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The broad-spectrum herbicide glufosinate ammonium is a structural analogue of glutamate and acts in plants by inhibition of glutamine synthetase leading to a complete breakdown of ammonia metabolism. Owing to the structural analogy of glufosinate ammonium to glutamate, its effect on various glutamate-utilizing systems needed to be investigated in mammals. Although in laboratory animals glufosinate ammonium causes an inhibition of glutamine synthetase activity in different tissues, this inhibition led to slight increases of glutamate and ammonia levels at high sublethal and lethal doses only. After oral administration for 28 days, glufosinate ammonium had no effect on glutathione and carbohydrate metabolism and no effect on biosynthesis of non-essential amino acids in rats and dogs. Glufosinate ammonium does not interfere with various neurotransmitter receptors in vitro and does not influence the catecholamine neurotransmitter tissue concentrations after iv application. The results of these studies show that—in contrast to the plant metabolism—in mammals the inhibition of glutamine synthetase activity in various tissues does not lead to a breakdown of ammonia metabolism. The mammalian metabolism obviously compensates for this inhibition of glutamine synthetase activity by various other metabolic pathways. It is concluded that under the conditions of recommended use of glufosinate ammonium as an active ingredient in herbicides, a detrimental effect on the health of both users and consumers is extremely unlikely.

This paper reviews the results of toxicity studies conducted in laboratory animals to evaluate the safety of the herbicide trifluralin (TFL). The data show that TFL is slightly toxic following single oral exposure. Testing for embryotoxicity in rats and rabbits indicated no teratogenic potential, and many different mutagenicity tests showed that TFL was non-genotoxic. Subchronic and chronic toxicity testing in rats, mice and dogs indicated that TFL was haematotoxic (anaemia and methaemoglobinaemia), particularly in the dog, and slightly hepatotoxic. No-observed-effect levels of 4.8 and 41 mg/kg body weight/day, respectively, were determined in dogs and rats exposed chronically to TFL. Oncogenicity studies in rats and mice revealed no carcinogenic potential. Since the data for TFL indicated no mutagenic or other special toxicological risks, it is suggested that a safety factor of 100 could be used for the determination of the acceptable daily intake of TFL, which would be 0.05 mg/kg body weight/day.

The insecticide endosulfan was evaluated for chronic toxicity and carcinogenicity in long-term feeding studies in both Sprague-Dawley rats and NMRI mice. Dietary concentrations of the test substance were administered to rats at 0, 3, 7.5, 15 and 75 ppm and to mice at 0, 2, 6 and 18 ppm for 24 months each. In the rat study, only the treatment with the highest dose caused a significant reduction of body weight gains of the males and females at 75 ppm. The increased incidence of enlarged kidneys seen at autopsy at 75 ppm in females, and the slightly increased incidence of progressive glomerulonephrosis and slightly increased incidence of renal aneurysms seen histopathologically in the 75 ppm males, make the kidney the target organ in rats. On the basis of these findings a dietary concentration of 15 ppm is considered to be the no-observed-effect level (NOEL) in rats, equivalent to a daily test substance intake of 0.6 mg/kg body weight in males and 0.7 mg/kg body weight in females. In the mouse study, the treatment with 18 ppm caused a significant increase of mortality in the females and a slight (in the first third of the study, significant) reduction of body weight gain in males. Since there were no other substance-related findings, the dietary concentration of 6 ppm is considered to be the NOEL in mice, equivalent to a daily test substance intake of 0.84 mg/kg body weight in males and 0.97 mg/kg body weight in females. An evaluation of all relevant tumour data gained in both studies revealed no differences between control and treated groups. It was concluded, therefore, that endosulfan has no carcinogenic potential.

