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At least 19 recordsLinked to original sources
PubMed1992

Comparative toxicity of four chlorinated dibenzo-p-dioxins (CDDs) and their mixture. Part I: Acute toxicity and toxic equivalency factors (TEFs).

There is presently no scientifically proven method to assess the toxicity of environmental samples containing complex mixtures of chlorinated dibenzo-p-dioxins (CDDs) of known composition. Their risk assessment is currently based on the interim concept of toxicity equivalency factors (TEFs), with the unproven assumption that all interactions of CDDs are additive. To address this problem we conducted acute toxicity studies with four different CDDs, viz 2,3,7,8-tetrachlorodibenzo-p-dioxin (tetra-CDD), 1,2,3,7,8-pentachlorodibenzo-p-dioxin (penta-CDD), 1,2,3,4,7,8-hexachlorodibenzo-p-dioxin (hexa-CDD) and 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (hepta-CDD), all containing chlorine substituents in the crucial 2,3,7,8-positions. The homologues, dissolved in corn oil/acetone, were administered to groups of five male Sprague Dawley rats at several doses (at least three) by gastric intubation. The obtained mortality data were employed to calculate the LD20,50 and 80 for each homologue. These data were subsequently used to prepare equipotent doses (expected mortality of 20, 50 and 80%) of a mixture containing all four homologues, each of them contributing one fourth of the toxicity, under the assumption of additive toxicity. The obtained LD50 value and (TEF) was for tetra-CDD 43 micrograms/kg (1), penta-CDD 206 micrograms/kg (0.2) hexa-CDD 887 micrograms/kg (0.05) and hepta-CDD 6325 micrograms/kg (0.007), respectively. The dose-response to the mixture confirmed the hypothesis of strict additivity in the acute toxicity of the four CDD homologues.

Animals↗
PubMed1978

[Mechanism of methamphetamine toxicity in grouped mice and the effects of centrally acting drugs on its toxicity (author's transl)].

The mortality of ddK mice treated with 40 mg/kg i.p. of methamphetamine (MA) was 85% in grouped conditions (10 mice in a cage) and 3% in individually isolated conditions. This mortality was not altered by the social environments even when other mice in the cage were not treated with MA. The mortality of mice individually isolated in cages with transparent walls was significantly higher than that of completely isolated mice. Almost all neuroleptics dose-dependently antagonized the MA toxicity in grouped mice, in small doses. The antagonizing activity of clozapine was somewhat weak, and sulpiride potentiated MA toxicity. Phentolamine and propranolol antagonized the MA toxicity at higher doses than neuroleptics. Reserpine and tetrabenazine previously given to mice remarkably antagonized the MA toxicity. H44/68 (a tyrosine hydroxylase inhibitor) had a considerable effect in antagonizing the MA toxicity, but diethyldithiocarbamate, U-14, 624 and FLA 63 (dopamine-beta-hydroxylase inhibitors) prevented the MA toxicity to a lesser extent than did H44/68. Apomorphine had no effect on the MA toxicity. The present data show that the MA toxicity in grouped mice (the increase in mortality) was enhanced by the presence of other mice, and suggest that the norepinephrine neurons play an important role in promoting the MA toxicity. Neuroleptics antagonize MA toxicity probably by blocking alpha-receptors in the central nervous system.

Adrenergic alpha-Antagonists↗
PubMed1992

Criteria for judging the relative toxicity of chemicals from developmental toxicity data: a workshop summary.

In summary, participants of this workshop confirmed that many criteria need to be considered when interpreting the results of developmental toxicity studies. All aspects of developmental toxicity are of interest, but their importance to the consideration varies along the continuum from hazard detection to risk estimation. As with many other manifestations of toxicity, potential developmental risk to humans is a function of exposure and developmental toxicity, the latter reflecting the inherent potential of a substance to cause an adverse effect under some defined condition. All of the criteria discussed in this workshop were considered to be of some importance in characterizing the developmental toxicity of a substance, their relative importance being a function of the question under consideration. Proper interpretation of developmental toxicity data, which must include prenatal as well as postnatal observations to be considered complete, should take into account the differential toxicity to the mother and the conceptus, the nature of the developmental toxicity observed, and the consistency of response between species. The proximity of human exposure levels to dose levels that are developmentally toxic in animals is a major determinant of the potential for hazard to humans. Mechanistic and pharmacokinetic knowledge can modulate interpretation of descriptive data and refine the prediction of human hazard. Recognizing that in vitro studies will never completely recapitulate the results of in vivo studies, the committee to update the "Smith list" will move forward taking the discussions of this workshop into account.

Animals↗
PubMed1992

The evolution of toxic effluents in fires and the assessment of toxic hazard.

