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At least 649 records · Page 36Linked to original sources
PubMed2003

The use of a non-lethal tool for evaluating toxicological hazard of organochlorine contaminants in Mediterranean cetaceans: new data 10 years after the first paper published in MPB.

In the Mediterranean Sea, top predators, and particularly cetacean odontocetes, accumulate high concentrations of organochlorine contaminants and toxic metals, incurring high toxicological risk. In this paper we investigate the use of the skin biopsies as a non-lethal tool for evaluating toxicological hazard of organochlorines in Mediterranean cetaceans, presenting new data 10 years after the paper published by Fossi and co-workers [Mar. Poll. Bull. 24 (9) (1992) 459] in which this new methodology was first presented. Some organochlorine compounds, now with worldwide distribution, are known as endocrine disrupting chemicals (EDCs). Here the unexplored hypothesis that Mediterranean cetaceans are potentially at risk due to organochlorines with endocrine disrupting capacity is investigated. High concentrations of DDT metabolites and PCB congeners (known as EDCs) were found in the different Mediterranean species (Stenella coeruleoalba, Delphinus delphis, Tursiops truncatus and Balaenoptera physalus). In this paper we also propose benzo(a)pyrene monooxygenase (BPMO) activity in marine mammal skin biopsies (non-lethal biomarker) as a potential indicator of exposure to organochlorines, with special reference to the compounds with endocrine disrupting capacity. A statistically significant correlation was found between BPMO activity and organochlorine levels (DDTs, pp(')DDT, op(')DDT, PCBs and PCB99) in skin biopsies of males of B. physalus. Moreover a statistical correlation was also found between BPMO activity and DDT levels in skin biopsies of the endangered Mediterranean population of D. delphis. These results suggest that BPMO induction may be an early sign of exposure to organochlorine EDCs and can be used for periodic monitoring of Mediterranean marine mammal toxicological status.

Animals↗
PubMed1997

Structural and mechanistic bases for the induction of mitotic chromosomal loss and duplication ('malsegregation') in the yeast Saccharomyces cerevisiae: relevance to human carcinogenesis and developmental toxicology.

MultiCASE has the ability to automatically determine the structural features responsible for the biological activity of chemicals. In the present study, 93 chemicals tested for their ability to induce chromosomal 'malsegregation' in the yeast Saccharomyces cerevisiae were analyzed. This 'malsegregation' mimics molecular events that occur during human development and carcinogenesis resulting in an effective loss of one chromosome of an autosomal pair and duplication of the homologue. Structural features associated with the ability to induce such chromosome loss and duplication were identified and compared with those obtained from examination of other toxicological data bases. The most significant structural similarities were identified between the induction of chromosomal malsegregation and several toxicological phenomena such as cellular toxicity, induction of sister chromatid exchanges in vitro and rodent developmental toxicity. Very significant structural similarities were also found with systemic toxicity, induction of micronuclei in vivo and human developmental toxicity. Less significant structural overlaps were found between yeast malsegregation and rodent carcinogenicity, DNA reactivity and mutagenicity, and the induction of chromosome aberrations in vitro and sister chromatid exchanges in vivo. These overlaps may indicate mechanistic similarities between the induction of chromosomal malsegregation and other toxicological phenomena. The predictivity of the SAR model derived from the present data base is relatively low, however. This may be merely a reflection of the small size and composition of the data base, however, further analyses suggest that it reflects primarily the multiple mechanisms responsible for the induction of chromosomal malsegregation in yeast and the complexity of the phenomenon.

Carcinogens↗
PubMed1997

Commentary on the application of (Q)SAR to the toxicological evaluation of existing chemicals.

For ethical and financial reasons it is impossible to perform thorough toxicological testing for all of the more than 100,000 substances registered in the European Inventory of Existing Substances. It was therefore investigated whether the application of (quantitative) structure-activity relationships (QSAR) with commercially available computer programs could predict the toxicological profile and help identify those substances requiring priority toxicological testing. Whereas predictions with respect to complex endpoints such as carcinogenicity, chronic toxicity and teratogenicity are still disappointing, more reliable predictions should be forthcoming in the immediate future for sensitisation, mutagenicity and genotoxicity endpoints.

