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At least 91 records · Page 5Linked to original sources

PubMed2006

The relationship between observer-based toxicity scoring and patient assessed symptom severity after treatment for head and neck cancer. A correlative cross sectional study of the DAHANCA toxicity scoring system and the EORTC quality of life questionnaires.

BACKGROUND AND PURPOSE: Morbidity is an important issue in cancer research. The observer-based toxicity scoring system used by DAHANCA (the Danish head and neck cancer study group) has proved itself sensitive to differences in toxicity in a large randomised study, but like other toxicity scoring systems it has not been formally validated. Conversely, the EORTC quality of life questionnaire (QLQ) has been validated as a tool for collecting information about the consequences of disease and treatment on the well being of cancer patients. The purpose of this study was to examine the relationship between the two methods of side effect recording. PATIENTS AND METHODS: One hundred and sixteen recurrence free patients with laryngeal (n=44), pharyngeal (n=34) and oral cavity (n=38) cancer attending follow-up after radiotherapy (n=83) or surgery (n=33) completed EORTC C30, the core questionnaire concerning general symptoms and function and EORTC H&N35 the head and neck specific questionnaire. The attending physicians in the follow-up clinic evaluated and recorded DAHANCA toxicity scores on the same patients. RESULTS: The DAHANCA toxicity scoring system and the EORTC QLQ correlated with several clinical endpoints. The conceptually similar endpoints of the two methods correlated significantly. The objective endpoints of the DAHANCA scoring system were only correlated with quality of life endpoints to a very low degree. The DAHANCA toxicity scores had a low sensitivity (0.48-0.74) in detecting equivalent subjective complaints from the questionnaires and the observer-based scoring system severely underestimated patient complaints. A specific patient group where the DAHANCA score had a higher tendency to fail could not be detected. CONCLUSION: The DAHANCA toxicity score is an effective instrument in assessing objective treatment induced toxicity in head and neck cancer patients but insensitive and non-specific with regard to patient assessed subjective endpoints. This weakness seems inherent in an observer-based scoring system, and will probably also apply to newer ones like CTCAE 3.0.

Adult↗

PubMed2001

Metabolic, idiosyncratic toxicity of drugs: overview of the hepatic toxicity induced by the anxiolytic, panadiplon.

Preclinical drug safety evaluation studies, typically conducted in two or more animal species, reveal and define dose-dependent toxicities and undesirable effects related to pharmacological mechanism of action. Idiosyncratic toxic responses are often not detected during this phase in development due to their relative rarity in incidence and differences in species sensitivity. This paper reviews and discusses the metabolic idiosyncratic toxicity and species differences observed for the experimental non-benzodiazepine anxiolytic, panadiplon. This compound produced evidence of hepatic toxicity in Phase 1 clinical trial volunteers that was not predicted by rat, dog or monkey preclinical studies. However, subsequent studies in Dutch-belted rabbits revealed a hepatic toxic syndrome consistent with a Reye's Syndrome-like idiosyncratic response. Investigations into the mechanism of toxicity using rabbits and cultured hepatocytes from several species, including human, provided a sketch of the complex pathway required to produce hepatic injury. This pathway includes drug metabolism to a carboxylic acid metabolite (cyclopropane carboxylic acid), inhibition of mitochondrial fatty acid beta-oxidation, and effects on intermediary metabolism including depletion of glycogen and disruption of glucose homeostasis. We also provide evidence suggesting that the carboxylic acid metabolite decreases the availability of liver CoA and carnitine secondary to the formation of unusual acyl derivatives. Hepatic toxicity could be ameliorated by administration of carnitine, and to a lesser extent by pantothenate. These hepatocellular pathway defects, though not directly resulting in cell death, rendered hepatocytes sensitive to secondary stress, which subsequently produced apoptosis and hepatocellular necrosis. Not all rabbits showed evidence of hepatic toxicity, suggesting that individual or species differences in any step along this pathway may account for idiosyncratic responses. These differences may be roughly applied to other metabolic idiosyncratic hepatotoxic responses and include variations in drug metabolism, effects on mitochondrial function, nutritional status, and health or underlying disease.

