Dynamics of the interfacial film in bicontinuous microemulsions based on a partly ionic surfactant mixture: A neutron spin-echo study.

In a microemulsion system based on a mixture of nonionic and ionic surfactants the addition of alcohol instead of changing the temperature was used to tune the curvature of the surfactant interface. The influence of the addition of the short-chain alcohol 2-propanol in the system water-perchloroethylene- Marlowet IHF-2-propanol is studied using neutron spin-echo spectroscopy. In contrast to alcohols with long alkyl chains 2-propanol is no strong co-surfactant, but changes the properties of the solvents. The present contribution focuses on the bicontinuous phase in this system and a quantitative analysis of the obtained neutron spin-echo data is proposed within the theoretical framework given by Zilman and Granek for amphiphilic membranes. It turns out that, in addition to the local movements of the surfactant film, also a collective diffusional mode of the bicontinuous structure has to be taken into account. The presented approach allows to calculate the bending elastic constant κ of the film. The approach is subsequently applied to follow changes of κ as induced by changes of the alcohol concentration.

Distribution and excretion of orally administered oleic acid anilide in the rat.

Oleic acid anilide [aniline-14C(U)] was administered by gastric tube to male rats in a single dose (10 mg/kg body weight). After intervals of 3, 6, 24 or 120 h the excretion of radioactivity and the distribution in different organs were studied. The radioactivity was eliminated rapidly through the urine and faeces containing 62% and 38%, respectively, after 24 h. At this time the excretion was almost complete. No radioactivity could be found in the expired air. The absorbed oleic anilide was easily deacylated as evidenced by the excretion of N-acetyl-p-aminophenol conjugate as the main urinary metabolite representing 60-70% of the urinary radioactivity. The radioactivity in faeces was due to the unchanged substance. Twenty-four hours after administration only 0.7% of the dose remained in the total organism with the highest concentrations in the red blood cells, spleen and forestomach. Even after 5 daily doses, an accumulation of radioactivity could not be found.

Effect of ethanol on the induction of lung tumours by ethyl carbamate in mice.

Groups of 25 female NMRI-mice received daily doses of 0, 18, 36, 90, or 180 mg ethyl carbamate/kg body wt either in water or in 20% ethanol by gavage for 8 weeks. Another 8 weeks later, the animals were sacrificed and lung adenomas were counted. Ethyl carbamate was found to increase the number of lung adenomas per mouse dose-dependently in all dose groups. No significant differences, however, were observed between groups receiving ethyl carbamate in water or in 20% ethanol. Thus, ethanol had no effect on ethyl carbamate induced tumourigenesis.

Effects of BHA and related phenols on the forestomach of rats.

To determine the pathogenesis of BHA-induced forestomach lesions, the nature and time course of the early lesions in the forestomach of Wistar rats were studied. The rats were given BHA at a dose level of 2% in a powdered diet or by oral intubation of 1 g BHA/kg body weight/day in arachis oil. The hyperplastic changes in the mucosa were visible 1 day after the second application. The localization was dependent on the mode of application. Dietary exposure yielded changes in the area of the limiting ridge; oral intubation of BHA produced lesions in the apex of the forestomach. In a subchronic 90-day feeding study in rats, no recognizable effect was observed when 0.125% BHA was incorporated into the diet as a solution in arachis oil. In reversibility studies, severe forestomach lesions observed after feeding 2% BHA for 6, 12 or 15 months regressed almost completely following withdrawal of the BHA for a period of 7 months. BHA induced similar forestomach damage in NMRI mice and Syrian golden hamsters, whereas guinea-pigs, a species having no forestomach, did not show comparable lesions. Substances with similar chemical structure were tested in short-term feeding studies (tert-butylhydroquinone, 4-methoxyphenol, 1,4-dimethoxybenzene, hydroquinone, 3-methoxyphenol, 2-methoxyphenol, anisole, p-cresol, phenol and BHT). Only 4-methoxyphenol strongly affected the forestomach mucosa in a manner similar to that associated with BHA. The methoxy group in the para position seems to be important for the hyperplasiogenic activity.

Induction of early lesions in the forestomach of rats by 3-tert-butyl-4-hydroxyanisole (BHA).

BHA was administered to Wistar rats at a dose level of 2% in a powdered diet for periods of 1, 2 and 4 wk. After 1 wk epithelial damage, mild hyperplasia and hyperkeratosis of the forestomach mucosa was observed. The hyperplasia and hyperkeratosis showed progression at wk 2 and 4 whereas other epithelial defects regressed. The lesions were most pronounced in the vicinity of the limiting ridge. A further 4 wk of feeding without BHA resulted in a complete regression of epithelial defects, although the hyperplastic changes were still apparent. Other rats were given 1 g BHA/kg body weight/day by gastric intubation in arachis oil for 1, 2, 4, 8, 16 or 32 days. Increased mitotic activity was observed after 1 day and mild hyperplasia after the second intubation, but inflammatory response and superficial defects were not prominent and the hyperplasia of the squamous epithelium did not appear to result from initial damage and subsequent hyper-regenerative activity. A gradual regression of the hyperplastic changes occurred after eight daily intubations. The lesions were found in the apex of the forestomach remote from the limiting ridge. It is concluded that BHA incorporated in powdered diet or given in arachis oil by oral intubation causes lesions in the rat forestomach similar to that reported for BHA given in a pelleted diet (Ito et al. J. natn. Cancer Inst. 1983, 70, 343; idem, Gann 1983, 74, 459). The hyperplastic changes in the mucosa occur rapidly and their localization is dependent on the mode of application. Following withdrawal of the BHA there was almost complete regression of the lesion, only a residual mild hyperplasia remaining after 4 wk.