Carcinogenicity Tests↗
PubMed1998

Toxicological evaluation of constructed wetland habitat sediments utilizing Hyalella azteca 10-day sediment toxicity test and bacterial bioluminescence.

A toxicological evaluation was conducted on wetland habitats created as a result of run-off from agricultural areas. These temporary wetlands were created by using drop pipes as a means of reducing erosional cutting in agricultural fields. Toxicity bioassays utilizing bacterial bioluminescence and Hyalella azteca were used to assess sediment pore water and whole sediment, respectively. Inhibition of bacterial bioluminescence was initially used to determine relative toxicities of pore water from ten wetland sites. Constructed wetland sites were compared to the University of Mississippi Biological Field Station, a relatively pristine reference site. The H. azteca ten day sediment toxicity test was utilized to assess sediment from four selected sites using survival and growth as toxicological endpoints. Results from the toxicological evaluation, along with extensive ecological evaluations, were used to assess the best approach for implementation of temporary wetland habitats with existing agricultural practices.

Agriculture↗
PubMed2004

Direct and interacting toxicological effects on the waterflea (Daphnia magna) by natural organic matter, synthetic humic substances and cypermethrin.

Humic substances are the main component of dissolved organic matter in all aquatic ecosystems, comprising a variety of molecular structures and functional groups. They bind organic pollutants and metals, thereby decreasing the bioavailability and consequently the toxicity of these substances in most instances. Recent studies also describe direct interactions and effects on organisms. Current studies also show that in some cases mitigation effects are stronger at lower concentrations of natural organic matter (NOM) and that toxicity increases with increased NOM concentrations. We hypothetise that at higher concentrations the mitigating effects are overlayed by direct effects of NOM themselves, thus these aspects were investigated in combination. So, on the one hand, this study demonstrates direct effects on toxicological parameters and activities of transformation enzyme systems of Daphnia magna, provoked by two NOM and one synthetic humic-like substance, HS1500. On the other hand, capacities of NOM and synthetic HS1500 to mitigate effects of the insecticide cypermethrin were investigated. Taken together, mitigation effects were overlayed by direct own effects of the NOM and HS1500. The NOM used were isolates from Suwannee River (XAD, Spring 2000) and from streams of the Svartberget forest (reverse osmosis, Spring 2000). The HS1500 was synthetically produced by radicalic autoxidation of hydroquinones. Suwannee River NOM at concentrations between 50 and 100 mg/l, and HS1500 (10-50 mg/l), but not Svartberget NOM increased immobility and lethality of the daphnids. All elevated the activity of the soluble glutathione S-transferase from 0.5 mg/l (HS1500), 1.0 mg/l (Suwannee River NOM) and 10 mg/l (Svartberget NOM) onwards, the microsomal glutathione S-transferase did not react. The glutathione peroxidase tended to increase. In the single exposure, the insecticide cypermethrin increased all toxicological parameters, elevated soluble and tendentially microsomal glutathione S-transferase activity between 0.001 and 1.0 microg/l and tendentially increased glutathione peroxidase. In contrast to that, 50 mg/l of the NOM and HS1500 did not mitigate toxicological effects. HS1500 in combination with cypermethrin even increased immobility, compared to cypermethrin alone. Increase of the NOM or HS1500 concentrations in combination with cypermethrin did not increase mitigation as seen in the activity of soluble glutathione S-transferases, activities of microsomal glutathione S-transferase and glutathione peroxidase even decreased, relative to control, which can be a hint of enzyme disfunction or further damages in the cell. An increase of concentration did not increase mitigation. Mitigation was higher at lower NOM or HS1500 concentration, probably as a consequence of the direct effects caused by themselves. Consequently, direct effects are relevant for analysing the mitigation qualities.

Animals↗
PubMed1996

Future approaches to genetic toxicology risk assessment.

