B Gruvberger

Stability of corticosteroid patch test preparations.

This study investigated the stability of tixocortol pivalate, budesonide, and hydrocortisone‐17‐butyrate (Hc‐17‐B) when present in a mix with petrolatum and when the corticosteroids were kept separately in petrolatum. The concentrations chosen for the corticosteroids were the same as those used in a study within the European Environmental Contact Dermatitis Research Group (EECDRG), in which 2 corticosteroid mixes (1 with a high concentration and 1 with a low concentration) and the 3 individual constituents, each at 2 concentrations, were patch tested. Ethanolic solutions of each corticosteroid, as well as 2 mixtures of these 3 corticosteroids, were also made up at corresponding concentrations. The preparations were kept at room temperature, refrigerated, and deep frozen, and repeatedly for 1 year, investigations to check stability by high performance liquid chromatography were carried out. A decrease of 20% of the initial value at time 0 was used as the threshold for stability. The petrolatum preparations and the ethanolic solutions of budesonide and tixocortol pivalate were stable for at least the whole investigative period, irrespective of storage conditions, while Hc‐17‐B 1.0% in ethanol kept deep frozen was stable at least during the same period. The latter corticosteroid when kept at room temperature was stable for 3 months only.

A simple method for the detection of formaldehyde.

The commonly used chromotropic acid method for the determination of formaldehyde sometimes produces a masking discolouration. We have therefore evaluated a complementary method in which acetylacetone is used as the reagent. By a combination of the 2 methods, formaldehyde can be traced in most products.

Reliability of the chromotropic acid method for qualitative formaldehyde determination

Some questions. Probably there is contact sensitivity but is the dermatitis allergic eczematous; it looks more irritant, remains localized and does not vesiculate, thus lacking two of the cardinal signs of AECD. What is a correct patch test concentration? I find that more than 10 % is often irritant. What is the sensitizer? It seems to be water and ethanol soluble. Is it allyldisulphide which produces positive patch test reactions in some patients at 5 % pet.? Is it alliin or allicin or a breakdown product difficult to isolate? A major problem is patch testing in a suitable concentration with substances which are highly irritant and also labile. For practical management of such patients I do not patch test with garlic. A voidance of garlic is recommended but often does not seem to help this particular type of desiccated dermatitis. Nearly all of the culinary vegetables used by the homemaker have been reported to cause contact dermatitis in an industrial setting of large exposure (Mitchell & Rook 1978). Yet we rarely patch test for vegetable dermatitis in housewifes eczema. Significant screening and aimed test sets, appropriately standardized in nonirritant concentration and suitably preserved, are needed for vegetable AECD together with scratch/prick test sets for vegetable contact urticaria. The last has also been reported for Allium and is suspect in some of our cases.

Detection of formaldehyde in corticoid creams

In a previous report it was shown that the chromotropic acid method for determination of formaldehyde could give false negative results by discoloration (Dahlquist et a!. 1980). Therefore a fluorimetric method was used (Wilson 1974). This method had to be modified as we analyzed creams and not solutions. Formaldehyde was extracted from the specimens with 10 % methanol in water under magnetic stirring for 1 h. The extract was incubated with the reagent at 60° C for 1 h. The sample was filtered through a Millipor® teflon filter (0.22 f!m). (Some Millipor cellulose filters contained formaldehyde.) After measurement of the emission, the samples were examined by scanning from 400 to 700 nm to check that the maximum emission was at 510 nm. The detection limit was 5 f!g formaldehyde/g. Cosmetics, topical medicaments, dish washing liquids and shampoos giving discoloration with the chromotropic acid method were analyzed with the fluorimetric method. About half of the samples giving discoloration contained formaldehyde, confirming that the chromotropic acid method can give false negative results. Out of 20 corticoid creams, 16 gave positive reactions with the chromotropic acid method, but none gave discoloration. Analyzed with the fluorimetric method, these creams were found to contain up to 51 f!g formaldehyde/g. In seven corticoid ointments no formaldehyde amount above the detection limit was found. When the constituents of the creams were analyzed, formaldehyde was found in polyethylene glycols (carbowaxes, macrogol) and in derivatives of these. It is known that autoxidation of polyethylene glycols and derivatives gives formaldehyde among other compounds, and that heat increases the degradation (Rieger 1975, Hamburger et a!. 1975). Sterilization of corticoid creams and ointments is prescribed by Swedish law. The preparations are commonly heated at 140° C for 3 h. To investigate the formation of formaldehyde, polyethylene glycols and some derivatives were heated at 140° C for 3 h. Formaldehyde was determined by the qualitative chromotropic acid method. Several polyethylene glycols that had been stored in the laboratory contained formaldehyde. Only those free from formaldehyde were heated. Carbowax 400, 1500, 3000 and 4000 contained formaldehyde after heating. The derivatives Tween 60® (polyoxyethylene sorbitan monostearate) and Cetomacrogol (Texofor AlP, polyethylene glycol monocetylether) also formed formaldehyde during the heating procedure. When emulsions are made they are often heated at about 70° C. The Carbowax 3000 was heated at 70° C for 30 min and then contained formaldehyde. The amounts of formaldehyde found are probably not high enough to induce sensitization, but may maintain dermatitis in previously formaldehyde-sensitized subjects. The formaldehyde in the samples analyzed is, however, a contaminant, so the amount may vary between batches.

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 μg/cm2), formaldehyde (180 μg/cm2) and DU (200 μg/cm2). 74 consecutive patients and the 19 DU‐allergic patients were patch tested with a dilution series of DU (0 to 600 μg/cm2), formaldehyde (180 μg/cm) and IMID (200 μg/cm2). 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 μg/cm2 was found to be adequate and safe for both IMID and DU.