NTA and Fe(III)NTA: differential patterns of renal toxicity in subchronic studies.

Differential patterns in terms of nephropathology and 8-hydroxyguanine formation in the course of oral 28-day studies were observed with nitrilotriacetic acid (NTA) and FeNTA. FeNTA, but not NTA, caused enhanced 8-hydroxyguanine formation in kidney DNA after oral and intraperitoneal administration. Enhanced lipid peroxidation in the kidney homogenate was observed with FeNTA as well as with NTA. For NTA, the low dose (9 mg/kg per day) was without adverse effect. The kidney toxicity of oral FeNTA (50, 200, and 1000 mg/kg per day) was only mild, 50 mg/kg per day; however, it still led to an increased 8-hydroxyguanine content. The relevance of Iron(III) (Fe(III)) or Fe(III)NTA formation as a relevant mediator of NTA-related toxicity was excluded on the basis of these data. Also, a thermodynamic consideration presented here, supports the view that zinc (Zn), and not Fe, is likely to mediate the tubular cell cytotoxicity of NTA.

Cytokine expression profiles during murine contact allergy: T helper 2 cytokines are expressed irrespective of the type of contact allergen.

We have investigated the cytokine response pattern following sensitisation (induction) of BALB/c mice with different chemicals (dinitrochlorobenzene, dinitrofluorobenzene, oxazolone, glutaraldehyde, formaldehyde, trimellitic anhydride, croton oil) and elicitation (challenge) of contact allergy in sensitised animals. The results of our investigations showed that different chemicals induced both T helper (Th) 1 cytokines [interleukin (IL) 2, interferon beta (IFNgamma) [corrected] and Th2 cytokines (IL-4, IL-10) at different stages during murine contact allergy. We also confirmed our previous findings that IL-4 and IL-10 release were up-regulated during the challenge phase regardless the contact allergen used, whereas the release of IFNgamma [corrected] did not show a clear preference for being up- or down-regulated. In our hands, the increased expression of Th2 cytokines after challenge exposure to contact allergens appeared as a stable marker of secondary contact allergenic responses. Quantitative differences in the expression of IL-4 were observed between different contact allergens. The present results clearly indicate that skin sensitisers were able to elicit cytokine response patterns, which could not be related to a clear-cut Th1 or Th2 type of cytokine response. Furthermore, dermal application of contact allergens produced different kinetics of cytokine secretion upon induction and challenge. In our hands, the co-expression of Th1 and Th2 type cytokines appeared as a universal consequence of dermal application of contact allergens to responsive mice. Our results indicate that co-expression of Th1 and Th2 cytokines during contact allergy is an important feature of murine contact allergy in responsive mice and that chemicals differ in their potency to induce the expression of these cytokines. Furthermore, the results do not support the view that different chemicals induce Th1 or Th2 cytokines in a mutually exclusive manner depending on their preference for inducing either contact or respiratory allergy. The results are expected to renew the discussion about the usefulness of the Th1/Th2 paradigm in certain areas of immunotoxicology.

Studies on the design of animal tests for the corrosiveness of industrial chemicals.

Using a defined method for the determination of irritant and corrosive effects, the effects of varying the exposure time and the extent of occlusion were investigated and compared in rabbit skin experiments (by occlusive and semi-occlusive methods, each at exposure times of 1 hr and 4 hr). The results for 23 substances demonstrate that exposure for 1 hr normally leads to a realistic assessment of corrosiveness, in agreement with those given in the EEC 'Dangerous Substances Directive' (67/548/EEC; Off. J. Europ. Commun. 1967, 196, 1). With several substances, the 4-hr exposure leads to corrosive effects that do not occur under practical conditions. Moreover, a 4-hr exposure does not lead to a realistic hazard assessment in every case; some substances exhibit a corrosive effect in this test but are not classified as "corrosive" in the EEC Guideline Annex I, no. 1.1. Results using the semi-occlusive method did not usually differ from those obtained with the occlusive method. In general, the semi-occlusive method can be used, and in the case of volatile substances it is strongly advocated.

[Electron microscopic studies on the retina of the honey bee (Apis mellifica): II. Investigations on reactions of the fine structure of the rhabdomeric tubuli after exposure to various experimental influences, especially to light of different wavelength (author's transl)]. / Elektronenmikroskopische Untersuchungen am Auge der Honigbiene (Apis mellifica): II. Untersuchungen zu Reaktionen der Feinstrukturen des Rhabdoms auf verschiedene experimentelle Einflüsse, vor allem Reizlicht unterschiedlicher Wellenlänge

Electron microscopic studies were made on the fine structure of the rhabdomeric tubuli of the honey bee-eye after exposure to white and monochromatic light. Several preparation and fixation techniques were tested. A method to irradiate the eyes in vitro by high intensity of white or monochromatic light was developped.