Short-term genetic toxicology tests were developed for the purpose of identifying chemical carcinogens in the environment. After two decades of development and validation, the tests are well-established in routine testing schemes, but our views of their utility for safety evaluation have undergone re-assessment. The correlation between identified mutagens and identified carcinogens has turned out to be significantly less than one. Processes or mechanisms that are not directly genotoxic appear to play a role in carcinogenesis. While short term test data are still components of the assessment of carcinogenic risk, genetic damage also has been recognized as important in its own right, in relation to heritable genetic risk and other health-related effects, such as aging, reproductive failure and developmental toxicity. The revolution in molecular biology and genetic analysis occurring over the past 20 years has contributed to the wealth of new information on the complexities of cell regulation, differentiation, and the carcinogenic process. These technologies have provided new experimental approaches to genetic toxicology assessments, including transgenic cell and animal models, human monitoring, and analysis of macromolecular interactions at environmentally relevant exposures. The potential exists for the development of more efficient and more relevant genetic toxicology testing schemes for use assessing human safety. A delineation of contemporary needs, a modern view of the elements of cancer induction, and an examination of new assays and technologies may provide a framework for integrating new approaches into current schemes for evaluating the potential genetic and carcinogenic risk of environmental chemicals.

Animals↗
PubMed1990

Effective use of analytical laboratories for the diagnosis of toxicologic problems in small animal practice.

The increasing sophistication of toxicologic analyses offered by veterinary diagnostic laboratories provides the practitioner with a valuable resource for the diagnosis of companion and exotic animal toxicoses. The availability of such testing is a valuable service that can be offered to veterinary clientele. Appropriate and timely toxicologic testing may permit more successful treatment of affected patients and protect animals and humans from hazardous exposure that might occur if a responsible toxicant goes unrecognized. Perhaps the most critical point to keep in mind, however, is that no matter how sophisticated the toxicologic laboratory is, a correct diagnosis is dependent upon the submission of appropriate biologic and environmental samples.

Animals↗
PubMed1986

Serum alcohol levels, toxicology screens, and use of the breath alcohol analyzer.

The emergency physician sees a large number of patients with problems related to the ingestion of alcohol, drugs, and toxins, and must be prepared to deal with them in an efficient and cost-effective manner. This article discusses a rationale for ordering serum alcohol levels and toxicology screens, as well as use of the breath alcohol analyzer. A serum alcohol level should be reserved for patients in whom the alcohol level is necessary to confirm a diagnosis or to guide treatment. An alcohol level is indicated when alcohol use is combined with a significant alteration in mental status, multiple drug overdose, head injury, coma, major trauma, seizures, or psychosis. The breath alcohol analyzer is useful when rapid determination of alcohol levels is desired, particularly with coma or coexisting head trauma. A low or negative level in this case rapidly alerts the physician to the presence of another condition that may require additional testing. Toxicology screening should be performed when suspected drug or toxin ingestion is combined with coma, convulsions, head injury with altered mental status, unstable vital signs, alterations in acid-base or electrolyte status, or psychosis. The screen also may be used to determine the need for a specific antidote or means of increasing excretion of a toxin, or to determine the presence of a drug that should be quantified to guide management. Open communication with the laboratory and the use of rapid screening tests markedly increase the benefit of toxicology screening.

Absorption↗
PubMed1998

The experimental toxicology of tramadol: an overview.

The experimental toxicological findings of tramadol are reviewed and discussed. Tramadol is a centrally acting analgesic. In acute toxicity studies, LD50 values are estimated to be around 300-350 mg/kg body weight (rat, mouse, oral administration). After intravenous administration the LD50 values ranged from 50 to 100 mg/kg body weight. In subacute and chronic toxicity studies, clinical signs of intoxication are mainly behavioural disorders and convulsions, beginning at dose levels of 25 mg/kg. Clinical pathological alterations or morphological lesions, in particular neuropathological findings were not detected. Overall, the battery of mutagenicity studies shows no evidence of a genotoxic risk to man. Reproductive and developmental toxicity investigations and carcinogenicity studies were without substance-dependent findings. Toxicological and toxicokinetical data of both enantiomers did not show biologically relevant deviations in comparison to the data on tramadol. The toxicological characteristic of this compound is demonstrated.

