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At least 73 records · Page 4Linked to original sources
PubMed1982

[The toxicological evaluation of styrene as an industrial chemical].

Recent development in toxicological study of styrene is summarized from the viewpoint of occupational health. The topics discussed are: 1) physico-chemical properties, 2) industrial use, work place environments and exposure control, 3) metabolism and biological monitoring of exposure, 4) general toxicity with special reference to dose-effect/response relationship in humans, and 5) in vitro and in vivo mutagenicity, mammalian teratogenicity and human/subhuman carcinogenicity. With 137 references.

Abnormalities, Drug-Induced↗
PubMed1983

The toxicologic evaluation of marcellomycin--an antineoplastic anthracycline antibiotic.

Dose-related toxicologic effects of marcellomycin, an antineoplastic anthracycline antibiotic, were observed in single-dose studies in mice iv (43.05-67.65 mg/m2) and dogs iv (41.0-90.2 mg/m2), and in multiple-dose studies in dogs iv (9.8-29.6 mg/m2 2X/week for 6 weeks) and rats sc (9 weekly doses at 26.2-72.2 mg/m2). Toxicity was primarily manifested by suppression of myeloid tissue, especially the erythrocytic and thrombocytic series, and lymphoid tissues. Initially a neutrophilic leukocytosis was observed in dogs and rats, which was considered possibly to be due to mobilization of the marginal and bone marrow neutrophil pools. In dogs, this was followed by a marked, dose-related neutropenia; and, in rats that died, there was marked depletion of bone marrow cells. Other toxicities observed included enteropathy, severe subcutaneous serofibrinous inflammatory edema and necrosis at injection sites, prostate and seminal vesicle atrophy, uterine hypoplasia, testicular and pancreatic degeneration, thyroid follicular proliferation and hemorrhage in various organs. In general, these toxicities were reversible in surviving animals during recovery periods. Significant cardiotoxicity was not demonstrated.

Animals↗
PubMed1997

Occupational risk and toxicology evaluations of industrial water conditioning.

This study addresses the chemical and toxicological questions due to the wide use of chemical treatment programmes for industrial cooling water. First, natural problems encountered in cooling tower systems were presented and grouped into three categories: (i) scaling; (ii) corrosion and (iii) biofouling. Chemical solutions adopted in industrial plants were outlined for each one in order to minimize damage and categorized as shut-down, production loss, heat transfer reduction, upsets, etc. Above all, the purpose of the work was to identify the most dangerous chemicals normally used, which means sources of chemical risk for safety workers and their environment; thus, symptoms of exposure, prevention measures and protection tools are also described.

Corrosion↗
PubMed1988

[Toxicologic evaluation of nitrates entering the body with plant products].

An acute toxicological experiment on rats has been performed. During 30 days the animals got nitrates with water and vegetable food. The activity of glucoso-6-phosphatase, malate dehydrogenase, beta-galactosidase, the content of N-acetylneuraminic acid was determined in liver, kidney and blood serum; the level of methemoglobin in blood was estimated. It was found that the changes of studied indexes are less expressed during nitrate introduction with food than with water; on the level of minimum concentrations the changes in non-specific symptom-complex were more expressed. The maximum innocuous intake of nitrates with vegetables is 500 mg in 24 hours taking into consideration the average weight of an individual (50 kg).

Animals↗
PubMed1995

Toxicologic evaluations of an immunotoxin, H65-RTA.

