Is there tissue penetration after application of topical salicylate formulations?

Cross, Sheree E.; Anderson, Chris; Thompson, Melanie J.; Roberts, Michael S.

doi:10.1016/s0140-6736(05)63324-7

Cited by 43 publications

(16 citation statements)

References 4 publications

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“…Methyl salicylate is known to absorb easily and rapidly through skin, 33 which is one of the reasons why it is used in topical analgesic and anti-inflammatory ointments or liniments. It is hydrolysed in the body principally to salicylic acid.…”

Section: Analytical Proceduresmentioning

confidence: 99%

Site‐specific percutaneous absorption of methyl salicylate and VX in domestic swine

Duncan¹,

Brown²,

Lundy³

et al. 2002

J of Applied Toxicology

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The site specificity of the percutaneous absorption of methyl salicylate (MeS) and the organophosphate nerve agent VX (O-ethyl S-(2-diisopropylaminoethyl) methylphosphonothioate) was examined in anaesthetized domestic swine that were fully instrumented for physiological endpoints. Four different anatomical sites (ear, perineum, inguinal crease and epigastrium) were exposed to the MeS and the serum levels were measured over a 6-h time period. The dose absorbed at the ear region was 11 microg cm(-2) with an initial flux of 0.063 microg cm(-2)min(-1), whereas at the epigastrium region the dose absorbed was 3 microg cm(-2) with an initial flux of 0.025 microg cm(-2)min(-1). For this reason further studies were carried out with VX on the ear and the epigastrium only. In animals treated with agent on the epigastrium, blood cholinesterase (ChE) activity began to drop 90 min after application and continued to decline at a constant rate for the remainder of the experiment to ca. 25% of awake control activity. At this time there were negligible signs of poisoning and the medical prognosis was judged to be good. In contrast, the ChE activity in animals receiving VX on the ear decreased to 25% of awake control values within 45 min and levelled out at 5-6% by 120 min. Clinical signs of VX poisoning paralleled the ChE inhibition, progressing in severity over the duration of the exposure. It was judged that these animals would not survive. The dramatic site dependence of agent absorption leading to vastly different toxicological endpoints demonstrated in this model system has important ramifications for chemical protective suit development, threat assessment, medical countermeasures and contamination control protocols.

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Section: Analytical Proceduresmentioning

confidence: 99%

Site‐specific percutaneous absorption of methyl salicylate and VX in domestic swine

Duncan¹,

Brown²,

Lundy³

et al. 2002

J of Applied Toxicology

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“…6,7,10,16 Similarly, diclofenac has been measured in synovial fluid collected from the knee joints of humans, 3,4 although the mechanism by which it got there is unclear. Penetration of topically applied SA formulations into underlying muscle has been reported elsewhere.…”

Section: Discussionmentioning

confidence: 99%

Penetration of a topically applied nonsteroidal anti-inflammatory drug into local tissues and synovial fluid of dogs

Mills¹,

Magnusson²,

Cross³

2005

ajvr

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“…However, skin is also a metabolically competent organ. The first-pass effect of the skin has largely been neglected even though the metabolism of many compounds has been highlighted (e.g., parabens, 35 methyl salicylate, 36 benzo[a]-pyrene 37 ). Some chemicals are absorbed across the skin and metabolized into active compounds.…”

Section: Skin Metabolismmentioning

confidence: 99%

Review of the Availability ofIn VitroandIn SilicoMethods for Assessing Dermal Bioavailability

DumontCoralie

PrietoPilar

AsturiolDavid

et al. 2015

Applied In Vitro Toxicology

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The exposure of the skin to consumer products, drugs, and environmental chemicals can result in their penetrating the skin barrier and entering systemic circulation, potentially resulting in adverse effects in the skin and other organs. The assessment of dermal penetration and bioavailability (including penetration, metabolism, and entry into the systemic circulation) is therefore an important consideration in the risk assessment of chemicals. The skin is a heterogeneous organ with a multilayer structure. Based on its architecture and physiology, substances can penetrate through three major ways but can also be blocked in the different skin layers and in the skin appendages, which act as reservoir. In addition to that, as the skin is a metabolically competent organ, substances can undergo metabolism. After a brief description of the skin architecture, this review will focus on the skin penetration mechanisms and skin metabolic capacities. The skin absorption has traditionally been tested in vivo on animals. However, with the new legislation (i.e., Registration, Evaluation, Authorisation, and Restriction of Chemicals Regulation or Cosmetics Regulation), alternatives to animal testing have to be implemented. In a second part, this review will provide a description of the main in vitro and in silico or computational models available to study skin absorption and skin metabolism (i.e., ex vivo skin models, artificial membrane barriers, primary cells and cell lines, Quantitative Structure-Activity Relationship [QSAR], simulators for the prediction of skin metabolism).

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Is there tissue penetration after application of topical salicylate formulations?

Cited by 43 publications

References 4 publications

Site‐specific percutaneous absorption of methyl salicylate and VX in domestic swine

Site‐specific percutaneous absorption of methyl salicylate and VX in domestic swine

Penetration of a topically applied nonsteroidal anti-inflammatory drug into local tissues and synovial fluid of dogs

Review of the Availability ofIn VitroandIn SilicoMethods for Assessing Dermal Bioavailability

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