Analgesics, Opioid↗
PubMed2001

Behavioral and pharmaco-toxicological study of Papaver rhoeas L. in mice.

A lyophilized ethanolic aqueous extract of Papaver rhoeas petals was evaluated for its behavioral and pharmaco-toxicological effects in mice and its chemical composition was studied using thin layer chromatography (TLC). In this study, chemical analysis by TLC showed that the petals contain some anthocyanins, whereas no alkaloids were detected. The toxicological effect of alcoholic and aqueous plant extract administered intraperitoneally was determined in mice. The toxicological results obtained indicated that 2000 mg/kg is LD10 and 4000 mg/kg is LD50. Behavioral and pharmacological studies of ethanolic and aqueous extract showed that the plant extract reduced locomotory, exploratory and postural behavior of mice. This was evaluated through two specific behavioral tests; a non-familiar environment test (the Staircase test) and a familiar environment test (Free exploratory test). These behavioral and pharmacological effects are more pronounced when the solvent used for extraction is 10% ethanol and is not antagonized by benzodiazepines, opioids, dopaminergic and cholinergic compounds (flumazenil, naloxone, sulpuride and atropine). The plant extract did not induce sleep in mice after treatment with an infrahypnotic dose of pentobarbital. This finding shows that the plant extract has a sedative effect at a 400 mg/kg dosage.

Alkaloids↗
PubMed2000

Contraceptive evaluation and toxicological study of aqueous extract of the seeds of Carica papaya in male rabbits.

The contraceptive evaluation and toxicological effects of the aqueous extract of the seeds of Carica papaya in adult male rabbits have been reported. Thirty adult male rabbits were divided into five groups of six animals each; Group I, control; Groups II-V were administered orally with aqueous extract of the seeds of C. papaya at doses of 20, 50, 75 and 100 mg/kg per day for 150 days, respectively. The body weight, reproductive organs weight, semen analysis, semen biochemistry, toxicological profiles and the fertility status have been recorded. The aqueous extract failed to exhibit contraceptive effects at any of the dose regimens tested, contrary to the observations made in the previous studies. Unaltered toxicological profiles indicated that the drug was free of side effects. The results suggest that the failure of contraceptive effects may be due to species specificity, relative resistance of the animals to the drug or lack of potency of the extract due to factors generally affect biological activity of the plant preparations.

Animals↗
PubMed2001

External quality assessment of laboratory performance in analysis of toxicological cases.

A mean of 44 members of the United Kingdom national external quality assessment scheme (UKNEQAS) for toxicology reported analytical findings on 10 toxicological cases circulated between December 1995 and February 2000. Material distributed usually consisted of a 5ml blood and a 20ml urine sample simulated by quantitative addition of drugs and their metabolites to material donated by volunteers and patients. The samples were accompanied by a brief outline of the circumstances surrounding the case. Laboratories were requested to report their analytical findings, list methods of analysis, and provide interpretation of their findings. The mean overall success rate for identification of drugs or their pharmacological group was 76%, failure being largely by laboratories providing an immunoassay-based screening service for a fixed range of drug groups. The latter laboratories indicated that cases would be referred to regional toxicology centres for further investigation or confirmation. The coefficient of variation of measurements was <7% for routine analytes, such as ethanol and paracetamol, but 26-44% for tricyclics and opiates. There were 3% false positive reports. The quantity and content of interpretative comment provided by the laboratories was very variable. A number provide nothing in addition to the analytical result.

Adolescent↗
PubMed1992

Search for the mechanism of toxicity of dioxins. A lesson in toxicology.

