Dermatological testing

Only a few in vivo dermal toxicity studies have been reported so far. Huczko and Lange [50] evaluated the potential of raw CNTs to induce skin irritation by conducting two routine dermatological tests (patch test on 40 volunteers with allergy susceptibilities and Draize rabbit eye test on four albino rabbits). Koyama etal. [51] showed the biological responses to four different types of carbon nanotubes (SWNTs, two types of MWNTs with different diameters, and cup-stacked carbon nanotubes) after their subcutaneous implantation in mice. Both tests [50, 51] showed no or poor irritation effects. However, the in vitro studies in epidermal cell lines exposed to CNTs, and also a more recent report on the toxic outcomes of topical exposure of mice to SWNTs [46], have raised concerns over these assessments. Clearly, this is an area requiring further scientific evaluation. 

Summary of Tests. Common dermatological tests are shown in Table 20.15 and ophthalmological tests in Table 20.14. Note that any of these tests could be utilized as measures of efficacy if they addressed the clincial trial objectives. Selected pointers are given in Table 20.13. Specific tests that may be used in hematology, clinical chemistry, and urinalysis are shown in Table 20.12, adult and pediatric behavioral rating scales in Tables 20.16 and 20.17, and psychometric and performance tests in Table 20.18. 

Weaver JE (1976) Dermatologic testing of household laundry products a novel fabric softener. Int J Dermatol 15 297-300... 

The regulatory agencies impose certain specific requirements on the formulation and efficacy determination of drags contained in these formulations. For example, the CGMP factors, scale-up and postapproval changes, and dermatological testing for irritation or photosensitivity are some of the specified elements. 

Maibach HI, Akerson JM, Marzulli FN et al. (1980) Test concentrations and vehicles for dermatological testing of cosmetic ingredients. Contact Dermatitis 6 369-404 Majeti VA, Suskind RR (1977) Mechanism of cinnamaldehyde sensitization. Contact Dermatitis 3 16-18... 

Skin tolerance was tested on rabbits. A 1 % alkanesulfonate solution applied five times did not produce any irritation on the rabbits skin. The same results were obtained by the closed patch test carried out with human test subjects in a hospital. The good dermatological properties were also confirmed by the Polano test (arm immersion test). 

In a broad evaluation also the sulfosuccinate disodium laureth sulfosuccinate (DLSS) was a part of a variety of surfactants tested for their dermatological mildness, and some different test methods were applied [16]. Products were compared applying in vitro methods (Zein test, hemolysis) and in vivo methods (Duhring-Chamber test, skin mildness by intracutaneous test on mice and topical application on hairless mice, mucous membrane irritation according to the Draize procedure on rabbit eyes). In the Duhring-Chamber test the DLSS elicited no reactions in the animal tests it ranged in the least irritant third of the 15 products tested. 

Arnold AW, Hausermann P, Bach S, Bircher AJ Recurrent flexural exanthema (SDRIFE or baboon syndrome) after administration of two different iodinated radiocontrast media. Dermatology 2007 214 89-93. Laroche D Immediate reactions to contrast media mediator release and value of diagnostic testing. Toxicology 2005 209 193-194. 

Adverse reactions CNS Convulsions, confusion, drowsiness, myoclonus, fever Dermatologic Rash Metabolic Electrolyte imbalance Hematologic Positive Coombs test, hemolytic anemia Local Rain, thrombophlebitis Renal Acute interstitial nephritis Miscellaneous Anaphylaxis, hypersensitivity, Jarisch-Herxheimer reaction CNS Seizures, confusion, drowsiness, myoclonus, CNS stimulation Cardiovascular Myocardial depression, vasodilation, conduction disturbances Hematologic Positive Coombs test, hemolytic anemia, neutropenia Local Thrombophlebitis, sterile abscess at injection site Renal Interstitial nephritis Miscellaneous Pseudoanaphylactic reactions, hypersensitivity, Jarisch-Herxheimer reaction, serum sickness... 

V. P. Shah, J. S. Elkins, and R. L. Williams, Evaluation of the test system used for in vitro release of drugs for topical dermatological drug products, Pharm. Dev. Tech., 4, 377 (1999). 

Dermatologic findings with erythema nodosum, pyoderma gangrenosum, or aphthous ulceration Laboratory tests... 

Chemistry0 Hematologic Tests0 Metabolic Tests" Tests Tests Tests Serum Electrolytes9 Dermatologic ... 

A few selected safety measurements and tests for specialized dermatological examination are listed in Table 20.15. 

TABLE 20.15. Selected Examples of Safety Measurements and Tests for a Specialized Dermatological Examination... 

Berardesca E, Herbst R, Maibach H. 1993. Plastic occlusion stress test as a model to investigate the effects of skin delipidization on the stratum comeum water holding capacity in vivo. Dermatology 187 91-94. 

Ora/-Adverse reactions requiring discontinuation include Pulmonary infiltrates or fibrosis paroxysmal ventricular tachycardia CHF elevation of liver enzymes visual disturbances solar dermatitis blue discoloration of skin hyperthyroidism hypothyroidism. Adverse reactions occurring in at least 3% of patients include CFIF Gl complaints (nausea, vomiting, constipation, anorexia) dermatologic reactions (photosensitivity, solar dermatitis) neurologic problems (malaise, fatigue, tremor/abnormal involuntary movements, lack of coordination, abnormal gait/ataxia, dizziness, paresthesias) abnormal liver function tests. 

Voss W, Dermatest GmbH, Munster, Germany (2004) Special dermatological Report on a Sensitization Test According to Magnussen (Repetitive Epicutaneous Test)... 

Urea is a normal physiological metabolite and is generally regarded as nontoxic. No report on sensitization has been found, despite its wide use in dermatological preparations. In 1943, Rattner patch tested 500 hospital patients, 66 of whom had skin disease, with a 3% urea cream and found no adverse reaction.4 Clinical and patient assessments of the use of creams with 10% urea or lower give no evidence of skin irritation with inflammation and barrier damage,38 although occlusive exposure... 

Petrolatum continues to be used quite extensively in dermatological applications, primarily for three purposes (1) as an inert patch testing base, (2) as a vehicle in the dermal application of pharmaceuticals, and (3) as a treatment product itself. 

Petrolatum is widely used as a classic skin moisturizer.110 Its uses range from cosmetic skin care products to dermatological treatments to patch test substrates to tissue paper emollients. As long as people require soft, supple, moisturized skin, petrolatum will be a key ingredient in meeting that requirement. 

Pierard, G.E. and Pierard-Franchimont, C. Dihydroxyacetone test as a substitute for the dansyl chloride test. Dermatology 186, 133-137 (1993). 

Tumjamaa, K., Darsow, U., Niggemann, B. et al. 2006. EAACI/GA2 LEN Position Paper Present status of the atopy patch tests. Position paper of the Section on Dermatology and the section on Pediatrics of the European Academy of Allergy and Clinical Immunology. Allergy 61 1377-1384. 

This test using animals seems to be the most frequently used predictive test for the identification of skin-sensitizing chemicals or for chemicals prone to cause allergic contact dermatitis. While it is most frequently used for general dermatological investigations, results... 

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