A series of acute and multiple dose toxicology studies were performed to support the clinical dose and to evaluate the systemic toxicity of an immunotoxin, H65-RTA. H65-RTA consists of a murine anti-CD5 monoclonal antibody and ricin A chain (RTA). The LD50 of H65-RTA was estimated to be between 60 and 62.5 mg/kg in the rat. H65-RTA was administered to the rat and the monkey as a bolus injection at doses of 0.1, 0.5, and 2 mg/kg and over 1-hr infusion at 0.2 and 2 mg/kg, respectively. Two to three weeks of postdosing recovery was included in the study design. Following repeated doses of H65-RTA, the following findings were demonstrated: peripheral edema, decreased body weight, decreased body temperature (monkey only) in addition to a general inflammatory reaction evidenced by changes in hematology, clinical chemistry, and urinalysis parameters. Histopathologically, chronic inflammation in the nonarticular soft tissue was found in the rat at doses of 0.1 mg/kg and higher and monkeys developed much more severe toxicity when compared to the rat at the same doses. Inflammation, hemorrhage, and/or edema were evident in a variety of tissues. Myeloid hyperplasia was also evident. Additional findings resulting from the drug-related stress involved adrenals, spleen, thymus, and lymph nodes. All toxicity was reversible. The antibody response was evident in rats at doses of 0.5 mg/kg and higher and in all monkeys at doses of 0.2 and 2 mg/kg. In conclusion, since H65 antibody does not cross-react with the T cells from either the rat or the cynomolgus monkey, the toxicity observed in the studies described above was not related to T lymphocytes and was probably due to a series of acute to subacute inflammatory reactions caused largely by the RTA moiety of H65-RTA.

Animals↗
PubMed1994

Preclinical toxicologic evaluation of DENSPM (N1,N11-diethylnorspermine) in rats and dogs.

A toxicology study of DENSPM was carried out in rats by multiple (once daily for 5 days) intravenous injection. Doses of 12.5, 25 and 50 mg DENSPM/kg were well tolerated. Infusion of 100 mg DENSPM resulted in distressing physical signs, including labored breathing, convulsive movements and acute death. There were no end-organ toxicities induced by this regimen as evaluated by serum chemistry and hematology examinations, and histopathologic exam of all major body organs. Transient hypotension was induced in rats and dogs by rapid infusion of DENSPM; the magnitude of this hypotension was decreased by slow infusion of DENSPM into dogs. Hypotension appears to be the dose-limiting toxicity of this agent when infused rapidly.

Animals↗
PubMed2004

Anti-arthritic effect and subacute toxicological evaluation of Baccharis genistelloides aqueous extract.

This work studies the potential subacute toxicological effects of the aqueous extract of Baccharis genistelloides (AEBg) and demonstrates a new anti-arthritic therapeutic effect. The treatment of the collagen-induced arthritis (CIA) group with 4.2 mg/kg AEBg induced an important decrease (75%) in CIA severity in all animals, while the 42 mg/kg dose treated only 50% of animals. After AEBg treatment, no significant differences were observed in body weight, aspect, color and relative weight of liver, kidneys, thymus or lungs between CIA groups. CIA and healthy AEBg groups treated with both doses did not show genotoxic effects to liver and kidney cells by the Comet assay, compared to its own control group. The augmented AST in the CIA group, compared to healthy control one was regularized by the AEBg treatment with 4.2 mg/kg but not with 42 mg/kg. No other significant difference was found on serum biochemical parameters, as well as on spontaneous or stimulated lymphocyte proliferation between CIA groups. The treatment of healthy animals with AEBg 4.2 mg/kg did not change the aspect, color or relative weight of kidneys, liver or lungs but reduced the body weight, the thymus and popliteal lymph node (PLN) relative weight and serum glucose and triglyceride levels. Concluding, our results indicate an anti-arthritic effects of AEBg without liver and kidney subacute toxicity and hypoglycemic and hypotriglyceridemic actions on healthy animals.

Administration, Oral↗
PubMed1998

Toxicological evaluation and risk assessment of chemical mixtures.

