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Journal of Toxicology-cutaneous and Ocular Toxicology最新文献

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Skin contamination and absorption of chemicals from water and soil 皮肤污染和从水和土壤中吸收化学物质
Pub Date : 2001-01-01 DOI: 10.1081/CUS-120001863
R. Wester, H. Maibach
Contamination of soil and water (ground and surface water) and the transfer of hazardous chemicals is a major concern. When the large surface area of skin is exposed to contaminated soil and water (work, play, swim, daily bath), skin absorption may be significant. Brown et al. (1) suggested that skin absorption of contaminants in water has been underestimated and that ingestion may not constitute the sole, or even the primary route of exposure. Soil has become an environmental depository for potentially hazardous chemicals. Exposure through work in pesticide-sprayed areas on chemical dump sites seems obvious. However, there may be hidden dangers in weekend gardening or in the child’s play area where the soil has become laden with lead or other hazardous chemicals.
土壤和水(地下水和地表水)的污染以及危险化学品的转移是一个主要问题。当皮肤大面积暴露于受污染的土壤和水(工作、玩耍、游泳、日常洗澡)时,皮肤吸收可能显著。Brown等人(1)认为,皮肤对水中污染物的吸收被低估了,摄入可能不是唯一的,甚至不是主要的暴露途径。土壤已成为潜在危险化学品的环境贮存地。在化学品倾倒场喷洒农药的地区,通过工作接触农药似乎是显而易见的。然而,在周末园艺或儿童游乐区可能存在潜在的危险,那里的土壤已经充满了铅或其他有害化学物质。
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引用次数: 11
EFFECT OF JP-8 JET FUEL EXPOSURE ON THE ULTRASTRUCTURE OF SKIN 喷气燃料暴露对皮肤超微结构的影响
Pub Date : 2001-01-01 DOI: 10.1081/CUS-100000336
Somnath Singh, Jagdish Singh
Fuel system maintenance usually requires direct, prolonged exposure to fuel. Thus, both military and commercial aircraft workers are at risk of dermal exposure and toxicity from JP-8 jet fuel. At present, there are no standards for U.S. Air Force personnel regarding dermal exposure to jet fuel. Hence, there are needs for data and approaches to understand the human hazard from dermal exposure to JP-8. In this study, we investigated the alteration in porcine skin at ultrastructural level, after a 24-h exposure to JP-8, with the help of transmission electron microscopy (TEM). Many ultrastructural modifications were noticed in the photomicrographs. Large-scale expansion in intercellular lipid domains of stratum corneum and disruption in its structural integrity; alteration in configuration of basal cells; rupture of hemidesmosomes and desmosomes; and diminished dendritic processes in Langerhans cells were observed. It is concluded that JP-8 exposure can cause alteration in skin anatomy, which may lead to dermal toxicity. Further studies are required to determine comparative damages incurred by individual components of JP-8.
燃油系统维护通常需要长期直接接触燃油。因此,军用和商用飞机工作人员都有皮肤暴露和JP-8喷气燃料毒性的风险。目前,美国空军人员的皮肤接触喷气燃料方面还没有标准。因此,需要数据和方法来了解皮肤暴露于JP-8对人体的危害。在本研究中,我们利用透射电子显微镜(TEM)研究了暴露于JP-8 24小时后猪皮肤超微结构水平的变化。显微照片上观察到许多超微结构的改变。角质层细胞间脂质结构域的大规模扩张及其结构完整性的破坏;基底细胞形态改变;半端粒和桥粒破裂;朗格汉斯细胞树突突减少。由此可见,JP-8暴露可引起皮肤解剖结构的改变,从而导致皮肤毒性。需要进一步的研究来确定JP-8的各个组成部分所造成的相对损害。
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引用次数: 3
Determination of percutaneous absorption by in vitro techniques 体外透皮吸收测定技术
Pub Date : 2001-01-01 DOI: 10.1081/CUS-120001867
R. Bronaugh, H. Hood, M. Kraeling, J. Yourick
In vitro percutaneous absorption methods have become widely used for measuring the absorption of compounds that come in contact with skin. Safety evaluations of toxic chemicals frequently rely on in vitro studies for human permeation data. Animal data must be used cautiously for estimating human absorption due to differences in barrier properties of animal and human skin (1). In vitro absorption studies can also be used to measure skin metabolism if viable skin is obtained for the study and if the viability is maintained in the diffusion cells (2). The in vitro system allows for the isolation of skin so that metabolism of the organ can be distinguished from systemic metabolism. Important considerations is conducting in vitro absorption studies are discussed in the following sections.