Animals↗

PubMed2004

In vivo mechanisms of tissue-selective drug toxicity: effects of liver-specific knockout of the NADPH-cytochrome P450 reductase gene on acetaminophen toxicity in kidney, lung, and nasal mucosa.

Acetaminophen overdose causes toxicity in liver and extrahepatic tissues. Although it is well established that cytochrome P450 enzymes play a critical role in the metabolic activation of acetaminophen, it is not yet clear whether acetaminophen toxicity in extrahepatic tissues is a consequence of hepatic biotransformation. The aim of this study was to determine whether extrahepatic acetaminophen toxicity is altered in a mouse model that has liver-specific deletion of the NADPH-cytochrome P450 reductase (Cpr) gene. Liver-specific Cpr-null (Null) mice were resistant to acetaminophen hepatotoxicity, and they showed faster acetaminophen clearance than did wild-type mice at a toxic acetaminophen dose (400 mg/kg i.p.). However, when circulating acetaminophen levels were made equivalent in the two strains, the severity of extrahepatic acetaminophen toxicity was decreased in the Null relative to that in the wild-type mice in the lung, kidney, and lateral nasal glands, although not in the nasal olfactory and respiratory mucosa. In the lung and liver, the decreased acetaminophen toxicity was accompanied by substantial decreases in the formation of acetaminophen-protein adducts in the Null mice; adducts were not detected in other tissues examined. These results indicate that acetaminophen toxicity in the nasal mucosa is not dependent on hepatic microsomal P450-catalyzed metabolic activation and that acetaminophen toxicity in the lung, kidney, and lateral nasal glands is at least partly caused by liver-derived acetaminophen metabolites.

Acetaminophen↗

PubMed1998

Hyperfunctioning thyroid nodules in toxic multinodular goiter share activating thyrotropin receptor mutations with solitary toxic adenoma.

Toxic multinodular goiter is a cause of nonautoimmune hyperthyroidism and is believed to differ in its nature and pathogenesis from toxic adenoma. Gain-of-function mutations of the TSH receptor gene have been identified as a cause of toxic adenoma. The pathogenesis at the molecular level of hyperfunctioning nodules in toxic multinodular goiter has yet not been reported. Six patients with a single hot nodule within a multinodular goiter and 11 patients with toxic thyroid adenoma were enrolled in our study. At histology five hyperfunctioning nodules in multinodular goiters showed the features of adenomas, and one was identified as a hyperplastic nodule. The entire exon 10 of the TSH receptor gene was directly sequenced after PCR amplification from genomic DNA obtained from surgical specimens. Functional studies of mutated receptors were performed in COS-7 cells. Five out of 6 (83%) hyperfunctioning nodules within toxic multinodular goiters harbored a TSH receptor mutation. A TSH receptor mutation was also evident in the hyperfunctioning nodule that at histology had the features of noncapsulated hyperplastic nodule. Among toxic adenomas, 8 out of 11 (72%) nodules harbored a TSH receptor mutation. All the mutations were heterozygotic and somatic. Nonfunctioning nodules, whether adenomas or hyperplastic nodules present in association with hyperfunctioning nodules in the same multinodular goiters, had no TSH receptor mutation. All the mutations identified had constitutive activity as assessed by cAMP production after expression in COS-7 cells. Hyperfunctioning thyroid nodules in multinodular goiters recognize the same pathogenetic event (TSH receptor mutation) as toxic adenoma. Other mechanisms are implicated in the growth of nonfunctioning thyroid nodules coexistent in the same gland.

Adenoma↗

PubMed2006

Detoxifying toxicants: interactions between sulfide and iron toxicity in freshwater wetlands.