Structure of biodiesel based bicontinuous microemulsions for environmentally compatible decontamination: A small angle neutron scattering and freeze fracture electron microscopy study.

Most toxic industrial chemicals and chemical warfare agents are hydrophobic and can only be solubilized in organic solvents. However, most reagents employed for the degradation of these toxic compounds can only be dissolved in water. Hence, microemulsions are auspicious media for the decontamination of a variety of chemical warfare agents and pesticides. They allow for the solubilization of both the lipophilic toxics and the hydrophilic reagent. Alkyl oligoglucosides and plant derived solvents like rapeseed methyl ester enable the formulation of environmentally compatible bicontinuous microemulsions. In the present article the phase behavior of such a microemulsion is studied and the bicontinuous phase is identified. Small angle neutron scattering (SANS) and freeze fracture electron microscopy (FFEM) measurements are used to characterize the structure of the bicontinuous phase and allow for an estimation of the total internal interface. Moreover, also the influence of the co-surfactant (1-pentanol) on the structural parameters of the bicontinuous phase is studied with SANS.

Toxicokinetics of chloroethanol in the rat after single oral administration.

The excretion and tissue distribution of 14C-labelled chloroethanol were studied in rats following single oral administration of 5 and 50 mg/kg body weight. At both dose levels, the radioactivity was rapidly eliminated, mainly in the urine. On the first day after application of 5 mg/kg body weight, 77.2% of the dose were found in the urine, 1.7% in the faeces, and 1.0% as carbon dioxide in the expired air. Only 2.8% were excreted by these routes during the following 3 days. The residual radioactivity remaining in the tissues after 4 days was almost equally distributed and amounted to about 0.4% of the dose in the liver and 3% in the whole organism. At the higher dose level, excretion rates and tissue concentrations were similar. Examination of the urine by anion exchange chromatography on DEAE-Sephadex revealed two metabolites which were identified by GC/MS analysis as thiodiacetic acid and thionyldiacetic acid. These metabolites represented almost the whole urinary radioactivity. They were excreted in approximately equal amounts at the low dose whereas the thiodiacetic acid predominated with about 70% of the urinary radioactivity at the high dose. Unchanged chloroethanol, chloroacetic acid, S-carboxymethylcysteine and sulphonyldiacetic acid were not found in the urine.

[Metabolism of 3-amino-1,2,4-triazole in rats]. / Uber den Stoffwechsel von 3-Amino-1,2,4-triazol in Ratten

3-Amino-1,2,4-triazole[5-(14)C] was administered orally to rats as a single dose of 50 mg/kg body weight. Excretion in urine and feces was followed during a period of 3 days. Within the first 24 hrs the main part of the radioactivity was found in the urine as unchanged amitrole. 3-Amino-5-mercapto-1,2,4-triazole and 3-amino-1,2,4-triazolyl-(5)-mercapturic acid were isolated from urine and identified by comparison with synthetic compounds. The total amount of these metabolites in the urine was about 6% of the dose. The metabolic pathways of amitrole and the possible relations between biotransformation and toxicity are discussed.

Coumarin mercapturic acid isolated from rat urine indicates metabolic formation of coumarin 3,4-epoxide.

A coumarin mercapturic acid, N-acetyl-S-(3-coumarinyl)cysteine, has been identified in the urine of coumarin-treated rats. [14C]Coumarin was applied by gavage as a single dose to male Wistar rats (10-150 mg/kg body weight). Twenty-four-hour urine was collected, and the deproteinized concentrate was analyzed for radiolabeled metabolites by HPLC. The new mercapturic acid metabolite is supposed to result from oxidative biotransformation of coumarin to its 3,4-epoxide and subsequent coupling with glutathione.

Induction of forestomach lesions by butylhydroxyanisole and structurally related substances.

Butylated hydroxyanisole (BHA) is widely used as an antioxidant in foodstuffs, in materials which come into contact with food and also in cosmetic products. The safety of BHA was questioned, however, when it was reported that in a recent Japanese carcinogenicity study 2% BHA in a pelleted diet caused hyperplasia, papillomas and squamous cell carcinomas in the forestomach of rats. In order to clarify whether substances with a similar chemical structure would also induce forestomach lesions, BHA was compared with some related chemicals in 28 day feeding studies. For this purpose groups of 5 to 10 Wistar rats were fed diets containing 2% BHA, 2% tert.-butylhydroquinone (TBHQ), 2% 4-methoxyphenol, 2% 1,4-dimethoxybenzene, 2% hydroquinone or 1% butylated hydroxytoluene (BHT), respectively, for periods of 4 weeks. BHA treatment caused severe diffuse hyperplasia, acanthosis and hyperkeratosis in the forestomach mucosa which was most pronounced in the vicinity of the limiting ridge. In TBHQ treated animals brownish discolorations of the mucosa and mild hyperplasia with focally increased hyperplasia of basal cells were observed. In the case of p-hydroxyanisole a circular deep ulceration parallel to the limiting ridge occurred with hyperplasia and mild hyperkeratosis in the adjoining mucosa. Hydroquinone caused only mild hyperplastic and hyperkeratotic areas near the oesophageal entry in a few cases. The feeding of BHT induced no visible forestomach lesions. The strong effects of BHA and 4-methoxyphenol and the more or less inactivity of BHT and hydroquinone indicate that the methoxy group of the tested anisoles might be involved in their hyperplasiogenic activity.