International Journal of Dental Science and Innovative Research (IJDSIR) is a Online version cum Open-Access publisher of journals & books covering a wide range of academic disciplines. Our goal is to bring high quality research work. IJDSIR Provide dental journal, dental science, Indian dental Journal, Journal of Dental Sciences, Journal of Research in Medical and Dental Science Thesis/Dissertation Submission: July 5: University Holiday for Independence Day: August Classes End: Registration Dates. Registration for summer begins March 2, Change of Schedule. Students may change their summer schedule via Web Registration or in the lobby of John Hubbard Hall. Schedule changes can be made according to the Specialist training: Master of Medicine. This programme trains medical doctors to become specialists in one of a range of disciplines. Training takes place over a minimum period of four years, full-time, and in some cases more, to allow the student to complete the dissertation
Safety evaluation of topical applications of ethanol on the skin and inside the oral cavity
Try out PMC Labs and tell us what you think. Learn More. Ethanol is widely used in all kinds of products with direct exposure to the human skin e. medicinal products like hand disinfectants in occupational settings, cosmetics like hairsprays or mouthwashes, pharmaceutical preparations, and many household products, dissertation in oral medicine and radiology.
Contradictory evidence about the safety of such topical applications of the alcohol can be found in the scientific literature, yet an up-to-date risk assessment of ethanol application on the skin and inside the oral cavity is currently lacking.
The first and foremost concerns of topical ethanol applications for public health are its carcinogenic effects, as there is unambiguous evidence for the carcinogenicity of ethanol orally consumed in the form of alcoholic beverages. So far there is a lack of evidence to associate topical ethanol use with an increased risk of skin cancer.
Limited and conflicting epidemiological evidence is available on the link between the use of ethanol in the oral cavity in the form of mouthwashes or mouthrinses and oral cancer. Some studies pointed to an increased risk of oral cancer due to locally produced acetaldehyde, operating via a similar mechanism to that found after alcoholic beverage ingestion.
In addition, topically applied ethanol acts as a skin penetration enhancer and may facilitate the transdermal absorption of xenobiotics e. carcinogenic contaminants in cosmetic formulations. Ethanol use is associated with skin irritation or contact dermatitis, especially in humans with an aldehyde dehydrogenase ALDH deficiency, dissertation in oral medicine and radiology.
After regular application of ethanol on the skin e. in the form of hand disinfectants relatively low but measurable blood concentrations of ethanol and its metabolite acetaldehyde may occur, which are, however, below acute toxic levels. Only in children, especially through lacerated skin, can percutaneous toxicity occur. As there might be industry bias in many studies about the safety of topical ethanol applications, as well as a general lack of scientific research on the long-term effects, there is a requirement for independent studies on this topic.
The research focus should be set on the chronic toxic effects of ethanol and acetaldehyde at the point of impact, with special regard to children and individuals with genetic deficiencies in ethanol metabolism. Ethanol is widely used as a solvent dissertation in oral medicine and radiology in the home and in industry [ 1 ].
Consumers may be exposed to ethanol from its application as a constituent of many household and personal products, such as cosmetics, hairsprays, window cleaners, de-icers and certain pharmaceutical preparations [ 2 ]. Most people have experienced skin contact with alcoholic solutions [ 1 ]. The safety of topical applications of ethanol is still a matter of debate, and there appears to be scientific evidence pointing in both directions.
On the one hand, researchers came to the conclusion that the range of damage caused to the skin by the alcohol cannot and should not be ignored, although the deleterious effects of ethanol exposure on the skin may pale into insignificance compared to its effects on the liver, central nervous system, and other body systems after ingestion [ 3 ]. On the other hand, scientific studies attributed ethanol for topical uses as safe per se [ 14 - 7 ]. However, there appears to be at least some evidence, including epidemiological data, about mouthwash use, and data from animal experiments showing that ethanol on the skin or inside the oral cavity may cause harm if used chronically.
Evaluation according to EU cosmetics legislation [ 8 ] and other acts about chemical safety should consider the chronic toxic and carcinogenic potential of ethanol. In this article, the safety of topical uses of ethanol will be evaluated by a critical review of the scientific literature.
Searches in both English and German were carried out in Julyin the following databases: PubMed, Toxnet and ChemIDplus U. This was accompanied by a hand search of the reference lists of all articles for any relevant studies not included in the databases. The references, including abstracts, were imported into Reference Manager V. Most research on ethanol is centred around its effects after ingestion in the form of alcoholic beverages, which is a major risk factor for the burden of disease in our society [ 9 ].