A major objective of combination toxicology is to establish whether a mixture of chemicals will result in an effect similar to that expected on the basis of additivity. This requires understanding of the basic concepts of the combined toxicological action of the compounds of the mixture: simple similar action (dose addition), simple dissimilar action (effect or response addition), and interaction (synergism, potentiation, antagonism). The number of possible combinations of chemicals is innumerable, and in vivo testing of these mixtures is unattainable from an ethical, economical, or pragmatic perspective. Prediction of the effect of a mixture based on the knowledge of each of the constituents requires detailed information on the composition of the mixture, exposure level, mechanism of action, and receptor of the individual compounds. Often, such information is not or is only partially available and additional studies are needed. Research strategies and methods to assess joint action or interaction of chemicals in mixtures such as whole mixture testing, physiologically based toxicokinetic modeling and isobologram and dose response surface analyses are discussed. Guidance is given for risk assessment of both simple and complex mixtures. We hypothesize that, as a rule, exposure to mixtures of chemicals at (low) non-toxic doses of the individual constituents is of no health concern. To verify the hypothesis is a challenge; to timely detect exceptions to the rule is the real challenge of major practical importance.

Animals↗
PubMed1983

Toxicological evaluation of the Columbia spacecraft.

Atmospheric contamination of spacecraft cabins has been a toxicological concern since this country began its efforts in manned space flight (1). Procedures have been developed and utilized for determining the identities and quantities of contaminant gases present in the cabin. Methods have also been developed for assessing and controlling the trace gas contaminant buildup within the closed cabins. Although more than 100 contaminant gases have been detected in the Shuttle cabin, for the most part the concentrations of these gases have been maintained below a toxicity hazard level.

Air Pollutants↗
PubMed2002

Evaluating toxicologic end points to derive minimal risk levels for hazardous substances.

The Agency for Toxic Substances and Disease Registry (ATSDR) uses chemical-specific minimal risk levels (MRLs) to assist in evaluating public health risks associated with exposure to hazardous substances. MRLs are estimates of daily human exposure to a chemical that are likely to be without an appreciable risk of adverse noncancer health effects over a specified duration of exposure. MRLs serve as screening levels for health assessors to identify contaminants and potential health effects that may be of concern for populations living near hazardous waste sites and chemical releases. MRLs are derived from toxicologic data complied from a comprehensive literature search and are presented in ATSDR's toxicological profile for that substance. They are based on the most sensitive substance-induced end point considered to be of relevance to humans. MRLs for each substance are derived for acute (1-14 days), intermediate (15-364 days), and chronic (365 days and longer) exposure durations, and for the oral and inhalation routes of exposure. In this paper, we present an overview of the approach used for evaluating the toxicologic end points in deriving the MRLs. Examples are given to illustrate the agency's efforts to achieve increased understanding, reduced uncertainty and improved public health guidance.

Administration, Oral↗
PubMed2006

In vitro toxicological evaluation of a dinuclear platinum(II) complex with acetate ligands.

In the present study the toxicological potential of a tumor-inhibiting dinuclear platinum(II) complex (bis(acetato)diammine-bis-micro-acetato diplatinum(II) dihydrate (BAP)) was evaluated, utilizing in vitro models of nephrotoxicity, myelosuppression and neurotoxicity. Regarding the discrepancies between the hallmark toxicity of the clinically utilized platinum drugs, we used three distinct referent compounds as follows cisplatin for the assessment of in vitro nephrotoxicity, carboplatin in case of cultured bone marrow cells and oxaliplatin for the determination of the in vitro neurotoxicty, respectively. The results obtained indicate that the investigated dinuclear complex is endowed by a lower potential to induce detrimental effects upon these typically susceptible platinum toxicity cellular populations as compared to the corresponding referent drugs. These findings, together with the previously encountered profound cytotoxic efficiency of this dinuclear platinum(II) complex against human tumor cell lines, recall for a further detailed evaluation of BAP as potential antineoplastic agent.

Animals↗
PubMed2001

Chemical composition, nutritive value, and toxicology evaluation of Mexican wild lupins.

