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At least 91 records · Page 5Linked to original sources
PubMed1991

Determination of serum acetaminophen in emergency toxicology: evaluation of newer methods: Abbott TDx and second derivative ultraviolet spectrophotometry.

Newer methods for the determination of serum acetaminophen in emergency toxicology, the Abbott TDx immunoassay and second derivative ultraviolet spectrophotometry, were evaluated and compared to a high pressure liquid chromatographic procedure. The Abbott TDx immunoassay within-run and day to day precision yielded coefficients of variance below 2.7% and 7.2% respectively: Abbott TDx immunoassay results correlated well with those of high pressure liquid chromatographic in patient serums 15.0 to 333 mg/L acetaminophen; r2 = 0.954, n = 40. The Abbott TDx immunoassay assay was rapid, easy to perform, free of interferences from other drugs and exhibited no carryover from previous samples. The within run precision of the second derivative ultraviolet spectrophotometry method yielded coefficients of variance of less than 7.0%. Second derivative ultraviolet spectrophotometry results demonstrated good correlation with high pressure liquid chromatographic results in patient sera; r2 = 0.923, n = 40; however, performance deteriorated below 50.0 mg/L acetaminophen. Spectral interferences were noted at high concentrations of some drugs.

Acetaminophen↗
PubMed1993

Preclinical toxicology studies with azithromycin: genetic toxicology evaluation.

Azithromycin was subjected to a series of three in vitro and one in vivo genetic toxicology assays for the detection of drug-associated gene or chromosomal effects. In the Ames Salmonella typhimurium tester strains TA1535, TA1537, TA98 and TA100, the presence of azithromycin was not associated with any increase in the number of his- revertants. Urine from mice dosed with up to 200 mg/kg of azithromycin also had no effect on the number of revertants in these same strains suggesting the absence of mutagenic excretory products following oral exposure. When tested up to the cytotoxic level of 240 micrograms/ml, azithromycin caused no increase in the mutant frequency at the thymidine kinase locus of L5178Y/TK cells. Both the mammalian and microbial gene mutation assays included the presence of rat-liver postmitochondrial (S9) fraction for the detection of mutagenic biotransformation products. Mitogen-stimulated human lymphocytes cultured in the presence of 2.5-7.5 micrograms/ml azithromycin for 24 h or 30.0-40.0 micrograms/ml azithromycin for 3 h in the presence of rat S9 had chromosomal aberration frequencies that were no different than negative control cells even though slight to moderate mitotic suppression was associated with these concentrations. In vivo assessment of this compound was completed in male and female mice with a single oral dose of 200 mg/kg followed by sacrifice at 6, 24 or 48 h later and metaphase analysis of bone marrow for chromosomal aberrations. No statistically significant elevations of chromosomally aberrant cells were found. We conclude that azithromycin does not cause gene mutations in microbial or mammalian cells, or chromosomal aberrations in cultured human lymphocytes or in mouse bone marrow in vivo.

Animals↗
PubMed1984

The toxicological evaluation of tallysomycin s10b--biosynthetic tallysomycin derivative.

Tallysomycin S10b, a biosynthetic derivative of tallysomycin B, was subjected to intravenous toxicologic studies in mice and dogs. LD50 and LD10 values from lethality studies in mice were utilized to establish dose levels for single and five daily dose toxicity studies in mice and dogs. Nephrotoxicity was the most consistent and prominent drug-related alteration in single and multiple dose studies in both species and was considered the dose limiting toxicity. Other toxicities included pulmonary toxicity, lymphopenia and necrosis of extremities in mice and dogs and testicular degeneration and focal vacuolation of adrenal cortical cells in the dog. Bleomycin was administered to dogs as a reference control agent at a single dose of 270 mg/m2 which was approximately equivalent to the highest tallysomycin S10b dose of 240 mg/m2. Tallysomycin S10b showed a greater nephrotoxic potential than bleomycin at earlier time periods. However, at termination there was no meaningful difference in the degree of chronic nephrotoxicity. The pulmonary toxicity of both drugs was comparable.

Animals↗
PubMed1976

Toxicological evaluation and pharmacokinetic profile of beta-hydroxypropionitrile in rats.

Beta-hydroxypropionitrile (beta-HPN) was incorporated in the drinking water of rats in order to define the toxicological effects associated with repeated daily exposure to this compound. Parameters evaluated were appearance and demeanor, mortality, body weight, food consumption, water consumption, hematology, terminal organ weights and organ to body weight ratio, and gross and microscopic pathology of tissues. No untoward effects were associated with the ingestion of beta-HPN at the dose levels utilized.

Animals↗
PubMed2002

Toxicological evaluation of Catha edulis leaves: a long term feeding experiment in animals.

