Wolfgang Pittermann

Zeolithe A—A phosphate substitute for detergents: Toxicological investigation

Tests on Zeolithe A, a sodium aluminium silicate developed as a substitute for phosphates in detergents, were designed to investigate the safety of exposure to the material, or to detergents containing it, either under industrial conditions encountered during manufacturing processes or as a consequence of domestic use. The test programme included oral studies (acute, subchronic and long-term carcinogenicity tests and absorption measurements), and dermal, ocular and inhalation studies on the silicate alone and on appropriate detergent formulations, as well as studies of possible silicogenic activity and metal-complexing potential and measurements of dust generation and particle-size distribution. These studies did not produce any evidence to suggest that levels of domestic and industrial exposure resulting from the projected use of Zeolithe A in detergents would present any hazard to health. Zeolithe A did not induce silicotic tissue reactions and when incorporated into detergent formulations did not increase the liberation of fine dusts.

Efficacy testing of antimycotic prophylactics in an animal model.

Trichophyton mentagrophytes is both zoophilic and a common causative organism in human dermatomycosis. Therefore this dermatophyte is widely used for experimental efficacy testing of antimycotic agents and their active ingredients. The use of the guinea pig as an animal model for dermatomycosis is based on the predisposition of this species to spontaneous dermal fungal infections. A previously described guinea pig model was modified according to the results of pilot experiments. The modification consists of 1) evaluation of the infectious activity of the primary mycotic tissue cultures obtained from patients and 2) the efficacy testing itself with treatment of the infected skin area including the continuous clinical observation for 28 days. At first the required duration of cultivation and the number of spores for a reproducible infection of all animals were determined. The following efficacy test consisted of four groups with ten animals each. Group I (control of infection) remained without further treatment after experimental infections, groups II-IV received a single treatment by spraying at the day of infection with isopropanol (70%) (negative control), water (mechanic control) and the antimycotic agent (treated group), respectively. After 28 days under continuous examination, clinical symptoms (scabs; reddening, scaliness) were statistically analyzed. The model takes into account the duration and severity of infection in order to evaluate the differences between the four groups. The experimental protocol presented allows the efficacy of antimycotic agents to be demonstrated by means of statistical analyses. As an example the results of a successful prophylactic treatment against T. mentagrophytes with the antimycotic prophylactic Laudamonium (1%) are presented.

Assessment of the acute pulmonary toxicity of lamp oil aspiration in the isolated perfused rat lung

Mainly among children incidental ingestion of conventional lamp oils (paraffin oil) is responsible for casual intoxications with severe pulmonary toxicity and fatal consequences. On the basis of the isolated blood-free perfused rat lung we developed a model to study the acute toxic effects of lamp oil. Three oils were studied: conventional paraffin lamp oil (kinematic viscosity 1.62 10(-6) m(2)/sec), the methyl ester Edenor ME C12 70 (2.7 10(-6) m(2)/s) and another ester Edenor LPL (4.5 10(-6) m(2)/s). The oils were instilled into the trachea of isolated rat lungs and the changes in lung mechanics (tidal volume, pulmonary compliance and pulmonary conductance) as well as edema formation (increase in lung weight) studied. Instillation of as little as 10 microl paraffin oil caused complete failure of lung functions within 20 min and even 2 microl caused noticeable edema. Similar results were obtained with Edenor ME C12 70, which appeared to be even more toxic than paraffin oil, while Edenor LPL was less toxic. We conclude that tracheal instillation of oils into isolated perfused rat lungs may be a useful model to study the toxicity of lamp oils in vitro. Our findings further suggest that Edenor LPL may be a safer alternative for use as a lamp oil than paraffin oil.

Developmental toxicity of 2-ethylhexyl stearate.

2-Ethylhexyl stearate was investigated in an embryo-/foetotoxicity and teratogenicity study on rats according to OECD guidelines for the testing of chemicals (No. 414). Dose levels of 0 (arachidis oil), 100, 300 and 1000mg/kg body weight/day were administered by gavage. Dams tolerated the applied dose levels without any toxic effects. Pre- and post-implantation loss and mean numbers of resorptions were unaffected by treatment. All parameters were comparable with the animals of the control group. Skeletal and visceral investigations revealed no treatment-related malformations. For embryo-/foetotoxicity, teratogenicity and maternal toxicity a NOAEL of 1000mg/kg was deduced.