In many Dutch freshwater wetlands, concentrations of sulfate in the surface water and groundwater have increased. It is especially in peaty areas that this can lead to problems, including the reduction of sulfate to toxic sulfide. Our aquarium experiments showed that even low sulfide concentrations of 50 micromol/L are toxic to the freshwater macrophyte Nitella flexilis and the freshwater oligochaete Ophidonais serpentina. Sulfide toxicity can be modified by the availability of free iron in soil moisture or sediment from iron-rich groundwater discharge. The iron precipitates the sulfide, thereby immobilizing it and decreasing its toxicity. However, iron itself can be a toxicant as well. We found a detoxifying effect of moderate iron concentrations on sulfide toxicity, as well as a toxic effect of high iron concentrations on the growth of Potamogeton acutifolius. At the intermediate range, the formation of metal sulfides can simultaneously decrease metal and sulfide toxicity. Results of the experiments are discussed in relation to hydrological changes in freshwater wetlands.

Fresh Water↗

PubMed2006

Can highly hydrophobic organic substances cause aquatic baseline toxicity and can they contribute to mixture toxicity?

Effect concentrations for aquatic baseline toxicity generally decrease with increasing log octanol-water partition co-efficient (Kow) values of up to 5 to 6, whereas less is known about the baseline toxicity of organic chemicals with log Kow values above 6. A physicochemical analysis of the dissolution process for organic chemicals was combined with reported baseline toxicity data, leading to the following conclusions. First, no absolute hydrophobicity cutoff exists for baseline toxicity at a log Kow value of 6, because aquatic baseline toxicity for fish and algae was observed for chemicals with log Kow values greater than 6.5 and with effect concentrations less than 10 microg/L. Second, the baseline toxicity of hydrophobic organic substances was exerted at a relatively constant chemical activity of 0.01 to 0.1. Finally, organic chemicals with high melting points cannot provide sufficient chemical activity to exert baseline toxicity when considered as individual, pure chemicals. However, such substances are still expected to contribute to baseline toxicity when part of a complex mixture.

Organic Chemicals↗

PubMed2002

Evaluation of the effect of reactive sulfide on the acute toxicity of silver (I) to Daphnia magna. Part 2: toxicity results.

The protective effect of reactive sulfide against AgNO3 toxicity to Daphnia magna neonates was studied. Acute (48-h) toxicity tests were performed in the absence (<5 nM) and presence of low (approximately 25 nM) and high (approximately 250 nM) concentrations of zinc sulfide clusters under oxic conditions. In both the presence and the absence of sulfide, lower mean lethal concentration (LC50) values were observed when measured as opposed to nominal silver concentrations were used in calculations. This reflected the fact that measured total silver concentrations were lower than nominal concentrations due to losses of silver from solution observed during the experiment. High concentration (approximately 250 nM) of sulfide completely protected against toxicity up to the highest silver concentration tested (2 microg/L [19 nM]) with measured silver data. In the presence of environmentally realistic levels of sulfide (approximately 25 nM) in receiving waters, acute silver toxicity was reduced by about 5.5-fold. However, when filtered (0.45 microm) silver concentrations alone were considered, toxicity (48-h LC50) was similar in the absence (0.22 microg/L) and presence (0.28 microg/L) of sulfide. The difference between measured total and filtered silver was attributed to chemisorption of the metal sulfide onto the membrane filter and provides evidence that the toxic fraction of silver is that which is unbound to sulfide. Accumulation of silver was greater in daphnids exposed to silver in the presence of sulfide than in its absence, even though a toxic effect was not observed under these conditions. In this case, silver appears to be incorporated by daphnids rather than merely adsorbed on the surface. Our results point out the need to incorporate sulfide into the acute biotic ligand model and to assess its potentially large role in preventing chronic toxicity.

Adsorption↗

PubMed1996

Carnitine and choline derivatives containing a trimethylamine group prevent ammonia toxicity in mice and glutamate toxicity in primary cultures of neurons.

