Clinical evaluation of anaesthetic-like effect of two dermocosmetic formulations containing Aquaphilus dolomiae extract-G3 in subjects with sensitive facial skin.

BACKGROUND: Sensitive skin is a common condition of hyper-reactivity to external stimuli, e.g. heat or abrasion. The symptoms are subjective but can be measured using validated emotional and technical methods. Avène water has several beneficial effects on the skin. In vitro studies indicated that the active component of this natural spring water, Aquaphilus dolomiae extract-G3 (ADE-G3), modulates cutaneous sensitivity via an anaesthetic-like mechanism. OBJECTIVES: To assess facial skin reactivity after repeated application of two formulations containing ADE-G3. METHODS: In open-label studies, healthy subjects with sensitive facial skin applied cream or balm twice daily for 84 days. The severity of skin sensitivity was measured using the Sensitive Scale (based on quantifying visible or subjective signs). Subjective responses associated with pain or uncomfortable feeling were assessed by measuring electrodermal response (EDR). This involves measuring variations in skin electrical resistance due to non-conscious physiological changes in activity of the sympathetic nervous system. Subjects were also evaluated for beneficial effects according to a quantitative approach using semantic assessment of a question regarding their skin quality. Evaluations were performed before and after the first application, and after 29/30, 56 and 84 days of twice daily use. RESULTS: There was a significant decrease in the EDR after stimuli immediately after the application of both ADE-G3 formulations, which continued to decrease over 84 days (40-50% decrease by D85). Likewise, all physical and functional signs of the Sensitive Scale were significantly decreased immediately after the first application and at all time points tested after treatment. Verbatim analysis revealed a semantic shift, from mainly negative terms on D1 to mainly positive terms at D85 for both tested products. CONCLUSIONS: These results demonstrated that two formulations containing ADE-G3 reduced skin sensitivity, indicating a decreased activation of the sympathetic nervous system associated with this condition.

Development and evaluation of an HPLC urinalysis screening test for occupational exposure to 3,4- and 3,5-dichloroanilines.

OBJECTIVE: In order to develop a screening test to detect human occupational exposure to aromatic amines such as 3,4-dichloroaniline (3,4-DCA) and 3,5-dichloroaniline (3,5-DCA), we first investigated the urinary excretion of these highly toxic compounds in the rat. The study was performed after both oral and dermal application, even though contact with the skin is the major route of contamination in the workplace. The aim of this study was to develop a rapid screening test for risk assessment in the workplace. METHODS: An initial group of 3 rats was treated with 40 microl of 3,4-DCA solution (30% in methanol), applied topically to the shaved dorsal skin. A second group of 3 rats were administered the same dose of the amine orally by gavage before urine sampling. The same procedure was performed with 3,5-DCA (2 other groups of 3 rats). The urine samples were collected for a period of 24 hours after treatment and the excretion of 3,4-DCA, 3,5-DCA was studied using a GC-MS and an HPLC method after urine extraction. The urine of 2 workers potentially exposed to the amines for a period of 161 and 147 days, respectively, was analyzed by the same methods with urine collection before and at the end of the work shift. RESULTS: The study of excretion in the rat showed that unchanged dichloroanilines and some metabolites were excreted 24 hours after administration of the amines. Based on these results, we propose an HPLC method for the screening of risk assessment in the workplace. The presence of 3,4-DCA and 3,5-DCA in the urine of workers showed that they were absorbing amines during the workshift. CONCLUSIONS: These results successfully allowed us to detect contamination due to 3,4-DCA and 3,5-DCA in exposed workers. The HPLC method described provides a satisfactory and sensitive procedure for urine screening in the assessment and monitoring of the occupational exposure to dichloroanilines.

In vivo study of percutaneous absorption of 4-chloroaniline using microdialysis in the rat.

The present work was undertaken to study the percutaneous absorption of 4-chloroaniline (parachloroaniline, PCPA, CAS 106-47-8), a chemical intermediate in pesticide manufacture, using in vivo microdialysis in the rat. The results of the microdialysis study showed that PCPA was able to cross the skin (Tmax = 3 h and area under the curve (AUC) = 332.1 ng.h/ml) and rapidly enter the systemic circulation (Tmax = 3.3 +/- 0.6 h). It could be also shown that PCPA was partly metabolised during its percutaneous absorption. The analysis of cutaneous dialysate samples using gas chromatography/mass spectrometry (GC-MS) showed that the metabolite was 4-chloracetanilide. Taken together, the data obtained showed that contact with the skin is a danger for exposed persons.

In vitro study of the percutaneous absorption of four aromatic amines using hairless rat skin.

Using hairless rat skin maintained in a Franz diffusion cell, the percutaneous penetration of four aromatic amines: para-chloroaniline (PCPA), meta-trifluoromethylaniline (mTFMA), dichloro-3,4-aniline (3,4-DCA) and dichloro-3,5-aniline (3,5-DCA) were studied. The purpose of the studies was to determine the permeation parameters (rate of permeation, permeability rat constant) in order to compare the rate of absorption of the four amines. The results show that the four amines penetrate significantly across the skin, but with different rates. 10 h after in vitro application (2 mg/cm2), the extent of permeation was PCPA >> mTFMA > 3,4-DCA > 3,5-DCA.