Contact allergy induced by bisphenol A diglycidyl ether leachables from aluminium tubes for pharmaceutical use.

BACKGROUND: Aluminium tubes for pharmaceutical use are internally lacquered with epoxy resins (ER) based on bisphenol A diglycidyl ether (BADGE). Recently, it was shown that remnants of ER polymerization like BADGE are extractable from epoxy-based coatings of commercially available tubes and may leach into semi-solid drug preparations. We aimed to evaluate the safety of BADGE-contaminated macrogol ointments in individuals sensitized to ER based on BADGE by use tests. METHODS: Repeated open application testing (ROAT) in 11 patients sensitized to ER based on BADGE with BADGE in macrogol ointments (3 mg/kg; 30 mg/kg, equivalent to BADGE concentration determined in macrogol ointment after storage in a commercially available tube; 300 mg/kg). RESULTS: The 30 mg/kg BADGE ointment elicited reactions in three patients, and another three patients reacted to 300 mg/kg BADGE ointment. No reactions to the vehicle control and 3 mg/kg BADGE were observed. CONCLUSIONS: Elevated BADGE concentrations in ER-coated aluminium tubes pose a risk of developing contact dermatitis to patients sensitized to ER based on BADGE. Quality standards are deemed necessary for the production of ER-coated aluminium tubes intended for pharmaceutical use and should consider the results of the present ROAT study.

[Rehabilitation for occupational dermatoses. Outpatient and inpatient measures]. / Rehabilitation bei Berufsdermatosen. Ambulante und stationäre Massnahmen.

In recent years, the number of reports of suspicions of occupational diseases, received by the public statutory employer's liability insurance bodies, has remained constant. The recognition of occupational diseases under number 5101 BKV, however, has decreased considerably. This is more than likely due to improved prevention management concepts by the public statutory employer's liability insurance bodies. Nevertheless there are still severe occupational skin diseases that are resistant to or relapse under therapy, thus threatening discontinuation of the occupation. For these cases, an interdisciplinary inpatient treatment as a tertiary individual prevention measure was introduced. This consists of a three-week inpatient period followed by a three-week outpatient sick leave for further stabilization of the skin condition. During the inpatient stay intensive dermatological diagnosis and treatment are accompanied by in-depth health education seminars and psychological interventions. The selection of individually suitable skin protection measures and their practical trial in a workplace simulation model with an ergotherapist are of particular importance. Evaluations of this program showed that two-thirds of the participants with the defined risk of having to give up their occupation were able to continue with their occupation on a long-term basis.

[Effect of cadmium, zinc, lead and mercury on enzyme activity in Saccharomyces cerevisiae]. / Der Einfluss von Cadmium, Zink, Blei und Quecksilber auf die Enzymaktivität bei Saccharomyces cerevisiae in vivo.

The in vivo influence of cadmium, zinc, lead, and mercury on the activities of intracellular enzymes in Saccharomyces cerevisiae has been studied. Cadmium and lead cause a significant increase of the enzyme activities. Zinc and mercury do not affect the enzyme activities but they intensify considerably the effects of cadmium and lead. A reduction of enzyme activities is found only rarely. Interactions between the heavy metals tested can lead to synergism or to antagonism or rather to an addition of the effects. The findings suggest that under in vivo conditions heavy metals show only an indirect influence on intracellular enzymes.

[Effect of cadmium, zinc, lead and mercury on the enzyme activity in Saccharomyces cerevisiae in vitro]. / Der Einfluss von Cadmium, Zink, Blei und Quecksilber auf die Enzymaktivität bei Saccharomyces cerevisiae in vitro.

The difference between cadmium, zinc, lead, and mercury in regard of their effects on the activity of the enzymes tested is very slight. Concentrations higher than 10(-5) M reduce significantly the activity of the enzymes, and concentrations of approximately 10(-3) M inhibit it completely. An increase of the activity cannot be detected. The addition of combinations of cadmium, zinc, and lead results in a summing up of the toxic effects, whereas the interaction between mercury and the other three heavy metals shows a cumulative effect, which is appointed nearly completely by the heavy metal more toxic. The findings suggest that under in-vitro conditions there exists a direct interaction between the heavy metals and the enzymes.

[Effect of heavy metal interactions on the growth of Saccharomyces cerevisiae]. / Einfluss von Schwermetallinteraktionen auf das Wachstum von Saccharomyces cerevisiae.

The influence of interactions of cadmium, zinc, lead, and mercury on the growth of Saccharomyces cerevisiae has been studied. Generally the experiments resulted in the following findings: Low zinc concentrations reduce the toxicity of cadmium while high zinc concentrations intensify the effects of cadmium. Zinc does not decrease the growth inhibition by mercury. The actions of cadmium and mercury are not changed by lead, but 5 X 10(-4) M lead prevent completely the increase of the growth intensity caused by zinc. Combinations of toxic concentrations of cadmium and mercury show a synergistic lengthening of the lag period, but their cumulative influence on the growth rate is lower than the sum of the corresponding inhibition effects.

[Effects of cadmium, zinc, lead and mercury on the growth and accumulating ability of Saccharomyces cerevisiae, Saccharomycopsis lipolytica, Candida tropicalis, and Candida utilis]. / Der Einfluss von Cadmium, Zink, Blei und Quecksilber auf das Wachstum und das Akkumulationsvermögen von Saccharomyces cerevisiae, Saccharomycopsis lipolytica, Candida tropicalis und Candida utilis.

The effects of cadmium, zinc, lead, and mercury on the growth and the accumulating ability of Saccharomyces cerevisiae, Saccharomycopsis lipolytica, Candida tropicalis, and Candida utilis had been studied. Generally the experiments resulted in the following findings: Very small concentrations of cadmium and mercury already decrease the growth intensity of the yeasts by lengthening the lag period and the doubling time. The cell yield is not reduced. Zinc increases the productivity of Saccharomyces cerevisiae and Saccharomycopsis lipolytica by shortening the lag period. The lead concentrations investigated show no significant influence on the growth. Low pH values intensify the effectiveness of the four heavy metals. The yeasts tested accumulate heavy metals, especially cadmium, to high concentrations and therefore substrates containing heavy metals are only limited suitable for the scp-production with yeasts.

[Evaluation of the effectiveness of high voltage irradiation of malignant gynecologic tumors in a nude mouse model]. / Effektivitätsbeurteilung der Hochvoltbestrahlung bei malignen gynäkologischen Tumoren am Modell der Nacktmaus.

Not only the effect of cytostatic drugs and hormones, but also that of ionizing radiation can be tested after transplantation of human tumoral tissue into nu/nu mice with thymic aplasia. In this study, the effects of high voltage irradiations dosed up to 60 Gy (fractionation 2 X 5 Gy per week) to three carcinomas of the endometrium, three carcinomas of the cervix, three ovarian carcinomas, and one mammary metastasis of an immunoblastic sarcoma were observed during a period of 120 days. This irradiation plan could be performed without problems in eight cases, in two cases it had to be stopped after 50 Gy. Nine tumors decreased significantly in size, reaching sizes which were below those measured before irradiation. In six among the nine cases, the tumors grew again after different periods of observation. In case of rather long periods of observation, those points within the curves of development can be taken as efficacy indices which are representing the lowest or the initial values of tumor sizes. In another study, the effects of high voltage irradiation to tumors of the nude mouse are correlated to those found in the corresponding patients.