ABSTRACT
An evaluation was performed on the first group (41) of completed risk assessments for chemicals of the EU priority lists (Existing Chemicals; EC Regulation 793/93). The evaluation focussed on the conclusions of the risk assessments. The EU risk assessment process detected a high number of substances of concern. Furthermore priority chemicals may pose potential risks to the whole range of protection goals of the risk assessment. The predictability of the risk assessments for priority chemicals was investigated. Our a priori knowledge on possible risks of priority chemicals is found to be poor, especially for consumers. Both for environment and human health the potential risks were linked with a broad spectrum of use patterns. It is concluded that no industry category can in advance be excluded from performing risk assessments. For a great number of chemicals, additional testing was found to be needed to finalize the risk assessment. This evokes questions about the completeness of the current base-set, but also about the suitability of some of the submitted human health tests that should initially fulfil the base-set needs. The results of this evaluation are useful for ongoing discussions on risk assessment processes for chemicals.
Subject(s)
Hazardous Substances/toxicity , International Agencies/legislation & jurisprudence , European Union , Industry , Risk Assessment , Toxicity Tests/methodsABSTRACT
A fatality that was due to massive ingestion of the thioxanthene neuroleptic (Z)-cis-clopenthixol (zuclopenthixol, Z-CPT) is described. The total toxicological screening and the quantitation of both the ingested drugs and its inactive isomer (E)-trans-clopenthixol (E-CPT, produced by in vivo isomerization) in postmortem fluids and viscerae were produced by high-performance liquid chromatography (HPLC)-diode array detection. Drug confirmation was carried out by HPLC-mass spectrometry with an ionspray interface. Although death occurred 40 h after the drug intake, postmortem blood concentrations were 391 and 275 mg/mL for Z-CPT and E-CPT, respectively (50 to 100 times the usual therapeutic values). The cause of death was suicide, and the manner was acute neuroleptic overdosage.
Subject(s)
Antipsychotic Agents/poisoning , Chromatography, High Pressure Liquid/methods , Clopenthixol/poisoning , Adolescent , Antipsychotic Agents/pharmacokinetics , Body Fluids/metabolism , Clopenthixol/pharmacokinetics , Drug Overdose , Fatal Outcome , Female , Humans , Mass Spectrometry , Tissue Distribution/physiology , Viscera/metabolismABSTRACT
We report the first case in the literature of fatal betaxolol (Kerlone) self-poisoning. After a single-step liquid-liquid alkaline extraction, betaxolol was identified by a high-performance liquid chromatographic-diode array detection screening procedure and then quantitated in cardiac blood, heart, brain, muscle, spleen, stomach contents, duodenum contents, liver, and kidney. The blood betaxolol concentration was 36 mg/L.
Subject(s)
Adrenergic beta-Antagonists/poisoning , Betaxolol/poisoning , Suicide , Adrenergic beta-Antagonists/blood , Adrenergic beta-Antagonists/metabolism , Adult , Autopsy , Betaxolol/blood , Betaxolol/metabolism , Brain/metabolism , Chromatography, High Pressure Liquid , Female , Gastrointestinal Contents/chemistry , Humans , Kidney/metabolism , Liver/metabolism , Muscles/metabolism , Myocardium/metabolism , Reference Standards , Spleen/metabolism , Tissue DistributionABSTRACT
Determination of optical isomers is based on some molecule properties to have one or more chiral asymmetrical carbon center. Enantiomers can be resolved by high performance liquid chromatography (HPLC) with a chiral mobile phase additive, by change into diastereoisomers by derivatization or by separation on chiral column. We retained the last technique for the separation of seven beta-blockers (atenolol, alprenolol, labetalol, nadolol, oxprenolol, pindolol and propranolol) using an alpha 1-AGP column. Results indicate that the mobile phase was specific to each beta-blocker. The wavelength chosen was lambda = 225 nm and the flow rate was 0.9 ml/min. A part from that, determinations of isomers of propranolol and atenolol in different fluids biologicals were also achieved.
Subject(s)
Adrenergic beta-Antagonists/chemistry , Chromatography, High Pressure Liquid/methods , Pharmacopoeias as Topic , Adrenergic beta-Antagonists/isolation & purification , Adult , Atenolol/analysis , Atenolol/chemistry , Female , France , Humans , Male , Propranolol/analysis , Propranolol/chemistry , StereoisomerismABSTRACT
A high-performance liquid chromatographic method for the simultaneous determination of flunitrazepam and four metabolites, desmethylflunitrazepam (DMF), 7-aminodesmethylflunitrazepam (7-NH2DMF), 7-aminoflunitrazepam (7-NH2F) and 3-hydroxyflunitrazepam (3-OHF), in serum is described. The method involves a simple extraction from alkalinized plasma (pH 9.5) into diethyl ether-chloroform (80:20, v/v). Prazepam was used as an internal standard for the quantification of the five compounds. Separation was achieved with a 10 microns RSil CN column (300 x 3.9 mn I.D.). The detection wavelength was set at 242 nm. The limits of detection ranged from 2.5 to 5 micrograms/l with a limit of quantification of 10 micrograms/l for all analytes.
Subject(s)
Anti-Anxiety Agents/blood , Anti-Anxiety Agents/metabolism , Chromatography, High Pressure Liquid/methods , Flunitrazepam/blood , Flunitrazepam/metabolism , Anti-Anxiety Agents/chemistry , Flunitrazepam/chemistry , Hydrogen-Ion Concentration , Osmolar Concentration , Prazepam/blood , Reference Standards , Regression Analysis , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
Alimemazine, a phenothiazine derivative with the properties of antihistamines, was determined by a selective high-performance liquid chromatographic technique in blood and tissues from a postmortem case. The blood concentration of alimemazine was 6.52 micrograms/mL. The brain was the major site of drug deposition, and tissue distribution is discussed in light of the existing literature.