Toxic hazard in fire depends upon three factors: the fire growth curve (mass loss rate of materials, kg/min) and volume dispersal (kg/m3), the yields of toxic products (e.g. kg CO/kg fuel burned) and the toxic potency of the products (exposure dose needed to cause toxic effects, e.g. lethal dose of CO in ppm.min). The first and second sets of data are obtainable from large-scale tests or small-scale tests and mathematical modelling, the third and some information on the second are derived from toxicity studies of combustion products in small-scale tests or of individual fire gases. Small-scale toxicity test data on materials expressed as lethal mass loss exposure doses (LCt50 g min m-3) can be used in Fractional Effective Dose (FED) hazard assessments, providing the decomposition conditions of the test reproduce those in the fire being examined; principally either non-flaming oxidative, early well-ventilated flaming, or vitiated post-flashover. Although bioassays are needed for a full toxicity assessment, it is now possible to predict the toxic potency of materials to some extent from analytical data alone. The suitability of the small-scale test decomposition conditions are determined in terms of non-flaming or flaming behaviour, temperature (or radiant flux), CO2/CO ratio and oxygen concentration. Existing small-scale test methods provide reasonable models for materials under non-flaming oxidative and early flaming conditions, although the data base for the latter is poor. Only the DIN 53436 method is able to model vitiated post-flashover decomposition conditions, but data for this condition are almost non-existent.

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↗
PubMed1992

Strategies for the identification of non-polar toxicants in aqueous environmental samples using toxicity-based fractionation and gas chromatography-mass spectrometry.

Toxicity-based fractionation is a useful tool for the isolation and identification of non-polar organic compounds that are present at toxic concentrations in aqueous environmental samples. Methods for isolating such toxicants from the aqueous sample matrix and techniques for fractionating the compounds for the purpose of reducing the complexity of the sample matrix and thus facilitating identification are evaluated. Strategies for analyzing gas chromatographic-mass spectrometric data and confirming toxicant identification are presented. Studies that use toxicity-based fractionation for identifying the cause of toxicity in aqueous environmental samples such as municipal and industrial wastewater treatment plant effluents and ambient waters are discussed.

Chemical Fractionation↗
PubMed1975

[Investigations on toxic fractions of swine erysipelas bacteria (erysipelothrix rhusiopathiae). 1. Communication: Toxicity investigation on a phenol water extract in chicken embryos (author's transl)].

The watersoluble fractions (WESTPHAL et al., 1952 a, b) of twelve Erysipelothrix rhusiopathiae strains, which differed in virulence were tested for toxicity for ten day old chick-embryos by the route of i.v. injection. The LD50-values ranged from 108 mug to 0.01 mug toxin dry weight/embryo. The different toxicity of these extracts for chick-embryos was compared with the virulence of the corresponding strains in swine: The extracts of four strains with high virulence were very toxic for chick-embryos (LD50:0,01 mug to 0.207 mug) The extracts of four non-virulent strains were low-, respectively non-toxic (LD50:10.95 mug to 108 mug) The extract of one virulent strain showed an intermediate degree of toxicity (LD50:2.8 mug) In tese nine strains there was a correlation between virulence for swine and the toxicity of the extracts for chick-embryos. But this relation could not be found for three other strains.

Animals↗
PubMed1992

Role of maternal toxicity in assessing developmental toxicity in animals: a discussion.

The belief that any drug or chemical, when administered at a high enough dose, can be expected to produce fetal malformations is not consistent with the facts. However, the stress associated with maternally toxic doses can be expected to result in associated, often transient, fetal abnormalities that may not be the result of deviant organogenesis. Sometimes the toxicity toward the pregnant animal, including her embryos/fetuses since they are hardly in a sanctuary, is severe enough to result in resorption of the embryo or abortion of the fetus. Thus, it is possible that the embryolethality and other indications of developmental toxicity, produced by some drugs and chemicals, may be the result of a mechanism(s) other than selective toxicity toward the embryo. Also, some test materials have been shown to affect maternal homeostasis, thereby disrupting support to the embryo, without causing significant overt toxicity to the embryo or dam; e.g., the endocrine system of the dam is altered. Routine testing has thus far revealed a relatively limited number of true teratogens, although a large number of drugs and chemicals have resulted in fetal effects such as developmental variations when administered at doses that approach lethal levels. Such effects on the fetus should be expected when the maternal animals are stressed by the high dosages usually employed. A better understanding of the etiology and biological relevance of the embryo/fetal deviations often seen in developmental toxicology studies might help to avoid the sometimes unjustified withholding of potentially useful drugs and chemicals from the marketplace.

Abnormalities, Drug-Induced↗
PubMed1978

A study on the toxicity of natural food dyes--toxicity and enzyme inhibition in Paramecium caudatum.