In this study the long term (6 months) toxicological effect of varying levels of Catha edulis leaves were examined on the plasma concentration of liver enzymes as well as the histopathology of tissue sections of the liver. Both biochemical and histopathological data presented demonstrate signs of C. edulis toxicity. Our results show a significant increase in plasma levels of Alkaline phosphatase (ALP), Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) with all levels of C. edulis leaves tested and throughout the treatment period. The increase of ALP was more prominent than both ALT and AST at the higher level of 30%. Plasma levels of AST though were only moderately increased at the higher level of 30% at the early stage of treatment (3 months) it significantly increased with all levels of C. edulis leaves in the long term (4-6 months). In addition, a time-dependent gradual increase in indirect bilirubin with a concomitant decrease in direct bilirubin levels were observed with the lower level of C. edulis (10%) with no signs of haemolysis. Histopathology of tissue sections of liver display evidences of increasing chronic inflammation with porto-portal fibrosis in the tissue sections obtained from animals treated with both 20 and 30% C. edulis.

Alanine Transaminase↗
PubMed1995

The preclinical toxicological evaluation of sumatriptan.

1 Sumatriptan is a potent and selective 5-HT1 receptor agonist marketed for the treatment of migraine by both oral and subcutaneous routes. An extensive toxicological programme employing high doses of sumatriptan was carried out in a range of animal species. The studies evaluated both the local and systemic tolerance to single and repeated dosing, effects on all stages of reproduction, as well as the genotoxic and oncogenic potential of sumatriptan. 2 The administration of relatively high single and repeated doses of sumatriptan was well tolerated by both rodents and dogs by the oral, subcutaneous and intravenous routes. Behavioural effects, suggestive of involvement of the central nervous system, were the most obvious result of such doses and were generally more pronounced in dogs than rodents. The reason for this may be related to the higher plasma concentrations of the drug achievable in dogs. Additional observations restricted to dogs, were transient, and included tachycardia, facial oedema and breaks in the continuity of secretion films on the corneal surface. A tendency for an increase in weight gain was seen for rats, while a slight decrease was usually seen for dogs. The only pathological changes related to treatment with high concentrations of sumatriptan consisted of local reactions at the site of subcutaneous administration. 3 Sumatriptan is an indole; the structures of this chemical class show varying propensities for nitrosation. However, appropriate testing with sumatriptan failed to identify any mutagenic nitroso compounds. 4 Sumatriptan was neither genotoxic nor oncogenic. 5 Reproductive studies demonstrated that sumatriptan was not teratogenic and had no effect on peri- and postnatal development. Some embryotoxicity was observed, but only at maternally toxic doses. A slight decrease in the success of insemination was also noted at high oral doses in rats. 6 Results of the toxicological programme performed in support of migraine therapy with sumatriptan provide good assurance of safety for subcutaneous and oral use.

Administration, Oral↗
PubMed2002

Toxicological evaluation of chemical mixtures.

This paper addresses major developments in the safety evaluation of chemical mixtures during the past 15 years, reviews today's state of the art of mixture toxicology, and discusses challenges ahead. Well-thought-out tailor-made mechanistic and empirical designs for studying the toxicity of mixtures have gradually substituted trial-and-error approaches, improving the insight into the testability of joint action and interaction of constituents of mixtures. The acquired knowledge has successfully been used to evaluate the safety of combined exposures and complex mixtures such as, for example, the atmosphere at hazardous waste sites, drinking water disinfection by-products, natural flavouring complexes, and the combined intake of food additives. To consolidate the scientific foundation of mixture toxicology, studies are in progress to revisit the biological concepts and mathematics underlying formulas for low-dose extrapolation and risk assessment of chemical mixtures. Conspicuous developments include the production of new computer programs applicable to mixture research (CombiTool, BioMol, Reaction Network Modelling), the application of functional genomics and proteomics to mixture studies, the use of nano-optochemical sensors for in vivo imaging of physiological processes in cells, and the application of optical sensor micro- and nano-arrays for complex sample analysis. Clearly, the input of theoretical biologists, biomathematicians and bioengineers in mixture toxicology is essential for the development of this challenging branch of toxicology into a scientific subdiscipline of full value.

Air Pollutants↗
PubMed1985

[The toxicologic evaluation of biomaterials. 1. Results of biomaterial tests in cultures of human amnion epithelial cells and human fibroblasts].

Cell cultures are a highly sensitive toxicological model used also for the testing of biomaterials. Beside the safety tests provided in the Pharmacopoeia of GDR cultures from human amnionepithelial cells and fibroblasts are used. The paper reports the results of some methodical investigations concerning the procedure of extraction of biomaterials, the evaluation of test results and the comparison with the results of other biological tests.

Amnion↗
PubMed1999

Toxicological evaluation of the new calcium antagonist VULM 993.