This article reviews the results of toxicity studies to evaluate the safety of the herbicide glufosinate ammonium (GLA) and its formulation (200 g/litre) in laboratory animals. The data show that GLA and its formulation are slightly toxic following oral exposure. In addition, the formulation induced GLA and its formulation are slightly toxic following oral exposure. In addition, the formulation induced slight dermal toxicity and eye irritation. Testing for teratogenicity in rats and rabbits indicated no teratogenic potential, and numerous mutagenicity tests showed GLA to be non-genotoxic. Chronic toxicity testing in rats and dogs yielded no-observable-effect levels of 2 and 5 mg/kg body weight/day, respectively. Oncogenicity studies in rats and mice revealed no carcinogenic potential. On the basis of these toxicity data it is concluded that this herbicide is safe under conditions of recommended use.

The paper presents a summary of different synthetic approaches to the Silaneophane Hoe 084498, which is a new Silicon based insecticide with promising efficiency in the protection of important crops, especially rice. In addition, some biological, ecological and toxicological data are given.

Mit histologischen und histochemischen Methoden lassen sich bei Xenopus-Larven 4 Zonen des interrenalen Gewebes (Nebennieren-Rinden-Gewebes) in caudo-cranialer Ausdehnung unterscheiden, die verschiedenen Phasen der Nebennierenentwicklung entsprechen. Diese Zonen wurden auf Grund der in ihnen am haufigsten auftretenden Zelldifferenzierungsformen als Blastemzone, Zone der Organbildung, Zone der Ausdifferenzierung und Zone der Funktionsphasen bezeichnet. Wahrend der Entwicklung verandert sich ihre Ausdehnung, sie verschieben sich von cranial nach caudal. Daneben kommt es wahrend der Ausdifferenzierung zu einer Verlagerung der Interrenalzellen von dorsal nach ventral. Die ausdifferenzierten Interrenalzellen durchlaufen einen Funktionszyklus. Charakteristische Differenzierungformen sind hierbei: wenig stimulierte, stark stimulierte, uberstimulierte Interrenalzellen sowie Zellen in der Restitutionsform und Degenerationsform. Kerngrosenmessungen und Bestimmungen der Steroiddehydrogenase-Aktivitat an Normaltieren zeigen eine Abhangigkeit der Nebennierenaktivitat von dem Entwicklungsstadium. Maxima der Aktivitat liegen im Stadium 59 und am Ende der Metamorphose vor. Untersuchungen des Organes nach Hypophysektomie und/oder ACTH-Behandlung machen den Einflus der Hypophyse auf die Normalentwicklung der Nebenniere deutlich. Hypophysektomie verhindert zwar nicht die Abgliederung der Nebenniereninseln vom Blastem, die Zellen differenzieren sich jedoch nicht vollstandig aus, sondern verharren in einer funktionellen Ruhepause. ACTH-Behandlung beschleunigt die Differenzierung und funktionelle Entwicklung der Interrenalzellen und fuhrt zu einer Vergroserung der einzelnen Interrenalkomplexe. Sie kompensiert auch die hemmende Wirkung der Hypophysektomie auf die Nebenniere. Auserdem vermag ACTH die durch Hypophysektomie bewirkte Wachstums-und Entwicklungshemmung teilweise auszugleichen.

The main uterine vessels of pregnant rats were clamped on day 14 for 30, 60, or 90 min. The fetal death rate was increased by 60 or 90 min clamping, proportional to duration. Some surviving fetuses showed skeletal retardation, bilateral limb anomalies, and cleft palate when examined on day 21. As early as 3 h after declamping, edema was seen in the mesenchymal tissue of the limbplates, together with a marked dilatation of the fetal vessels. Later this tissue became necrotic. The necrotic changes also involved surrounding mesenchyme including developing bone, which resulted in the observed limb malformations. In addition large blisters and hematomas at the tip of the snout may have caused tongue displacement to such an extent that palate closure was mechanically impaired. The malformations thus apparently resulted secondarily from necrosis of mesenchymal tissues that had been fully differentiated. This pathogenesis may be a common one for various malformations after impairment of fetal nutrition in rats at this particular develop mental stage.

The possibility of reducing the number of animals in sensitization studies (maximization method) is discussed on the basis of results from 20 sensitization tests. It appears that the number of test animals in sensitization studies may be reduced to ten treated animals and five control animals without prejudice to the quality of the test.