The development of modern toxicology was strongly influenced by parallel evolutions of sister disciplines as well as regulatory requirements. This led to an overemphasis of some areas of toxicology while other aspects of it experienced at least a temporary benign neglect. The author of this paper believes that the few and far between successes in elucidating the mechanism of toxicity of chemicals are related to this uneven approach to a very complex problem. Based on one of the most important and controversial contemporary issues in toxicology, viz. that of dioxins, it is argued that by a systematic step-wise use of methodologies borrowed from sister disciplines, our capabilities of elucidating the mechanism of action of toxicants can be considerably improved.

Animals↗
PubMed2001

Critical effect sizes in toxicological risk assessment: a comprehensive and critical evaluation.

A key issue in toxicological risk assessment is determining the effect level below which there is no reason for concern. In the Benchmark approach, this breaking point between adverse and non-adverse is called the critical effect size (CES). This study aimed to investigate the possibilities to determine CESs for toxicological effect parameters commonly used in human risk assessment and includes a literature review and an opinion analysis among European toxicologists. The results indicate that the current knowledge is insufficient to define CESs for all individual parameters. Furthermore, the use of a single universal CES seems no option. It is concluded that it is not yet possible to reach international consensus on CESs for most toxicological parameters. However, every parameter for which consensus on the CES is reached is a step forward, because this can facilitate discussions on the adversity and relevance of certain changes in that parameter, irrespective of the method applied in risk assessment.

Journal Article↗
PubMed2003

Studies on the metabolism and toxicological detection of the Eschscholtzia californica alkaloids californine and protopine in urine using gas chromatography-mass spectrometry.

Eschscholtzia californica preparations are in use as phytopharmaceuticals and as herbal drugs. Studies are described on the metabolism and the toxicological analysis of the Eschscholtzia californica alkaloids californine and protopine in rat urine using gas chromatography-mass spectrometry. The identified metabolites indicated that californine is extensively metabolized by N-demethylation and/or single or double demethylenation with consecutive catechol-O-methylation of one of the hydroxy groups. Protopine, however, only undergoes extensive demethylenation of the 2,3-methylenedioxy group followed by catechol-O-methylation. All phenolic hydroxy metabolites were found to be partly conjugated. The authors' systematic toxicological analysis procedure using full-scan gas chromatography-mass spectrometry after acid hydrolysis, liquid-liquid extraction and microwave-assisted acetylation allowed the detection of the main metabolites of californine and protopine in rat urine after a dose which should correspond to that of drug users. Therefore, use of Eschscholtzia californica preparations should also be detectable in human urine by the authors' systematic toxicological analysis procedure.

Animals↗
PubMed1999

Development of a new in vitro system for continuous in vitro exposure of lung tissue to complex atmospheres: application to diesel exhaust toxicology.

The purpose of this study was the development of a new incubation system that can allow continuous exposure of lung tissue to complex atmospheres as a tool for the assessment of aerial environmental lung toxicology. To assess the pertinence of this new exposure system, we studied the impact of diesel engine exhausts as a complex atmosphere containing both gaseous and particulate fractions and have been able to discriminate between the toxicological impacts of the gaseous phase and particulate matter from diesel exhausts. Continuous flow-through rotating chambers with controlled PO2, pCO2, and hygrometry have been designed in which lung slices are positioned in rolling inserts that allow free access of atmosphere to the exposed lung tissue. Under control conditions, cell viability was preserved for at least 48 h as assessed by intracellular ATP, GSH, and K+ levels and slice O2 consumption levels. Short-term exposure (1 h) to diesel whole exhausts did not affect intracellular potassium or slice O2 consumption, while intracellular ATP and GSH levels were markedly decreased. Exposure to filtered exhausts showed less marked effects on both ATP and GSH levels. Superoxide dismutase activity was decreased in a similar way by both total and filtered exhausts while Se(+)-dependent glutathione peroxidase activity was induced by filtered exhausts to a larger extent than after total exhaust exposure, showing different response patterns of lung tissue after exposure to whole or filtered exhausts. In conclusion, this newly designed model opens a promising area in in vitro environmental lung toxicology testing.

