Toxicological European research. Recherche europeenne en toxicologie最新文献

Chemical substances as feed additives, pesticides, drugs or natural toxicants, may enter in the body of farm animals. They are then accumulated, transformed in metabolites more toxic but, generally, less toxic than initial ingested compounds. Farm animals are a biologic active relay able to change entirely conclusions from a direct toxicological evaluation on laboratory animals. It must be also underlined that physical and chemical very sophisticated methods carried out for isolation of toxics are not always in agreement with "in vivo" assays. We must consider residues availability. The methodology called "relay toxicity" consists essentially on the submission of the animal product which contain a mosaic of residues available or not, to long term testing in laboratory animal as pseudo-consumers. So it is possible to measure influences of a lot of metabolite in a dietary context. For these reasons we are thinking it is an appropriate procedure, taking its place among the test to be undertaken for a biological and a more realistic evaluation of additives drugs, pesticides residues or natural toxicants in the feeds of farm reared animals whose meat, eggs or milk will be eaten by human consumers.

Due to the use of radiolabeled drugs and feed additives in residue evaluation of preclearance approval of new animal drug applications (NADAs), metabolites including those which are covalently bound are detected in the edible tissues of target food animals. Isolation and characterization of these residues is often a difficult task. The approach taken is to couple safety assessment with development of the required residue information. An outline of data development is made in the context of toxicity assessment. Unless otherwise adjusted, the sponsor's method of residue analysis and drug withdrawal time reflect responsibility of all drug residues of toxicological concern found in edible tissues. The use of bioavailability studies and how they interact with safety evaluation is developed. Focus is brought to the specific problem of covalently bound residues and a framework for their assessment is presented.

4 cases of subcutaneous injection of metallic mercury are reported and compared with those recorded by others. Subcutaneous injection always causes local inflammatory reaction and granuloma formation. Systematic mercury absorption is the rule as it is proved by high mercury levels in blood and urine. Nevertheless this absorption is usually too small to be responsible for toxic manifestations. Surgical excision of all accessible contaminated subcutaneous areas should be performed. When residual mercury is roentgenographically detectable regular monitoring of CNS, renal function and urinary and/or blood mercury levels are necessary.

Considering the diversity of previous observations given by literature about the metabolic fate or arsenic, the authors using a radioactive tracer, study the pharmacokinetics of that arsenical derivative after giving the mouse a non toxic dose. By the oral route, this compound is quickly absorbed and resorbed. The elimination process mainly occurs by renal route then by the faecal route. The blood results or the concentrations in the tissues do not reveal any retention process though the latter always rise above blood levels. During the first two hours the concentrations in the thymus seem to be particularly interesting.

Strains of E. coli and Str. faecalis, which do not darken in the presence of Bismuth in vitro, and which had been previously isolated from faeces of patients having presented bismuthic myoclonic encephalopathy, were implanted in the digestive tract of axenic rats. Then these monoxenic rats were treated orally for 15 days with bismuth subnitrate (0,24 millimoles = 50 mg/animal/day) and sacrificed on day 16. At this time, levels of bismuth in blood, brain, kidney and femur from these rats did not significantly differ from those obtained from axenic rats or monoxenic rats implanted with the homologous bacterial strains which darken in the presence of bismuth. Conversely, under the same conditions, levels of bismuth in kidney, muscle and femur were significantly lower in holoxenic rats than in axenic rats. Levels of bismuth in kidney and femur were also significantly lower in holoxenic rats than in monoxenic rats implanted with one of the four bacterial strains mentioned above.