Standardization of the TRUE Test imidazolidinyl urea and diazolidinyl urea patches.

The preservatives imidazolidinyl urea (IMID, Germall 115) and diazolidinyl urea (DU, Germall II) are commonly used in cosmetic products and are well-known sensitizers. The aim of the present study was to establish the optimal patch test concentration in hydrophilic dried-in vehicle (TRUE Test) for IMID and DU. 181 patients were included in the study. Of these, 150 were patients referred for patch testing, 12 were patients with known allergy to IMID and 19 were patients with known allergy to DU. 76 consecutive patients and the 12 IMID-allergic patients were patch tested with a dilution series IMID (0 to 600 microg/cm(2)), formaldehyde (180 microg/cm(2)) and DU (200 microg/cm(2)). 74 consecutive patients and the 19 DU-allergic patients were patch tested with a dilution series of DU (0 to 600 microg/cm(2)), formaldehyde (180 microg/cm) and IMID (200 microg/cm(2)). A positive dose-response relationship was found. The number of doubtful reactions decreased with increasing test concentrations. No late reactions were observed. A patch test concentration in hydrophilic dried-in vehicle (TRUE Test) of 600 microg/cm(2) was found to be adequate and safe for both IMID and DU.

Tixocortol pivalate contact allergy in the GPMT: frequency and cross-reactivity.

In spite of their intrinsic anti-inflammatory properties, corticosteroids can induce contact allergy. When studying the allergenic properties of corticosteroids it has to be considered that both the allergenic and anti-inflammatory effect may influence the induction phase as well as the elicitation phase and that such effects may be dose-dependent. A multiple dose guinea pig maximization test (GPMT) was therefore used to study the dose-response relationship of tixocortol pivalate. The GPMT was conducted according to OECD guideline #406, using a multiple-dose design and test results were analysed with logistic regression analysis. There was a significant tixocortol pivalate sensitization of the test animals compared to the control group (p<0.05), after both challenge and re-challenge. The challenge with 1% tixocortol pivalate gave more positive reactions than the challenge with 3%. The highest frequency of positive animals was observed when the animals were treated with low to intermediate induction concentrations and intermediate to high challenge concentrations with tixocortol pivalate in the TRUE Test. Cross-reactivity was found between tixocortol pivalate and hydrocortisone, which was expected from their close molecular resemblance, whereas no cross-reactivity was seen between tixocortol pivalate and the 3 other corticosteroids: amcinonide, budesonide, and hydrocortisone-17-butyrate.

Evaluation of Göttingen minipig skin for transdermal in vitro permeation studies.

The optimal skin type for in vitro permeability studies depends on the purpose of the specific transdermal study. In a number of cases, it may be advantageous to use animal skin as an alternative to human skin although they have different characteristics. Recently, Göttingen minipigs have been reported as good models in toxicological and pharmacokinetic studies of drug substances. In this paper, the potential use of skin from the Göttingen minipig is evaluated by studying three model drug substances (nicotine, salicylic acid and testosterone) through skin from humans, domestic pigs and three ages of the Göttingen minipig. An analysis of variance and a Student's t-test showed that both the skin from the Göttingen minipig and the domestic pig possessed transdermal permeabilities, which correlated with human skin and exhibited a lower intra- and intervariation. Furthermore, it was shown that permeability and variation of fluxes through skin from Göttingen minipigs were dependent on the age of the minipig and of the drug substance. It is concluded that the Göttingen minipig, like the domestic pig, is a good skin model for in vitro permeation through human skin.