Adenosine Triphosphate↗
PubMed1996

Characterization of AUCs from sparsely sampled populations in toxicology studies.

PURPOSE: The objective of this work was to develop and validate blood sampling schemes for accurate AUC determination from a few samples (sparse sampling). This will enable AUC determination directly in toxicology studies, without the need to utilize a large number of animals. METHODS: Sparse sampling schemes were developed using plasma concentration-time (Cp-t) data in rats from toxicokinetic (TK) studies with the antiepileptic felbamate (F) and the antihistamine loratadine (L); Cp-t data at 13-16 time-points (N = 4 or 5 rats/time-point) were available for F, L and its active circulating metabolite descarboethoxyloratadine (DCL). AUCs were determined using the full profile and from 5 investigator designated time-points termed "critical" time-points. Using the bootstrap (re-sampling) technique, 1000 AUCs were computed by sampling (N = 2 rats/point, with replacement) from the 4 or 5 rats at each "critical" point. The data were subsequently modeled using PCNONLIN, and the parameters (ka, ke, and Vd) were perturbed by different degrees to simulate pharmacokinetic (PK) changes that may occur during a toxicology study due to enzyme induction/inhibition, etc. Finally Monte Carlo simulations were performed with random noise (10 to 40%) applied to Cp-t and/or PK parameters to examine its impact on AUCs from sparse sampling. RESULTS: The 5 time-points with 2 rats/point accurately and precisely estimated the AUC for F, L and DCL; the deviation from the full profile was approximately 10%, with a precision (%CV) of approximately 15%. Further, altered kinetics and random noise had minimal impact on AUCs from sparse sampling. CONCLUSIONS: Sparse sampling can accurately estimate AUCs and can be implemented in rodent toxicology studies to significantly reduce the number of animals for TK evaluations. The same principle is applicable to sparse sampling designs in other species used in safety assessments.

Animals↗
PubMed2003

Measuring outcome in cocaine clinical trials: a comparison of sweat patches with urine toxicology and participant self-report.

AIMS: To evaluate the advantages of using a sweat patch (PharmCheck) for detecting cocaine abuse in cocaine-dependent patients participating in a clinical trial. The utility of the sweat patch was assessed from the following perspectives: the reliability and validity of quantitative sweat patch results, the possible degradation of cocaine to benzoylecgonine (BE) as a function of the length of time that a patch is worn, the completeness of the dataset yielded by thrice-weekly urine toxicology compared with thrice-weekly and weekly sweat patches, and the relative costs associated with sweat patch versus urine measures. DESIGN: Data were collected during a 10-week out-patient clinical trial in which participants wore two sweat patches, one applied every visit and one applied weekly. Urine samples were collected thrice weekly, as were self-reports of substance use. SETTING: A multi-site clinical trial conducted in Boston, Cincinnati and New York, USA. PARTICIPANTS: Twenty-seven participants with comorbid diagnoses of cocaine dependence and adult attention deficit disorder completed the study. MEASUREMENTS: Sweat patch and urine samples were analyzed by standard methods for cocaine and cocaine metabolites. FINDINGS: Quantitative sweat patch measures had good reliability in that the correlation between the weekly and per-visit patches was 0.96 (P < 0.0001). The concurrent validity, as judged by the correlation between quantitative urine BE levels and either weekly (0.76, P < 0.0001) or per-visit (0.73, P < 0.0001) cocaine sweat patch levels was reasonable. The correlation between the self-report of cocaine use and these same two patches, however, was lower (0.40, P < 0.05 and 0.30, P < 0.05, respectively). The results revealed no significant degradation of cocaine to BE associated with wearing the patch for a longer time. Finally, the per-visit patch provided cocaine use data on 80.5% of all study days (a total of 70), while urine toxicology and the weekly patch provided 77.4% and 76.1%, respectively. CONCLUSIONS: The present findings suggest that the PharmCheck patch might be an attractive alternative to urine toxicology for use as an outcome measure in cocaine clinical trials.

Adult↗