Carnitine prevents acute ammonia toxicity in animals. We propose that acute ammonia toxicity is mediated by activation of N-methyl-D-aspartate receptors and have shown that carnitine prevents glutamate neurotoxicity. The aim of this work was to assess whether other compounds containing a trimethylamine group are able to prevent ammonia toxicity in mice and/or glutamate toxicity in primary neuronal cultures. It is shown that betaine, trimethylamine-N-oxide, choline, acetylcholine, carbachol and acetylcarnitine prevent ammonia toxicity in mice. They also prevent glutamate but not N-methyl-D-aspartate neurotoxicity. Choline, acetylcholine and acetylcarnitine afford partial (approximately 50%) protection at nanomolar concentrations and nearly complete protection at micromolar concentrations. Trimethylamine-N-oxide, carbachol and betaine afford nearly complete protection at approximately 0.2 mM. The protective effect against glutamate neurotoxicity is prevented by 2-amino-3-phosphonopropionic acid, an antagonist of metabotropic glutamate receptors. Atropine, an antagonist of muscarinic receptors, prevents the protective effect of most of the above compounds against ammonia toxicity in mice and against glutamate toxicity in cultured neurons. These results support the idea that acute ammonia toxicity is mediated by activation of N-methyl-D-aspartate receptors and that glutamate neurotoxicity could be prevented by activating metabotropic glutamate receptors and/or muscarinic receptors.

Ammonia↗

PubMedDate not supplied

Mosquito coil smoke inhalation toxicity. Part I: validation of test approach and acute inhalation toxicity.

Burning mosquito coils indoors to repel mosquitoes is a common practice in many households in tropical countries. The evaluation and assessment of the inhalation toxicity of smoke emitted from mosquito coils appear to be particularly challenging due to the complex nature of this type of exposure atmosphere. The potential health implications of the gases, volatile agents and particulate matter emitted from burning coils or incense have frequently been addressed; however, state-of-the-art inhalation toxicity studies are scarce. The focus of this paper was comparatively to evaluate and assess the appropriateness and practical constraints of the whole-body versus the nose-only mode of exposure for inhalation toxicity studies with burning mosquito coils. With regard to the controlled exposure of laboratory animals to complex smoke atmospheres the nose-only mode of exposure had distinct advantages over the whole-body exposure, which included a rapid attainment of the inhalation chamber steady state, minimization of particle coagulation and uncontrolled adsorption of condensate onto the chamber surfaces. While in whole-body chambers a different kinetic behaviour of volatile and particulate constituents was found which caused inhomogeneous, i.e. artificially enriched atmospheres with volatile components at the expense of aerosols, the nose-only mode of exposure provided maximum exposure intensities without losses of the particulate phase of the exposure atmosphere. Collectively, the results obtained support the conclusion that the dynamic nose-only mode of exposure is experimentally superior to the quasistatic whole-body exposure mode which provides the least control over exposure atmospheres and the outcome highly contingent on selected experimental factors. Acute inhalation toxicity studies in rats suggest that the most critical metrics of exposure are apparently related to (semi)volatile upper respiratory tract sensory irritants, whilst the asphyxic component, carbon monoxide, plays a role only at overtly irritant exposure levels. However, this study was conducted at exposure concentrations much higher than encountered by people in residential settings and the effects observed under these conditions may not be relevant to hazards from exposures at common use levels. Neither an acute 8 h exposure of rats nor the 1 h sensory irritation study in mice and rats provided experimental evidence that irritant particle-related effects had occurred in the lower respiratory tract. In summary, the protocols devised evaluate and assess the acute inhalation toxicity of mosquito coil smoke demonstrating that the nose-only mode of exposure of rats to the smoke of mosquito coils is suitable to assess the toxic potency of different coils. The nose-only mode has clear advantages over the whole-body exposure mode. The inhalation studies conducted show unequivocally that acute toxic effects are difficult to produce with this type of product even under rigorous testing conditions.