The toxicity of 14 commercial natural dyes which are widely used as food additives in Japan was studied on Paramecium caudatum. Laccaic acid and capsanthin were found to be very toxic to Paramecium caudatum. Some of the commercially available carminic acid and crocin were also toxic. The inhibitory effect of natural food dyes on leucine aminopeptidase, acid phosphatase and esterase in vitro was proportional to the toxic effect of the dyes on the survival time of Paramecium caudatum. Analyses of the commercial natural food dyes by high performance liquid chromatography failed to identify the toxic components.

Acid Phosphatase↗
PubMed1979

Studies on the toxicity of coal-tar dyes. I. Photodecomposed products of four xanthene dyes and their acute toxicity to fish.

The acute toxicity of photodecomposed products of Erythrosine, Eosine, Phloxine and Rose Bengale were studied, since it was found that toxicity of these dyes to fish increased after the dyes had been photoirradiated. Photodecomposed products of the dyes were isolated and identified with UV, IR, NMR spectra and the acute toxicity of those compounds were determined by TLm test. As results of these studies, it became clear that the toxicity of photodecomposed organic products (dehalogenated compounds of dyes) were lower than the mother compounds. The increases in toxicity of the xanthene dyes by photo-irradiation were attributed to the liberated halogens by irradiation.

Animals↗
PubMed1979

Bismuth toxicity in man II. Review of bismuth blood and urine levels in patients after administration of therapeutic bismuth formulations in relation to the problem of bismuth toxicity in man.

A survey of the leterature on bismuth toxicity in man in relation to blood level data, has revealed the necessity of distinguishing between lipid soluble and water soluble organic complexes of bismuth on the one hand and the simple inorganic salts of bismuth on the other hand. A characteristic feature of the former, illustrated by the water soluble bismuth complex triglycollamate, is the high bismuth levels (due to absorption of the complex as such) and the nephrotoxic properties of the compound in man. Bismuth absorption after administration of the simple inorganic salts of bismuth is postulated to occur in the form of ionic bismuth as such, low bismuth levels being characteristic features of such compounds. Bismuth blood and urine levels obtained from patients after administration of a new anti-ulcer drug (Bicitropeptide) in a well controlled clinical trial are discussed and suggest that that this bismuth containing drug behaves pharmacologically in a manner similar to the inorganic bismuth salts in man, low bismuth blood levels and the absence of toxic side effects being conspicuous features of the drug. Based on these considerations, it is proposed that the pharmacologically active bismuth compounds be divided into four different groups depending on structure, stability and solubility. The question as to what constitutes a "toxic bismuth blood level" can only be discussed in relation to the new proposed sub-division of bismuth compounds and is only meaningful if the term is defined to relate only to ionic bismuth (presumably bound to a large extent to blood proteins). Based on information gleaned from the literature and blood level values reported in the clinical trial referred to, it is suggested that bismuth blood level values below 50 micrograms/ml are highly unlikely to be associated with meaningful toxicity in man. Finally, attention is drawn to the reversibility of bismuth toxicity in man as reported by many authors irrespective of the type of bismuth compound concerned.

Animals↗
PubMed1979

Serum thyroglobulin in patients with toxic and non-toxic goitres compared to sex- and age-matched control subjects.

To study serum thyroglobulin (Tg) levels in patients with thyroid disorders compared to sex- and age-matched control subjects and to correlate the Tg levels to the thyroid function, 71 patients were investigated before treatment was started. Serum Tg, measured by a double antibody radioimmunoassay, was elevated in all groups with thyroid disorders, as compared to their controls, but the values showed large overlaps between groups. The highest median values were seen in the two groups of patients with toxic goitres (toxic adenoma and Graves' disease). The Tg values in patients with non-toxic goitres (diffuse and nodular) and in controls showed a log normal distribution, whereas the distribution of values from patients with toxic goitres was different. No correlation was found between serum Tg and serum thyroxine, serum triiodothyronine and serum TSH, respectively. It is concluded that determination of serum Tg is of little diagnostic value in thyroid diseases.

Adenoma↗
PubMed1992

Toxicity studies of a synthetic antioxidant, 2,2'-methylenebis (4-ethyl-6-tert-butylphenol) in rats. 1. Acute and subchronic toxicity.

The acute and subchronic toxicity studies on 2,2'-methylenebis (4-ethyl-6-tert-butylphenol) (MBEBP) were conducted using male and female Wistar rats. In acute toxicity test, the LD50 values were estimated to be greater than 10 g/kg BW by oral and intraperitoneal administration in each sex. In subchronic toxicity test, groups of 10 rats of each sex were fed a diet containing 0.2, 1.0 or 5.0% of MBEBP and examined at 4 and 12 weeks. Body weight gain was significantly depressed at doses of 1.0 and 5.0% in both sexes, but the depression in the 1.0% group was severer than that in the 5.0% group in males. Hematological analysis showed slight but significant decrease of hemoglobin in the 1.0 and 5.0% groups of both sexes. Urine analysis showed no remarkable changes in all treated rats of both sexes. In biochemical analysis of serum, decrease of triglyceride level and cholinesterase activity, and increase of amylase activity were observed in treated rats. Histopathologically, testicular atrophy and decrease of spermatogenesis were observed in male rats fed 1.0 or 5.0% MBEBP for 4 and 12 weeks and vacuolization of parathyroid gland cells was observed in female rats fed 1.0 and 5.0% MBEBP for 12 weeks. In subchronic test, the lowest observable adverse effect levels for MBEBP toxicity were estimated to be 171 mg/kg BW/day in male rats and 180 mg/kg BW/day in female rats.