The tolerance of the new calcium antagonist VULM 993 was investigated in a series of toxicological studies. The following results were obtained: the maximum tolerated oral dose in acute toxicity was 10,000 mg/kg for mice and 6600 mg/kg for rats, for venous administration it was 26.1 mg/kg in mice and 32.2 mg/kg in rats. In subacute oral toxicity test in rats, VULM 993 showed no toxic effect up to 300 mg/kg/d. The drug was not teratogenic in rats (5, 50 or 250 mg/kg/d, p.o.). VULM 993 did not show any positive response in tests for genotoxicity in vitro. Transplacental study of VULM 993 in rabbits indicated active placental barrier function in the late stage of pregnancy. The toxicological profile of VULM 993 is characterised by a high tolerance in all relevant species of experimental animals, and no biologically significant mutagenic potential was recorded.

Administration, Oral↗
PubMed2004

[Clinical and toxicological evaluation of fatal poisoning with amphetamine derivative--MDMA, ecstasy (3,4-methylenedioxymethamphetamine)].

Intoxications with amphetamine derivatives represent an important problem of clinical and forensic toxicology. Even if distribution of the drug group has been legally forbidden, they continue to pose serious threats, linked to their uncontrolled administration which frequently leads to lethal intoxications. We present a case of intoxication in a 17-year-old male with amphetamine derivate--MDMA, Ecstasy. Clinical analysis documented an acute multi-organ failure, in particular pronounced hepatic and renal insufficiency, disseminated intravascular clotting (DIC). The comprehensive diagnosis and resulting discharge abstract of the acute poisoning were confirmed by postmortem investigations.

Acute Kidney Injury↗
PubMed2000

Toxicological evaluation of commercial mineral water bottled in polyethylene terephthalate: a cytogenetic approach with Allium cepa.

The aim of this study was to ascertain the possible toxicological effects of chemicals released into mineral water packaged in polyethylene terephthalate (PET) bottles. Two commercial mineral waters, bottled both in PET and glass and stored under different conditions, were examined using the Allium cepa test. The influence of the water samples on macroscopic (root length, colour and form) and microscopic (root tip mitotic index, chromosome aberrations) parameters was examined. The water samples were analysed after: (A) controlled-condition storage (no direct light exposure and 18 +/- 2 degrees C), (B) storage at 40 degrees C for 10 days, in the dark (migration test in accordance with 82/711/EEC), and (C) exposure to sunlight and varying temperatures (18-38 degrees C, mean temperature 25 +/- 3 degrees C). The two water samples bottled in PET induced cytogenetic aberrations regardless of the storage conditions. These signs of toxicity were evident even only 8 weeks after bottling, which is well within the recommended expiry date. Storage conditions were very important, as is suggested by the finding that chromosomal aberrations were particularly apparent after exposure to direct sunlight. However, as plant systems are not considered as primary screening tools by current international guidelines for mammalian systems, extrapolation of the results from this test system to other systems and, eventually, to human beings should be based on results from a battery of assays covering various metabolic pathways.

Chromosome Aberrations↗
PubMed2003

Toxicological evaluation of honey as an ingredient added to cigarette tobacco.

A tiered testing strategy has been developed to evaluate the potential for new ingredients, tobacco processes, and technological developments to increase or reduce the biological activity that results from burning tobacco. In the manufacture of cigarettes, honey is used as a casing ingredient to impart both aroma and taste. The primary objective of this document is to summarize and interpret chemical and toxicological studies that have been conducted to evaluate the potential impact of honey on the biological activity of either mainstream cigarette smoke or cigarette smoke condensate. As part of ongoing stewardship efforts, cigarettes produced with honey (5% wet weight) as an alternative to invert sugar in tobacco casing material were subjected to extensive evaluation. Principal components of this evaluation were a determination of selected mainstream smoke constituent yields, Ames assay, sister chromatid exchange assay in Chinese hamster ovary cells, a 30-wk dermal tumor promotion evaluation of cigarette smoke condensate in SENCAR mice, and a 13-wk inhalation study of cigarette smoke in Sprague-Dawley rats. Comparative analytical evaluations demonstrated that the substitution of honey for invert sugar as a casing material in cigarettes had no significant impact on mainstream smoke chemistry. In addition, in vitro and in vivo studies demonstrated that cigarettes containing tobacco cased with honey had comparable biological activity to cigarettes containing invert sugar. Collectively, these data demonstrate that the use of honey as an alternative casing material in the manufacture of cigarettes does not alter the potential toxicity of cigarette smoke condensate (CSC) or cigarette smoke; therefore the use of honey as an ingredient added to cigarette tobacco is acceptable from a toxicological perspective.

9,10-Dimethyl-1,2-benzanthracene↗