Air Pollutants↗

PubMed1993

Isolation of the major component in white snakeroot that is toxic after microsomal activation: possible explanation of sporadic toxicity of white snakeroot plants and extracts.

Tremetone, the major toxic component in white snakeroot (Eupatorium rugosum Houtt) extracts, was isolated following an in vitro bioactivity assay. Microsomal activation was required to produce a product toxic to murine melanoma (B16F1) cells as well as five other mammalian cell cultures. The metabolic activation product(s) of tremetone is suspected to be responsible for the toxic activity of the plant. Tremetone is also smoothly converted to dehydrotremetone in the plant and cell free homogenates, and readily decomposes to dehydrotremetone in extracts. Dehydrotremetone is not toxic even after microsomal activation. The efficient conversion of tremetone to dehydrotremetone may explain why white snakeroot plant material and extracts have varied activities, and why a previous claim that tremetone was responsible for the toxic activity of white snakeroot was withdrawn. Rayless goldenrod extracts show the same toxic activity as white snakeroot and the toxic activity of rayless goldenrod is most likely due to tremetone.

Animals↗

PubMed2002

Direct toxicity assessment of wastewater: Baroxymeter, a portable rapid toxicity device and the industry perspective.

Direct toxicity assessment of wastewater is becoming necessary, and new legislation may render it compulsory for the water industry. At present such assessment is performed at a laboratory away from a site, at considerable cost, and results often come too late, after a toxic event has occurred and the toxin has been released into the environment. Some of the rapid toxicity tests available today require certain conditions to function properly, or their results do not always correlate with other methods. The objective of this study was to assess a portable device, the Baroxymeter, for its suitability as an instrument to test wastewater toxicity. The way the device works is based on monitoring respiration of a bacterial culture by pressure measurements and using respiration inhibition as a toxicity alert. It has been shown that it is possible to detect toxic substances such as 3,5-dichlorophenol and bronopol within 5 min from a 1-mL sample. The benefits and future applications of the Baroxymeter as a high-throughput, cost-effective alternative for toxicity screening are discussed in this article.

Bacterial Physiological Phenomena↗

PubMed2000

Priority assessment of toxic substances in life cycle assessment. Part I: calculation of toxicity potentials for 181 substances with the nested multi-media fate, exposure and effects model USES-LCA.

Toxicity potentials are standard values used in life cycle assessment (LCA) to enable a comparison of toxic impacts between substances. In most cases, toxicity potentials are calculated with multi-media fate models. Until now, unrealistic system settings were used for these calculations. The present paper outlines an improved model to calculate toxicity potentials: the global nested multi-media fate, exposure and effects model USES-LCA. It is based on the Uniform System for the Evaluation of Substances 2.0 (USES 2.0). USES-LCA was used to calculate for 181 substances toxicity potentials for the six impact categories freshwater aquatic ecotoxicity, marine aquatic ecotoxicity, freshwater sediment ecotoxicity, marine sediment ecotoxicity, terrestrial ecotoxicity and human toxicity, after initial emission to the compartments air, freshwater, seawater, industrial soil and agricultural soil, respectively. Differences of several orders of magnitude were found between the new toxicity potentials and those calculated previously.

Animals↗

PubMed2003

Evaluation of bioanalytical assays for toxicity assessment and mode of toxic action classification of reactive chemicals.