体外经皮吸收法已被广泛用于测量与皮肤接触的化合物的吸收。有毒化学品的安全性评估往往依赖于人体渗透数据的体外研究。由于动物和人类皮肤屏障特性的差异,在估计人体吸收时必须谨慎使用动物数据(1)。如果获得可存活的皮肤并在扩散细胞中保持活力,则体外吸收研究也可用于测量皮肤代谢(2)。体外系统允许隔离皮肤,以便将器官的代谢与全身代谢区分开来。进行体外吸收研究的重要考虑因素将在以下章节中讨论。
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引用次数: 14
An innovative method to determine percutaneous absorption: Real-time breath analysis and physiologically based pharmacokinetic modeling 一种测定经皮吸收的创新方法:实时呼吸分析和基于生理的药代动力学建模
Pub Date : 2001-01-01 DOI: 10.1081/CUS-120001873
K. Thrall, T. Poet, R. Corley
From the 1950s through the 1970s, the rate of uptake of a chemical through the skin was generally estimated from studies of humans using radiolabeled compounds (1). More recently, estimates of dermal absorption have been made using animal (in vivo or in vitro) or human (in vitro) skin. In vivo percutaneous absorption in animals is usually determined by measuring radioactivity in blood and excreta following a topical application of the labeled compound. This indirect method of determining percutaneous absorption provides an estimate of the total absorbed dose, but often fails to reveal information on absorption kinetics. To date, the only way to determine the absolute bioavailability of a topically applied compound is to compare the concentrations in blood or urine following topical and intravenous administration (2). Since blood levels may be very low in these situations, this practice is often restricted by the sensitivity limits of the assay or analysis. As an alternative to conducting radiotracer studies, a new, real-time breath analysis system coupled with physiologically based pharmacokinetic (PBPK) modeling has been developed to determine percutaneous absorption in rats and humans in vivo (3). With this system, a topical dose of a compound can be applied to a specified skin surface area, and the breath analysis system can be used to monitor the concentration of that compound and/or its metabolites in the exhaled breath. A PBPK model, modified to describe the dermal exposure, can than be used to determine the skin permeability constant under various exposure situations.
从20世纪50年代到70年代,化学物质通过皮肤的吸收速率通常是通过使用放射性标记化合物的人体研究来估计的(1)。最近,使用动物(体内或体外)或人类(体外)皮肤来估计皮肤吸收。动物体内经皮吸收通常是通过测量标记化合物局部应用后血液和排泄物中的放射性来确定的。这种间接测定经皮吸收的方法提供了总吸收剂量的估计,但往往不能揭示吸收动力学的信息。迄今为止,确定局部应用化合物的绝对生物利用度的唯一方法是比较局部和静脉给药后血液或尿液中的浓度(2)。由于在这些情况下血液浓度可能非常低,这种做法通常受到测定或分析的敏感性限制。作为放射性示踪剂研究的替代方案,一种新的实时呼吸分析系统与基于生理的药代动力学(PBPK)建模相结合,已被开发出来,用于确定大鼠和人体内的经皮吸收(3)。使用该系统,可以将局部剂量的化合物应用于特定的皮肤表面积,并且呼吸分析系统可用于监测呼出气体中该化合物和/或其代谢物的浓度。PBPK模型,修改以描述皮肤暴露,可以用来确定在各种暴露情况下的皮肤渗透常数。
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引用次数: 5
The development of skin barrier function in the neonate 新生儿皮肤屏障功能的发育
Pub Date : 2001-01-01 DOI: 10.1081/CUS-120001864
Lourdes B. Nonato, Y. Kalia, A. Naik, C. Lund, R. Guy
The skin, one of the largest organs of the body, functions as a protective and regulatory barrier between the body and the external environment. At birth, infants must make the transition from a fluid intrauterine environment to dry, extrauterine life. Full-term infants, born at 40 weeks of gestation, make the transition with a competently formed barrier. However, the skin of the premature neonate comprises as much as 13% of the body weight, compared to only 3% of the body weight of an adult (1). In addition, the surface area to body weight ratio of the neonate is four times that of adults (2). Thus, the immaturity of the skin has numerous ramifications for the neonate, including ineffective thermoregulation (3), fluid imbalance (4), percutaneous absorption of toxins (2), tissue injury (5), infection (6), and delayed healing (7). Within the last decade, new technologies have changed the caretaking practices of the premature neonate; advances in respirator design, monitor technology, reduction of blood volume required for specialized tests, and the sophistication of new diagnostic techniques have all contributed to increasing the chances of survival of the premature neonate (8). Nevertheless, much remains to be learned about the complex extrauterine skin development of these neonates.
