Istraživanja o otrovanju kadmijem

Nous avons élaboré une méthode pour la microdéterminaton néphêlémetrique du cadmium. Cette méthode fut utilisée dans l\u27étude de la distribution et de l\u27excrétion du cadmium au cours des intoxications. L\u27étude de l\u27élimination du cadmium au cours d\u27intoxications expérimentales a montré que le cadmium est un poison cumulatif.1. lzradili smo metodu za nefelometrijsko mikroodređivanje kadmija. Metoda se osniva na taloženju kadmija u obliku brucin-jodo-kadmijata pod pH 5. Utvrdili smo uvjete za primjenu te metode na biološki materijal: mineralizacija sa sumpornom, dušičnom i perklornom kiselinom, koprecipilacija s bakarnim sulfidom i uklanjanje bakra pomoću kupferona kod pH 3-3,5. 2. Tu smo metodu primijenili pri proučavanju raspodjele i izlučivanja kadmija u toku otrovanja: a) Kakav god bio način otrovanja i vrsta eksperimentalne životinje, pod našim eksperimentalnim uvjetima (supkutana injekcija) kadmij se fiksira selektivno u nekim organima, i to u jetri i u bubrezima. U nekim oblicima supkutanog ili kroničnog otrovanja slezena i neke endokrine žlijezde (naročito nadbubrežna žlijezda) također zadržavaju znatne količine metala. Metal se nalazi također i u dlakama; to smo utvrdili i kod ljudi, koji su profesionalno eksponirani kadmiju. S tim u vezi dali smo i neke podatke o otrovanju kadmijem u francuskim tvornicama »alkalnih« akumulatora. U krvi je kadmij naročito lokaliziran u krvnim tjelešcima. Protivno od Friberga uvijek smo našli male količine kadmija u plazmi (odnos kadmija u krvnim stanicama i plazmi: 17,5 do 19,7). Medu organima, koji zadržavaju razmjerno malo kadmija, treba istaknuti mozak, srce i pluća, i, bar u slučaju kroničnih otrovanja, koštano tkivo. Raspravlja se o odnosu lokalizacije u različitim organima i simptoma profesionalnog i eksperimentalnog otrovanja. Tom su prilikom ukratko naznačeni neki originalni rezultati histoloških i biokemijskih. istraživanja. b) Istraživanje eliminacije kadmija u toku eksperimentalnih otrovanja pokazalo je, da je kadmij kumulativni otrov. Za medicinu rada od velikog je značenja dugo zadržavanje kadmija u organizmu; po tom je kadmij vrlo sličan drugim teškim metalima, a naročito živi, olovu i taliju. Na taj se način može objasniti toksično djelovanje utvrđeno kod radnika, koji su dugo vremena bili eksponirani vrlo malim količinama kadmija. Obzirom na prevenciju ti nalazi ističu važnost čestih pregleda atmosfere u radionicama, u kojima bi se mogao naći kadmij, i potrebu izrađivanja ultra-osjetljivih metoda za određivanje kadmija

Read-Across of 90-day Rat Oral Repeated-Dose Toxicity: A Case Study for Selected n-Alkanols

n-Alkanols provide an excellent example where a category-approach to read-across may be used to estimate the repeated-dose endpoint for a number of untested derivatives (target chemicals) using experimental data for tested derivatives (source chemicals). n-Alkanols are non-reactive and exhibit the unspecific, reversible simple anaesthesia or non-polar narcosis mode of toxic action in that the metabolic products of the parent alcohols do not contribute to the toxic endpoint evaluated. In this case study, the chemical category is limited to the readily bioavailable (C5 to C13) analogues. The toxicokinetic premise includes rapid absorption via the gastrointestinal tract, distribution in the circulatory system, and first-pass metabolism in the liver resulting in metabolism via oxidation to CO2 and with minor elimination of oxidative intermediate as glucuronides. Two analogues have experimental 90-day oral repeated-dose toxicity data which exhibit qualitative and quantitative consistency. Typical findings include decreased body weight, slightly increased liver weight which, in some cases, is accompanied by clinical chemical and haematological changes but generally without concurrent histopathological effects at the Lowest Observed Effect Level (LOEL). Chemical similarity between the analogues is readily defined by a variety of structure-related properties; data uncertainty associated with toxicokinetic and toxicodynamic similarities is low. Uncertainty associated with mechanistic relevance and completeness of the read-across is reduced by the concordance of in vivo and in vitro results, as well as high throughput and in silico methods data. As shown in detail, the 90-day oral repeated-dose toxicity No Observed Effect Level (NOEL) value of 1000 mg/kg bw/d for 1-pentanol and 1-hexanol based on LOEL of very low systemic toxicity can be read across to fill the data gaps of the untested analogues in this category with acceptable uncertainty

EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF); Scientific Opinion on Flavouring Group Evaluation 9, Revision 4 (FGE.09Rev4): Secondary alicyclic saturated and unsaturated alcohols, ketones and esters containing secondary alicyclic alcohols from chemical group 8 and 30, and an ester of a phenol derivative from chemical group 25

<p>The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to evaluate 21 flavouring substances in the Flavouring Group Evaluation 9, Revision 4, using the Procedure in Commission Regulation (EC) No 1565/2000. The present revision of FGE.09 includes the assessment of four additional flavouring substances, p-menthan-3-one [FL-no: 07.059], 2,6,6-trimethylcyclohex-2-en-1-one [FL-no: 07.202], l-piperitone [FL-no: 07.255] and menthol 1-and 2-propylene glycol carbonate [FL-no: 09.843]. None of the substances were considered to have genotoxic potential. The substances were evaluated through a stepwise approach (the Procedure) that integrates information on structure-activity relationships, intake from current uses, toxicological threshold of concern, and available data on metabolism and toxicity. The Panel concluded that the 20 substances [FL-no: 02.070, 02.075, 02.135, 02.167, 06.136, 07.059, 07.202, 07.203, 07.255, 09.154, 09.355, 09.520, 09.618, 09.619, 09.621, 09.843, 09.870, 09.929, 09.935 and 09.949] do not give rise to safety concerns at their levels of dietary intake, estimated on the basis of the MSDI approach. For the remaining candidate substance [FL-no: 07.207], additional toxicity data are requested (further metabolism and/or toxicity studies). Besides the safety assessment of these flavouring substances, the specifications for the materials of commerce have been considered. Specifications including complete purity criteria and identity for the materials of commerce have been provided for all candidate substances.</p&gt

EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF); Scientific Opinion on Flavouring Group Evaluation 12, Revision 2 (FGE.12Rev2): Primary saturated or unsaturated alicyclic alcohol, aldehyde, acid, and esters from chemical group 7

The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to evaluate 10 flavouring substances in the Flavouring Group Evaluation 12 (FGE.12), including an additional substance in revision 3, using the Procedure in Commission Regulation (EC) No 1565/2000. This revision is made due to inclusion of one additional flavouring substance, 2,6,6-trimethylcyclohex-2-ene-1-carboxaldehyde [FL-no: 05.182]. None of the substances were considered to have genotoxic potential. The substances were evaluated through a stepwise approach (the Procedure) that integrates information on structure-activity relationships, intake from current uses, toxicological threshold of concern, and available data on metabolism and toxicity. The Panel concluded that all 10 substances [FL-no: 02.134, 02.186, 05.157, 05.182, 05.183, 05.198, 08.135, 09.342, 09.670 and 09.829] do not give rise to safety concerns at their levels of dietary intake, estimated on the basis of the MSDI approach. Besides the safety assessment of these flavouring substances, the specifications for the materials of commerce have also been considered. Specifications including complete purity criteria and identity for the materials of commerce have been provided for all 10 candidate substances

Dispelling urban myths about default uncertainty factors in chemical risk assessment - Sufficient protection against mixture effects?