The toxicity of electrqphiles, including reactive organochlorines, epoxides, and compounds with an activated double bond was investigated. A set of different bioanalytical assays based on genetically modified Escherichia coli strains was set up to quantify cytotoxicity and specific reactivity toward the important biological nucleophiles DNA and glutathione (GSH). The significance of GSH for detoxification was assessed by cellular GSH depletion as well as by growth inhibition of a GSH-deficient strain. Tests for DNA damage comprised the measurement of induction of DNA repair systems, DNA fragmentation, and growth inhibition of a strain deficient in major DNA repair mechanisms. The most suitable assays for detection of mechanisms that underlie the observable cytotoxicity of the tested electrophiles were two sets of strains either lacking GSH or DNA repair in combination with their corresponding parent strains. Comparison of toxicity observed in those strains suggests three clearly distinguishable modes of toxic action for electrophilic chemicals: "DNA damage", "GSH depletion-related toxicity", and "unspecific reactivity". The class of chemicals causing DNA damage includes the epoxides 1,2-epoxybutane, (2,3-epoxypropyl)benzene, and styrene oxide. The class of chemicals with GSH depletion-related toxicity includes compounds with an activated double bond, like acrylates and acrolein. All reactive organochlorines and some epoxides were classified as unspecifically reactive because their toxicity is initiated by reactions with both biological nucleophiles. The work presented here is a contribution for an alternative hazard and effect assessment of organic pollutants based on mode of toxic action classification.

Biological Assay↗

PubMed2000

Acute toxicity test with Daphnia magna: an alternative to mammals in the prescreening of chemical toxicity?

In this study, the association between the acute toxicity of 15 compounds to Daphnia magna, expressed as 24- and 48-h LC(50) values, and the corresponding oral LD(50) values for the rat was tested. Since there was evidence of a strong relationship between the two species, the sample was extended to 54 cases by including the values for acute toxicity to D. magna and rat of more chemicals published by other authors. Thus, a total of 54 data points were further used to ascertain the relationship between the acute toxicity of chemical compounds to D. magna and that to the rat. To summarize its validity, the D. magna test is more specific than sensitive as an indicator of toxicity to the rat. When it is used with a chemical that has a high probability of being very toxic to D. magna (LC(50)< 0.22 mg/L), the test provides considerable information if it is positive, virtually giving evidence of toxicity to the rat (with a probability of 0.83). On the other hand, a negative test (D. magna LC(50)>0.22 mg/L) has a probability of correctly assigning nontoxicity to the rat equal to 0.74. This study and results published by other authors provide good evidence of the applicability of using invertebrate tests as prescreening methods, thus considerably reducing the number of mammals required in toxicity testing.

Animals↗

PubMed1995

Ricin toxicity and intracellular routing in tumoral HT-29 cells. I. Ricin routing and toxicity are related to the state of differentiation of HT-29 cells.

We previously showed that ricin, which is more cytotoxic to undifferentiated than to differentiated tumoral HT-29 cells, enters these cells by different routes. The final steps of ricin endocytosis were investigated in order to identify the translocation site from which ricin exerts its toxicity. Toxicity measurements and kinetic experiments followed by subcellular fractionation were run in parallel. In differentiated cells, from 20 min of internalization, radiolabeled ricin was found in a Golgi-enriched fraction. At 60 min, which corresponds to the lag time for ricin toxicity, the amount of radioactivity located in this fraction decreased without any concomitant increase in the other fractions. In undifferentiated cells, from 20 min of incubation, radiolabeled ricin was detected in the ER-enriched fractions. At 30 min, the lag time for ricin toxicity, the amount of radioactivity detected in these fractions decreased without any concomitant increase in the Golgi-enriched fraction. Monensin, which was used to confirm the passage of ricin through the Golgi, greatly increased ricin toxicity and diminished the lag time only in differentiated cells. Brefeldin A inhibited ricin toxicity when added before the end of the lag time in both cell populations and reduced the amount of ricin detected, respectively, in the Golgi- and ER-enriched fractions in differentiated and undifferentiated cells. We propose that ricin enters the cytosol from the Golgi apparatus and essentially from the ER in differentiated and undifferentiated HT-29 cells, respectively, and that these different intracellular routings might explain the differential toxicity of ricin.

Biological Transport↗

PubMed1984

Chemical models for toxic metabolites of bromobenzene derivatives. Relative toxicity toward isolated hepatocytes.