皮肤是人体最大的器官之一,是人体与外界环境之间的保护和调节屏障。出生时,婴儿必须从液体的宫内环境过渡到干燥的宫外生活。足月婴儿,在妊娠40周出生,通过一个适当形成的屏障来完成过渡。然而,早产儿的皮肤占体重的13%,而成年人的皮肤只占体重的3%(1)。此外,新生儿的皮肤表面积与体重的比例是成年人的四倍(2)。因此,皮肤的不成熟对新生儿有许多后果,包括无效的体温调节(3)、体液失衡(4)、经皮吸收毒素(2)、组织损伤(5)、感染(6)、和延迟愈合(7)。在过去的十年中,新技术已经改变了早产儿的护理方法;呼吸器设计的进步、监测技术的进步、专门检测所需血容量的减少以及新诊断技术的成熟,都有助于增加早产儿的存活率(8)。然而,关于这些新生儿复杂的子宫外皮肤发育,仍有许多有待了解的地方。
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引用次数: 6
Cutaneous metabolism during in vitro percutaneous absorption 体外经皮吸收过程中的皮肤代谢
Pub Date : 2001-01-01 DOI: 10.1081/CUS-120001860
R. Bronaugh, M. Kraeling, J. Yourick, H. Hood
The skin is a portal of entry and the largest organ of the body. It has been shown to contain the major enzymes found in other tissues of the body (1). Topically applied compounds may be metabolized in skin resulting in altered pharmacologic or toxicologic activity. The metabolism of benzo[a]pyrene applied to mouse skin floating in an organ culture demonstrated the potential importance of metabolism of chemicals during percutaneous absorption (2). A flow-through diffusion cell was subsequently developed to aid in quantitating skin absorption and metabolism (3). Viability of skin in the diffusion cell, which was assessed by light microscopy, was found to be maintained for at least 17 h (3). The viability of pig skin was maintained in flow-through cells by using tissue culture media; skin-mediated hydrolysis of diethyl malonate was observed (4). The suitability of these conditions to maintain skin viability was assessed in initial studies by the ability to graft the skin to nude mice (5).
皮肤是入口,也是人体最大的器官。它已被证明含有在身体其他组织中发现的主要酶(1)。局部应用的化合物可能在皮肤中代谢,从而改变药理学或毒理学活性。将苯并[a]芘的代谢应用于漂浮在器官培养中的小鼠皮肤,证明了化学物质在经皮吸收过程中代谢的潜在重要性(2)。随后开发了一种流动扩散细胞,以帮助定量皮肤吸收和代谢(3)。通过光学显微镜评估扩散细胞中的皮肤活力。发现至少维持了17小时(3)。使用组织培养基在流式细胞中维持了猪皮的活力;观察到皮肤介导的丙二酸二乙酯水解(4)。在最初的研究中,通过将皮肤移植到裸鼠身上的能力,评估了这些条件对维持皮肤活力的适用性(5)。
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引用次数: 11
EFFECT OF HYPOXIC STRESS IN RPE CELLS: INFLUENCE OF ANTIOXIDANT TREATMENTS 缺氧应激对rpe细胞的影响:抗氧化处理的影响
Pub Date : 2001-01-01 DOI: 10.1081/CUS-100000338
J. Bellot, M. Palmero, C. García-Cabanes, M. Sanz, A. Orts
Retinal pigmented epithelium (RPE) is an ocular tissue that performs several important functions such as light perception and phagocytosis. This study investigated the effects of hypoxia and serum and glucose deprivation of the RPE tissue. The possible protective effects of antioxidants were also studied by determining cell viability, ATP content, and DNA fragmentation. The results demonstrate that antioxidants can protect RPE tissue from death through the inhibition of some mechanisms that lead to cellular apoptosis.
视网膜色素上皮(RPE)是一种具有光感知和吞噬等重要功能的眼部组织。本研究探讨了缺氧和血清及葡萄糖剥夺对RPE组织的影响。通过测定细胞活力、ATP含量和DNA片段,研究了抗氧化剂可能的保护作用。结果表明,抗氧化剂可以通过抑制一些导致细胞凋亡的机制来保护RPE组织免于死亡。
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引用次数: 1
The legal distinction in the United States between a cosmetic and a drug 化妆品和药品在美国的法律区别
Pub Date : 2001-01-01 DOI: 10.1081/CUS-120001858
P. Hutt
The Federal Food, Drug, and Cosmetic Act (FD&C Act) establishes substantially different regulatory requirements in the United States for cosmetics and drugs. This chapter traces the history of U.S. regulatory policy for these two categories of products, discusses the application of U.S. law to products that fall within both categories at the same time (i.e., cosmetic drugs), and considers potential strategies for resolving the long-standing concern that the drug provisions of the Act impose overly stringent requirements on cosmetic drugs.