Administration, Oral↗
PubMed1975

[On the toxicity of CT-1341 evoked by long-term administration. II. Subacute and chronic toxicities of alphaxalone in rats (author's transl)].

Alphaxalone, an anesthetic steroid dissolved in 20% Cremophor solution was administered intraperitoneally to test the subacute toxicity (administration for one month) and chronic toxicity (administration for 3 months). In daily doses less than 8 mg/kg, alphaxalone did not show any particular toxic sign after administered for three months. Rats tolerated to daily administration of 20 mg/kg for three months, without showing severe toxic signs in body weight curve, blood cells and biochemical data obtained in blood and urine. However, some female rats receiving 50 mg/kg/day of alphaxalone, died by paralysis of respiratory center at the second day. Main histo-pathological changes induced by subacute and chronic administrations of the larger doses than 20 mg/kg, were swelling of cells in the liver and kidneys, but severe pathological changes were not seen in any organs.

Alfaxalone Alfadolone Mixture↗
PubMed1976

Triterpenes of toxic and non-toxic taxa of Lantana camara.

The taxa of Lantana camara toxic to animals contain lantadene A lantadene B, whereas in two non-toxic taxa other triterpenes predominate. Several new triterpenes have been characterized. Contrary to earlier claims, lantadene A and to a lesser extent lantadene B are toxic when administered intraruminally to sheep.

Animal Feed↗
PubMed1992

Factors affecting the toxicity of dioxin-like toxicants: a molecular approach to risk assessment of dioxins.

The numerous toxic responses of dioxin-like compounds are mediated by the intracellular Ah (aryl hydrocarbon) receptor. It has been suggested that the regulation of dioxins and similar substances could be placed on a molecular foundation by considering the proportion of Ah-receptor sites occupied by toxicant molecules. The present work has shown that the following formation not yet available would be needed in order to develop this approach: correlation between dioxin exposure and human tissue levels; accurate determination of the association constants for human Ah-receptor with toxicant, and for human receptor-ligand complex with DNA; and knowledge of the intracellular concentrations of both receptor binding sites and DNA binding sites. Furthermore, since not all dioxin-like substances behave identically, this information would need to be gathered for a wide variety of substances.

Animals↗
PubMed1992

In vitro phototoxicity of nifedipine: sequential induction of toxic and non-toxic photoproducts with UVA radiation.

Anecdotal reports suggest that the dihydropyridine calcium antagonist, nifedipine (NIF), may be phototoxic in human skin. We have studied NIF phototoxicity in vitro using UVA fluorescent tubes (Sylvania PUVA). NIF was phototoxic to Candida albicans and induced photohaemolysis both with NIF present during irradiation and with pre-irradiated drug. In V79 hamster fibroblasts, NIF (10 micrograms ml-1) was phototoxic MTT assay) 24 h after irradiation (0-112 kJ m-2); at 7.5 kJ m-2, about 70% of cells were damaged whilst at 37.5 kJ m-2, only about 45% of cells were damaged. A similar pattern was seen with pre-irradiated NIF. Absorption spectroscopy showed that the NIF absorption maximum (Amax approximately 340 nm) blue-shifted to 314 nm at low UVA doses (7.5 kJ m-2 or less) and red-shifted to 345 nm at higher doses (isosbestic point, 325 nm). Thin layer chromatography of irradiated NIF showed a single photoproduct (PP1; Amax approximately 314 nm) formed at 7.5 kJ m-2 or less which disappeared at higher UVA doses to give further photoproducts. PP1 was highly dark toxic to V79 cells (50% damage at about 5 micrograms ml-1) but PP1 pre-irradiated with UVA was non-toxic. Preliminary gas chromatography-mass spectroscopy studies suggest that PP1 is the nitroso derivative of NIF. These results indicate that NIF phototoxicity in vitro is partially mediated by initial formation of a toxic photoproduct (PP1) but, paradoxically, subsequent UVA irradiation may reduce phototoxicity. The NIF concentrations required to induce in vitro phototoxicity are much greater than therapeutic plasma levels. Unless there is skin accumulation of NIF or PP1, our in vitro results suggest that NIF may not be an important skin-photosensitizing agent in vivo.

Animals↗