Evaluation de la toxicité aiguë des produits de combustion des fumigènes

En 1993 la société LACROIX, dans le cadre d'une meilleure connaissance de ses produits, a voulu tester la toxicité des produits de combustion des fumigènes dans des conditions d'utilisation normales ou accidentelles. Pour répondre à cette question, nous avons interrogé les bases de données toxicologiques et la bibliographie. Nous n'avons trouvé qu'un petit nombre d'articles pertinents (1, 2, 3), mais si ces documents nous permettent d'obtenir quelques informations, aucun ne répond spécifiquement à la question de la toxicité du fumigène dans nos conditions d'utilisation. C'est la raison pour laquelle nous avons pris contact avec l'INERIS afin de définir les besoins nécessaires à l'évaluation des risques concernant l'utilisation de notre fumigène. L'évaluation des risques d'un fumigène implique une caractérisation des produits de combustion, une évaluation expérimentale de la toxicité provenant de ces produits administrés par voies d'inhalation chez l'animal et enfin l'évaluation des conditions d'exposition aux produits de combustion en cas d'exposition réelle, accidentelle ou non. En fonction de ces besoins nous avons défini un certain nombre d'essais qui vous sont présentés dans la suite du document

An evaluation of the carcinogenic potential of five man-made vitreous fibers using the intraperitoneal test

International audienceThe objective of this study was to evaluate the potential carcinogenic hazard of five man-made vitreous fibers (MMVF) following the recommendations of the dust subgroup of the German Maximale Arbeitsplatz Konzentration (MAK) Commission. This was done by rating the tumors arising from intraperitoneal injection in the rat, relative to the number of injected fibers with length (L) > 5 mu m, diameter (Di 5 contained in the sample. Fibers from glass and stone wools were selected for this evaluation. At the outset of this study, because of their chemical composition, the substances tested were considered new-generation insulation wool fibers. As an example, their "solubility" as measured in vitro at pH 7.4 was higher than those of insulation wool fibers used at that time. The samples have been specially manufactured and processed in order to improve their concentration in fibers fitting the criteria of length and diameter required by the protocol of this study. This was done for several purposes. The first one was to test fibers that are as similar as possible to those encountered at the workplace (median diameter below I mu m and median length between 10 and 15 mu m), in order to facilitate extrapolation to the human situation. The second one was to allow injection of the highest possible dose of fibers under a tolerable volume, since too large a volume and/or too high a number of injections may increase the risk of artifactual responses. In addition, the highest doses were selected on the basis of the recommendations of the dust subgroup of the German MAK Commission along with our decision to limit the number of injections to two. Female Wistar rats were used as a model. They received an intraperitoneal injection of various masses (from 0.7 to 55 mg) of sample, and then were followed during an observation period of 130 wk. The positive controls (long-fiber crocidolite from 0.005 to 0.5 mg) exhibited a significant dose-related occurrence of mesotheliomas. According to the MAK Commission criteria, a carcinogenic potential was demonstrated for fiber H (at the highest dose, 55 mg). The other fibers (A, C, F, and C) did not show any statistically significant carcinogenic potential at the tested doses

Effects of low level ozone exposure on rat pulmonary inflammatory response

International audienc

Opinion on Not Terminating Control Animals in the Recovery Phase of Non-rodent Toxicology Studies

Nonclinical toxicology studies required to support human clinical trials of new drug candidates are generally conducted in a rodent and a non-rodent species. These studies typically contain a vehicle control group and low, intermediate, and high dose test article treatment groups. In addition, a dosing-free recovery phase is sometimes included in toxicity studies to demonstrate reversibility of toxicities observed during the dosing phase and may include additional animals in the vehicle control and one or more dose groups. Typically, reversibility is determined by comparing the test article-related changes in the dosing phase animals to concurrent recovery phase animals at the same dose level. Therefore, for interpretation of reversibility, it is not always essential to terminate the recovery vehicle control animals. In the absence of recovery vehicle control tissues, the pathologist’s experience, historical control database, digital or glass slide repositories, or literature can be used to interpret the findings in the context of background pathology of the species/strain/age. Therefore, in most studies, the default approach could be not to terminate recovery vehicle control animals. This manuscript provides opinions on scenarios that may or may not necessitate termination of recovery phase vehicle control animals in nonclinical toxicology studies involving dogs and nonhuman primates

Nonproliferative and proliferative lesions of the rat and mouse endocrine system

© 2018 The Japanese Society of Toxicologic Pathology. The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) Project (www. toxpath.org/inhand.asp) is a joint initiative among the Societies of Toxicological Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP) and North America (STP) to develop an internationally accepted nomenclature for proliferative and nonproliferative lesions in laboratory animals. The purpose of this publication is to provide a standardized nomenclature for classifying microscopic lesions observed in the endocrine organs (pituitary gland, pineal gland, thyroid gland, parathyroid glands, adrenal glands and pancreatic islets) of laboratory rats and mice, with color photomicrographs illustrating examples of the lesions. The standardized nomenclature presented in this document is also available electronically on the internet (http://www.goreni.org/). Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes spontaneous and aging lesions as well as lesions induced by exposure to test materials. A widely accepted and utilized international harmonization of nomenclature for endocrine lesions in laboratory animals will decrease confusion among regulatory and scientific research organizations in different countries and provide a common language to increase and enrich international exchanges of information among toxicologists and pathologists