《联邦食品、药品和化妆品法案》(FD&C法案)在美国对化妆品和药品制定了截然不同的监管要求。本章追溯了美国对这两类产品的监管政策的历史,讨论了美国法律对同时属于这两类产品(即美容药物)的应用,并考虑了解决长期存在的担忧的潜在策略,即该法案的药物条款对美容药物施加了过于严格的要求。
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引用次数: 5
PRELIMINARY RESULTS WITH A NEW SOFT PLIABLE DOG INTRAOCULAR IMPLANT: THE CANI/JAG 一种柔软柔韧的新型犬眼内植入物的初步结果:犬/捷格
Pub Date : 2001-01-01 DOI: 10.1081/CUS-100000340
J. Gaiddon, J. Gaiddon, P. Lallement
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引用次数: 0
Percutaneous drug delivery to the hair follicle 经皮给药到毛囊
Pub Date : 2001-01-01 DOI: 10.1081/CUS-120001871
A. Lauer
Unique biochemical and immunological events dictate the complex cyclic growth and differentiation patterns of hair follicles and their associated sebaceous glands (1), structures that are collectively referred to as pilosebaceous units. Once regarded as mere evolutionary remnants, hair follicles and sebaceous glands have been recognized increasingly as significant pathways for percutaneous transport (2). Percutaneous transport routes via the lipoidal domains of the stratum corneum have been well established (3,4), whereas comparatively less is known about the specific roles of hair follicles and sebaceous glands. Determination of the roles of these structures is complicated by the lack of adequate animal models and methodologies that can distinctly distinguish follicular and stratum corneumpathways.Moreover, it may be possible that a topically applied compound traverses more than one pathway simultaneously. The stratum corneum is acknowledged not only as the main barrier to skin penetration, but also as the major permeation pathway. The tightly packed, semicrystalline intercellular lipid domains and the extremely compact corneocytes of the stratum corneum create a barrier highly resistant to percutaneous transport (3,4). Modulation of stratum corneum lipid fluidity by topical agents has been thoroughly studied and is generally acknowledged as the major mechanism of percutaneous delivery (5). Passive percutaneous transport depends on several factors, including penetrant lipophilicity, charge, and molecular size (6). The upper limit of molecular size for permeation through the stratum corneum is still unknown. Early suggestions of a follicular pathway were based on the hypothesis that hair follicles act as shunts, resulting in the rapid transport of ions and large polar molecules. Scheuplein (7) and Scheuplein et al. (8) first described transient follicular delivery for small polar molecules and large polar steroids that ordinarily would not be expected to traverse the skin rapidly due to their charge or restrictive molecular size. Feldmann and Maibach (9) and Maibach et al. (10) observed increases in percutaneous transport through skin areas with greatest follicular densities in both animals and humans, which also hinted at the possibility of follicular delivery.
独特的生化和免疫事件决定了毛囊及其相关皮脂腺复杂的循环生长和分化模式(1),这些结构统称为毛囊皮脂腺单位。毛囊和皮脂腺曾经被认为是进化的残余,但现在越来越多地认识到它们是经皮运输的重要途径(2)。通过角质层脂质结构域的经皮运输途径已经得到了很好的证实(3,4),而对毛囊和皮脂腺的具体作用知之甚少。由于缺乏足够的动物模型和方法来明确区分滤泡和角膜层通路,因此确定这些结构的作用变得复杂。此外,局部施用的化合物可能同时穿过一条以上的途径。角质层不仅是皮肤渗透的主要屏障,也是皮肤渗透的主要途径。紧密堆积的半晶状细胞间脂质结构域和角质层极为致密的角质层细胞形成了高度抵抗经皮运输的屏障(3,4)。外用药物对角质层脂质流动性的调节已经被深入研究,并被普遍认为是经皮给药的主要机制(5)。被动经皮转运取决于几个因素,包括渗透性亲脂性、电荷和分子大小(6)。通过角质层渗透的分子大小上限仍然未知。毛囊通路的早期建议是基于毛囊充当分流器的假设,导致离子和大极性分子的快速运输。Scheuplein(7)和Scheuplein等人(8)首先描述了小极性分子和大极性类固醇的瞬时卵泡递送,由于它们的电荷或限制性分子大小,通常不会期望它们迅速穿过皮肤。Feldmann和Maibach(9)以及Maibach等人(10)观察到,在动物和人类中,通过卵泡密度最大的皮肤区域的经皮运输增加,这也暗示了卵泡分娩的可能性。
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引用次数: 18
期刊
Journal of Toxicology-cutaneous and Ocular Toxicology
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