© 2013 Martin et al.; licensee BioMed Central LtdThis article has been made available through the Brunel Open Access Publishing Fund.Assessing the detrimental health effects of chemicals requires the extrapolation of experimental data in animals to human populations. This is achieved by applying a default uncertainty factor of 100 to doses not found to be associated with observable effects in laboratory animals. It is commonly assumed that the toxicokinetic and toxicodynamic sub-components of this default uncertainty factor represent worst-case scenarios and that the multiplication of those components yields conservative estimates of safe levels for humans. It is sometimes claimed that this conservatism also offers adequate protection from mixture effects. By analysing the evolution of uncertainty factors from a historical perspective, we expose that the default factor and its sub-components are intended to represent adequate rather than worst-case scenarios. The intention of using assessment factors for mixture effects was abandoned thirty years ago. It is also often ignored that the conservatism (or otherwise) of uncertainty factors can only be considered in relation to a defined level of protection. A protection equivalent to an effect magnitude of 0.001-0.0001% over background incidence is generally considered acceptable. However, it is impossible to say whether this level of protection is in fact realised with the tolerable doses that are derived by employing uncertainty factors. Accordingly, it is difficult to assess whether uncertainty factors overestimate or underestimate the sensitivity differences in human populations. It is also often not appreciated that the outcome of probabilistic approaches to the multiplication of sub-factors is dependent on the choice of probability distributions. Therefore, the idea that default uncertainty factors are overly conservative worst-case scenarios which can account both for the lack of statistical power in animal experiments and protect against potential mixture effects is ill-founded. We contend that precautionary regulation should provide an incentive to generate better data and recommend adopting a pragmatic, but scientifically better founded approach to mixture risk assessment. © 2013 Martin et al.; licensee BioMed Central Ltd.Oak Foundatio

Report from the EPAA workshop: In vitro ADME in safety testing used by EPAA industry sectors

AbstractThere are now numerous in vitro and in silico ADME alternatives to in vivo assays but how do different industries incorporate them into their decision tree approaches for risk assessment, bearing in mind that the chemicals tested are intended for widely varying purposes? The extent of the use of animal tests is mainly driven by regulations or by the lack of a suitable in vitro model. Therefore, what considerations are needed for alternative models and how can they be improved so that they can be used as part of the risk assessment process? To address these issues, the European Partnership for Alternative Approaches to Animal Testing (EPAA) working group on prioritisation, promotion and implementation of the 3Rs research held a workshop in November, 2008 in Duesseldorf, Germany. Participants included different industry sectors such as pharmaceuticals, cosmetics, industrial- and agro-chemicals. This report describes the outcome of the discussions and recommendations (a) to reduce the number of animals used for determining the ADME properties of chemicals and (b) for considerations and actions regarding in vitro and in silico assays. These included: standardisation and promotion of in vitro assays so that they may become accepted by regulators; increased availability of industry in vivo kinetic data for a central database to increase the power of in silico predictions; expansion of the applicability domains of in vitro and in silico tools (which are not necessarily more applicable or even exclusive to one particular sector) and continued collaborations between regulators, academia and industry. A recommended immediate course of action was to establish an expert panel of users, developers and regulators to define the testing scope of models for different chemical classes. It was agreed by all participants that improvement and harmonization of alternative approaches is needed for all sectors and this will most effectively be achieved by stakeholders from different sectors sharing data

Allocution d'ouverture de la célébration du bicentenaire de la naissance de Joseph Pelletier

Truhaut René. Allocution d'ouverture de la célébration du bicentenaire de la naissance de Joseph Pelletier . In: Revue d'histoire de la pharmacie, 77ᵉ année, n°281-282, 1989. Bicentenaire de la naissance de Joseph Pelletier (1788-1842) et 75e anniversaire de la fondation de la Société d'histoire de la Pharmacie. pp. 125-127

Allocution du Professeur René Truhaut

Truhaut René. Allocution du Professeur René Truhaut. In: Revue d'histoire de la pharmacie, 72ᵉ année, n°262, 1984. pp. 349-353

Allocution d'ouverture de la célébration du bicentenaire de la naissance de Joseph Pelletier

Truhaut René. Allocution d'ouverture de la célébration du bicentenaire de la naissance de Joseph Pelletier . In: Revue d'histoire de la pharmacie, 77ᵉ année, n°281-282, 1989. Bicentenaire de la naissance de Joseph Pelletier (1788-1842) et 75e anniversaire de la fondation de la Société d'histoire de la Pharmacie. pp. 125-127