使用输液器中邻苯二甲酸酯增塑剂的迁移及影响因素分析

目的 研究一次性使用输液器中邻苯二甲酸酯在注射液中的迁移规律。方法 将21种注射液根据其性质分成6组,按照临床常用浓度,以每分钟40滴的速度模拟临床输液,收集2 h流出液。按DLLME-GC-MS方法测定流出液中邻苯二甲酸酯的含量。同时考察辅料、接触时间对一次性使用输液器中邻苯二甲酸迁移的影响。结果 邻苯二甲酸酯能向其中12种流经一次性使用输液器的注射液迁移。其中在盐酸胺碘酮注射液中,DEHP和DBP的迁移量最大,DBP的迁移量为2.67 μg,DEHP的迁移量为104.8 μg。聚山梨酯-80、乙醇、丙二醇和苯甲醇等辅料均能促进输液器中的邻苯二甲酸酯的迁移,迁移量随辅料浓度的提高而增大。同时延长接触时间,输液器中邻苯二甲酸的迁移量也随之升高。结论 一次性使用输液器中的邻苯二甲酸酯能向与之接触的注射液迁移。迁移量与注射液中的聚山梨酯-80、乙醇、丙二醇和苯甲醇的含量有关,也和接触时间有关。     

Mortality and cancer morbidity in workers exposed to low levels of vinyl chloride monomer at a polyvinyl chloride processing plant

To study whether exposure to low levels of vinyl chloride monomer (VCM) causes increased risk for cancer morbidity and death from ischemic heart disease, a cohort study was performed among 2,031 male workers at a polyvinyl chloride (PVC) processing plant who had been employed for at least 3 months during the period 1945-1980. An almost significantly increased total mortality (SMR = 116, 95% CI 99-136) was found. Deaths caused by violence or intoxication were significantly increased (SMR = 153, 95% CI 109-213), but not deaths from ischemic heart disease (SMR = 100, 95% CI 73-135). A significant increase in total cancer morbidity was observed (SMR = 128, 95% CI 101-161). Respiratory cancers were significantly increased (SMR = 213, 95% CI 127-346). Furthermore, six brain tumors (vs. 2.6 expected) were observed. This increase, however, was not significant (SMR = 229, 95% CI 84-498). No liver hemangiosarcoma was observed. Applying a latency period of greater than or equal to 10 years from start of employment did not change the risk patterns. There were no significant exposure-response associations between exposure estimates for VCM, asbestos, and plasticizers and cancer morbidity.