Dermal preparations irritation

SAFETY PROFILE Experimental teratogenic and reproductive effects. Questionable carcinogen with experimental carcinogenic and tumorigenic data. Mutation data reported. Used in pharmaceutical and dermal preparations as an emulsifying agent. When heated to decomposition it emits acrid smoke and irritating fumes. 

Health and Safety Factors. Animal-feeding studies of DMPPO itself have shown it to be nontoxic on ingestion. The solvents, catalyst, and monomers that are used to prepare the polymers, however, should be handled with caution. Eor example, for the preparation of DMPPO, the amines used as part of the catalyst are flammable toxic on ingestion, absorption, and inhalation and are also severe skin and respiratory irritants (see Amines). Toluene, a solvent for DMPPO, is not a highly toxic material in inhalation testing the TLV (71) is set at 375 mg/m, and the lowest toxic concentration is reported to be 100—200 ppm (72). Toxicity of 2,6-dimethylphenol is typical of alkylphenols (qv), eg, for mice, the acute dermal toxicity is LD q, 4000 mg/kg, whereas the acute oral toxicity is LD q, 980 mg/kg (73). The Noryl blends of DMPPO and polystyrene have PDA approval for reuse food apphcations. 

The chemical to be tested is applied in a single dose to the skin of several animals, each animal serving as its own control. The degree of irritation is recorded and scored at specified intervals, and further described to provide a complete evaluation of the chemical toxicity. The study duration should be long enough to fully evaluate the reversibility (or irreversibility) of the effects observed in the animals. The test chemical should be prepared as indicated for acute dermal toxicity test. However, strongly acidic or alkaline chemicals, (e.g., with a demonstrated pH of 2 or less or 11.5 or greater) need not be tested for dermal irritation, because of their predictable corrosive properties. 

Liquid preparations intended for dermal application contain the largest variety of cosolvents. They most commonly include ethanol, isopropanol, propylene glycol, glycerin, and PEG 400. Irritation and sensitization are important considerations in choosing a cosolvent for dermal use. In addition, it may be necessary to... 

The depth of skin necrosis is directly proportional to the concentration of the TCA. Necrosis should not be the only endpoint of a TCA peel - stimulation also plays an important role. Repeated application of less concentrated TCA helps rebuild the papillary dermis directly and/or indirectly as a result of the repeated dermal irritation of the peel-induced inflammation. It is possible to reach the dermis using a low-concentration solution apphed to an epidermis that has been made temporarily more permeable by a prior peel or robust preparation. 

In New Zealand white rabbits, patches soaked with 0.5 mL of undiluted 2-butoxyethanol acetate were applied to one site of the prepared skin surface (Jacobs et al. 1989). The untreated skin was used as a control. Erythema scores were obtained 1, 24, 48, and 72 hours after application of the undiluted substance for 4 hours. The erythema scores of exposure to 100% 2-butoxyethanol acetate for 4 hours in rabbits showed a ranking of 2, which is the minimal mean erythema needed to classify substances as skin irritants. New Zealand rabbits exposed dermally to unspecified doses of 2-butoxyethanol acetate for 24 hours exhibited dermal effects (Truhaut et al. 1979). When 2-butoxyethanol acetate was tested for primary irritation of the skin, four of six rabbits showed slight erythema (grade 1) at 24 hours. Dermal irritation from exposure to 2-butoxyethanol acetate has been studied in rabbits using both the Draize protocol (24-hour occluded exposure) and the European Economic Communities protocol (4-hour occluded exposure) (Zissu 1995). For both protocols, 0.5 mL of undiluted 2-butoxyethanol acetate was placed on the skin. 2-Butoxyethanol acetate was considered a moderate irritant by the Draize protocol and non-irritating by the European Economic Communities protocol. 

The cosmetics and transdermal drug delivery fields are also expected to further benefit from the formulation of microemulsions from mild sugarbased surfactants. Lehmann et al. have studied the effect of such a microemulsion on dermal and corneal irritation, and hydrocortisone incorporation [105]. A microemulsion containing commercially available sucrose esters, isopropyl myristate, and propylene glycol and water was prepared as a water continuous system, and 16.5% hydrocortisone was loaded into the anhydrous base mixture. The formulation spread well on the skin due to the low surface tension of the system at 26 mN/m. While the microemulsion provided greater drug penetration, it also resulted in irritation and barrier compromise. The authors make the point that the formulation may be better suited to drugs that do not induce an irritation themselves. 

Diacyl lysine anionic surfactants, A -octanoyl-A -octanoyl lysine with different counterions (lysine, Na, K, Li) (Figure 5.4, 1 R = -ONa+, -OLysine+, -OK+, -OLi+) showed less cytotoxicity than sodium dodecyl sulfate (SDS). Moreover, they were less eye-irritating than SDS and none showed phototoxic effects. These surfactants are a promising alternative to commercial anionic surfactants given their low ocular and dermal irritancy. These properties offer great potential for topical preparations [66]. 

Non-crosslinked HA may also be used for skin biorevitalisation, a process of inducing fibroblast stimulation and regeneration of the intracellular components that support the dermis Biorevitalisation with HA is different from applications of HA as a filler. Although both procedures provide a reduction in skin wrinkles and folds biorevitalisation can also provide skin rehydration, treat skin irritation, reduce muscle tone of the face and neck, correct skin sagging of the abdomen, inner thighs and upper arms, reduce wrinkles around the eyes, chest and upper lip, as well as remove the dark circles around the eyes and shrink enlarged oily skin pores. This treatment provides reduction in skin wrinkles and dermal folds and is used for skin preparation prior to chemical peels or laser treatments [20-26]. 

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