In the rat the hepatotoxicity of bromobenzene is greatly enhanced by the introduction of a cyano group adjacent to the bromine (i.e. o-bromobenzonitrile). Epoxide metabolites of these aryl halides are believed to be the actual toxic species, but epoxides of the latter compound also possess a second site of chemical reactivity not found in epoxides of bromobenzene, i.e. a Michael acceptor group formally related to acrylonitrile. Because these epoxides have never been isolated or synthesized for direct evaluation of their toxicity we have determined the toxicity toward isolated rat hepatocytes of a series of cyclohexene and cyclohexadiene derivatives containing epoxide and/or alpha, beta-unsaturated nitrile functional groups. Simple epoxides and unsaturated nitriles were much less toxic than bromobenzene itself, even if both groups were present in the same molecule. However, alpha, beta-unsaturated epoxides were found to be 2-3 times more toxic than bromobenzene, and at least 10 times more toxic than their saturated analogs, which is consistent with their relatively greater chemical reactivity. It is unlikely that Michael acceptor metabolites account for the increased toxicity of o-bromobenzonitrile relative to bromobenzene.

Alanine Transaminase↗

PubMed2005

Interaction of pH with mercuric chloride toxicity to penaeid prawns from a tropical estuary, East Coast of India: enhanced toxicity at low pH.

Toxicity tests were conducted to study the interaction of pH and the response of two size groups of penaeid prawns i.e. Penaeus monodon and Penaeus indicus to different sets of five concentrations of HgCl2 (0.01-0.09 mg l(-1)) under a broad range of pH conditions (5-9). Behavioural responses varied according to test solution concentration and nominated values of pH. Abnormality was detected in the higher concentrations with lower pH in smaller size group of P. monodon. High mortality was observed at higher concentration of test solution with low pH. Irrespective of species and size group LC50 demonstrated similar trend of variation with respect to time period. At pH 9 the threshold limit for 65-75 mm size group of P. monodon and P. indicus was 0.043 and 0.049 mg l(-1) respectively while it was 0.041 and 0.035 mg l(-1) respectively at pH 8; and 0.038 and 0.044 mg l(-1) respectively at pH 7. Relative toxicities were significantly varied except for bigger size groups in the studied pH ranges. The result was pronounced at pH 5 with maximum 1.61 times for inter-hour relative toxicity in contrast to all. At pH below 7 of mercury resulted more toxic compared to high pH range (>7) might be due to acid toxicity itself. At each pH smaller size groups were sensitive while bigger shown tolerant. P. monodon were more sensitive than P. indicus. The toxic order of pH effect was 9<8<7<6<5. Toxicity increased significantly (p>0.01) in acidic medium compared to alkaline.

Animals↗

PubMed1977

The effects of toxic and non-toxic serum phenytoin levels on carbohydrate tolerance and insulin levels.

The effect of toxic and non-toxic phenytoin levels on carobhydrate tolerance and insulin levels was studied in 18 patients with epilepsy and 17 control subjects. Toxic levels were defined as a serum level greater than 20 microgram/ml. Toxic levels occurred in 11 patients and nontoxic levels in seven patients. Blood glucose and insulin levels were measured at 30-min intervals for a period of 3 h following the ingestion of 50 g glucose. Blood glucose levels were measured by the ferricyanide method, and serum insulin levels by immunoassay of insulin with insulin antibody precipitate. Serum phenytoin levels were measured by gas liquid chromatography. The insulin profiles were the same for all three groups, but there was a significant delay in reaching peak glucose concentrations in patients with toxic levels of phenytoin. It was therefore confirmed that non-toxic levels of phenytoin do not affect carbohydrate tolerance or insulin levels when phenytoin is used in the routine treatement of epilepsy, and it has also been shown that toxic levels of phenytoin do not affect carbohydrate tolerance when the high levels are detected at an early stage.

Adolescent↗