Significantly less information is available on dissertation in oral medicine and radiology effects of ethanol if topically used on human skin or in the oral cavity. Our discussion will begin with the mechanisms of toxicity known from ethanol ingestion, for which there is evidence that they could also apply to topical ethanol use i. carcinogenicity and local effects of ethanol on the human skin, dissertation in oral medicine and radiology. After that, the effects of ethanol as a skin penetration enhancer will be discussed, which are excellently described from pharmaceutical applications.
Finally, certain groups of products are discussed in detail cosmetics, mouthwashes, and hand disinfectantsand an overall risk assessment is provided, dissertation in oral medicine and radiology. The recent evaluation of ethanol in alcoholic beverages as 'carcinogenic to humans' must be considered in the risk assessment of topical application forms. This paragraph summarizes the scientific proof for this association, which has been primarily derived from epidemiological studies about the ingestion of alcoholic beverages.
In Februarythe WHO's International Agency for Research on Cancer IARC re-assessed the carcinogenicity of alcoholic beverages in the context of the IARC monographs programme.
Overall, the IARC concluded that the occurrence of malignant tumors of the oral cavity, pharynx, larynx, esophagus, liver, colorectum, and female breast is causally related to alcohol consumption [ 11 ], dissertation in oral medicine and radiology. Because the associations were generally noted with different types of alcoholic beverages, and in view of the carcinogenicity of ethanol in animals, the IARC now considers ethanol itself not dissertation in oral medicine and radiology constituents or contaminants as causative of the carcinogenicity of alcoholic beverages.
Many studies dissertation in oral medicine and radiology different design and in different populations around the world have consistently shown that regular alcohol consumption is associated with an increased risk of cancers of the oral cavity, pharynx, larynx, and esophagus [ 12 ].
Daily consumption of around 50 g of alcohol ethanol increases the risk of these cancers by two to three times compared to non-drinkers [ 1113 - 15 ]. Furthermore, in populations that are deficient in the activity of aldehyde dehydrogenase, an enzyme involved in the catabolism of ethanol, much higher risks for oesophageal cancer after alcohol consumption have been reported than in populations with a fully active enzyme [ 16 ].
This is also proof that acetaldehyde derived from ethanol metabolism contributes to its carcinogenicity. Results of animal experiments have confirmed the carcinogenicity of acetaldehyde and ethanol [ 11 ].
During topical-application of ethanol, the most prone organ for adverse effects appears to be the skin, which comes into direct contact with the agent. The second organ that may be regularly exposed to topical ethanol is the oral cavity through use of alcohol-containing mouthwashes or mouthrinses. In their evaluation of the carcinogenicity of alcoholic beverages and ethanol, the IARC also appreciated the association between melanoma and alcohol consumption [ 10 ]. The IARC considered two cohort studies, one in an occupational group exposed to ionizing radiation and one in alcoholic women.
Dissertation in oral medicine and radiology the cohort study of radiologic technologists in the U. and in the study of alcoholic women in Sweden, no significant associations were seen [ 1718 ]. Furthermore, a number of case-control studies published results on melanoma risk in relation to alcohol intake.
Some of those studies reported no significant association between alcohol intake and melanoma risk [ 19 - 23 ]. Whereas, three case-control studies in the U. reported some increase in risk of melanoma associated with alcohol intake [ 24 - 26 ]. None of these were adjusted for exposure to UV light, and thus the possibility of confounding cannot be excluded. The IARC concluded that melanoma is not one of the cancer sites with a clear association with ethanol consumption.
Besides melanoma, a few studies have linked alcohol consumption to a higher risk of basal cell carcinoma [ 27dissertation in oral medicine and radiology, 28 ]. Only a few studies have suggested potential biological mechanisms for a possible relationship between alcohol and melanoma risk [ 17 ].
The high-risk behaviour of binge and heavy drinking may be associated with higher rates of sunburn, dissertation in oral medicine and radiology, which may lead to skin cancer [ 29 ].
A pituitary-mediated mechanism has been proposed as a direct effect of ethanol [ 3031 ]. Another hypothesis on the aetiology of alcohol induced melanoma is an altered redox state caused by alcohol metabolism [ 32 ], dissertation in oral medicine and radiology. Ethanol ingestion may also lead to a decrease of carotenoid antioxidant substances in the skin, which then causes erythema to occur faster and with greater intensity following UV irradiation [ 33 ]. Interesting evidence into the induction of melanoma and non-melanoma skin cancers is provided by the animal experiments of Strickland et al.
The studies suggest that the interaction of topically applied compounds like ethanol and Aloe emodin a trihydroxyanthraquinone found in Aloe barbadensismay be, in conjunction with UV radiation, important in causing melanin-containing tumours. As an underlying mechanism the authors speculated that the anaerobic flora of the pilosebaceous unit transforms ethanol to acetaldehyde and thus fosters ethanol-based carcinogenesis. The authors found that their research may pose public health implications due to the presence of these compounds in consumer products, especially the simultaneous use of ethanol and the gel of Aloe barbadensiswhich forms the basis of a large number of skin care products, under exposure of UV light.
However, it remained undetermined if dissertation in oral medicine and radiology results from animal experiments dissertation in oral medicine and radiology be transferable to humans. All in all, it can be concluded that there is a lack of evidence to associate topical ethanol use with an increased risk of skin cancer.
However, the carcinogenic properties of ethanol must be regarded in the risk assessment of such products anyway, dissertation in oral medicine and radiology, because ethanol may be transported by the blood stream to more susceptible organs after skin penetration see below. The synergistic effects with Aloe barbadensis show that each formulation of an ethanol containing product must be thoroughly evaluated for its carcinogenic potential.
Besides skin cancer, alcohol abuse has been associated with the development of several skin disorders including psoriasis, discoid eczema and superficial infections [ 37 - 40 ]. Chronic alcohol abuse is also a predisposing factor for necrotizing wound infections, delayed wound healing and cellulitis [ 41 ]. There are several theories about the causes for such skin diseases including immune suppression, mal-nutrition, liver disease [ 42 ] or the influence of alcohol on lipid metabolism [ 43 ], dissertation in oral medicine and radiology.
As acute and chronic alcohol abuse modulate immunity [ 44 ], this mechanism can explain dermatological diseases, which have an immune pathogenetic mechanism [ dissertation in oral medicine and radiology ].
However, there are only a few studies about the molecular mechanisms of alcoholic skin diseases. Farkas et al. An interesting patch test was conducted by Haddock et al. No erythema were observed from patch tests with ethanol on non-hydrated skin, while all applications of acetaldehyde resulted in notable erythema. Using the same test on hydrated skin i. immersion of the test site in water for 10 min before application of the patcheslocalized erythema were also caused by ethanol.
The reactions were judged to represent a direct pharmacologic action of topical alcohols on the cutaneous microvasculature, and that erythemogenesis is enhanced after hydration because of an increase in cutaneous permeability to alcohol.
Höök-Nikanne et al. The authors concluded that this primary observation of bacterial production of acetaldehyde could offer an explanation for the deleterious effect of alcohol on various skin diseases, and that these preliminary results warranted further in vivo study.
However, to our knowledge no further studies into this mechanism were conducted. This research would be extremely important, as the formation of acetaldehyde either by bacteria strains on the human skin or by metabolism following absorption is also a likely mechanism in topically applied products. However, the amount of acetaldehyde formation after topical application of ethanol on intact, healthy skin is currently unknown. The bacterial acetaldehyde production may be restricted as both the transient and resident microorganisms may be significantly reduced by the ethanol application, which should lead to higher local ethanol concentrations as in the case of systemic distribution after alcohol ingestion.
In addition, the contact time should be shorter in the case of topical ethanol application dissertation in oral medicine and radiology of the fast evaporation of the alcohol, dissertation in oral medicine and radiology. Systematic in vitro and in vivo studies have elucidated the mechanism of percutaneous alcohol absorption [ 149 - 62 ]. Numerous data are available on permeability, partition coefficients and diffusion constants.
It is now generally accepted that the "barrier" function of the skin resides almost entirely in the stratum corneum [ 53556364 ].
Most water-soluble, low-molecular weight non-electrolytes — among them ethanol — applied to the skin surface can diffuse much faster into the blood-stream if the epidermis is diseased, damaged or removed [ 63 ].
Ethanol is also well known as a topical penetration enhancer and may be used in transdermal delivery systems [ 65 - 81 ]. Bommannan et al. This lipid extraction may lower the skin barrier function and render the membrane more permeable, which is the most likely explanation for dissertation in oral medicine and radiology effect of ethanol as a skin penetration enhancer. Kai et al. Goates et al. The mechanism of ethanol as a skin permeation enhancer was described to be a so-called 'pull' or 'drag' effect, which means that the permeation of the enhancer subsequently facilitates that of the solute in the sense of a simple co-permeation [ 7980 ].
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