The nutrient composition, toxic factors content, and nutritional and toxicological value of Lupinus splendens, L. rotundiflorus, L. elegans, L. simulans, L. exaltatus, L. reflexus, and L. madrensis species from Mexico were analyzed. The seeds of these species were a good source of protein. All the species showed a high lysine and tryptophan content, though sulfur amino acids were limiting. Cyanogenic glycosides were absent, and lectins, trypsin inhibitors, and tannins were present in low concentrations. Lupanine was the major alkaloid in almost all the samples, although sparteine was the major alkaloid in Lupinus reflexus (26.63 mg/g of sample). Cytisine was not found in any of the studied lupins. L. reflexus showed the highest acute toxicity, and L. elegans exhibited no toxicity as evaluated using a mice model. The alkaloid was reduced by hot-water extraction. The protein efficiency ratio in water-debittered seeds was relatively poor (1.1-1.5). These results suggest that the wild lupins studied represent a potential protein supply, and they could be domesticated and used for animal feed if the alkaloids were eliminated and the protein was supplemented with methionine, or if the lupins were used in mixture with cereals.

Evaluation Studies as Topic↗
PubMed1995

[Toxicologic evaluation of supermethrin, a pyrethroid insecticide, in rabbits and pheasants].

Basic information about a toxicologic hazard of the pyrethroid supermethrin (Research Institute of Chemical Technology, Bratislava) is presented in this paper for the conditions of acute intoxication in rabbits and pheasants and in the conditions of subacute intoxication in pheasants. The insecticide supermethrin under observation contains a cyanide groups in its molecule and can be included in the group of type II pyrethroids comprising among other substances also cypermethrin. Supermethrin is an analog of the latter and it has a different proportion of cis- and trans-isomers. At acute intoxication, supermethrin was applied to adult rabbits at doses of 2,000; 3,000; 4,000; 5,000 and 6,000 mg/kg and to adult pheasants at doses of 2,000; 4,000; 5,000 and 6,000 mg/kg live weight. Supermethrin dissolved in sunflower oil at a 1:2 ratio was administered in the above differentiated doses at single application by a peroral tube. Not even the highest supermethrin dose (6,000 mg/kg live weight) caused any clinical signs of intoxication in the birds. This fact suggests that its LD50 for rabbits and pheasants will apparently exceed the value of 6,000 mg/kg l.w. At subacute intoxication, supermethrin was applied as dissolved in sunflower oil (at a 1:2 ratio) by per os tube at a dose of 500 mg/kg l.w. once a day within five days. The subacute doses of supermethrin did not induce, besides mild diarrhea at the end of the trial, any other clinical signs of intoxication in the pheasants. The negative effect of supermethrin (even though negligible) on the digestive tract of pheasants is in agreement with the results determined in sheep in the conditions of subchronic intoxication (Neuschl et al., 1995), Supermethrin administration in sheep resulted in permanent and intensive diarrheas. These findings clearly indicate that supermethrin administered at lower doses primarily affects the function of digestive tract. Tab. 1 shows the effect of supermethrin on the live weight of pheasants in the conditions of subacute intoxication. The negligible decrease in live weight recorded at the end of the trial was not due to supermethrin effects. It was also recorded in the control group. There were no significant differences between the control and experimental group. It was probably induced by the stress resulting from daily applications of the tested substance. In case the guidelines for its areal application (140 g/ha) are observed, it will not be toxic for rabbits and pheasants nor probably for hares and/or other gallinaceous birds. Supermethrin seems to be a little toxic substance according to WHO (1975) classification.

Animals↗
PubMed1995

Guideline limit volumes for dosing animals in the preclinical stage of safety evaluation. Toxicology Subcommittee of the Association of the British Pharmaceutical Industry.

Guideline limit volumes for dosing laboratory animals by oral and parenteral routes in the preclinical stage of safety evaluation were agreed following discussions by the Toxicology Subcommittee of the Association of the British Pharmaceutical Industry. The guideline values represent common practice rather than absolute maxima. Whilst the guideline values are expected to be of value to scientists and technical staff involved in study design and applicable to the majority of routine safety evaluation studies, scope remains to make the case for special investigations. The need to carefully consider animal welfare and physiology, current legislation, the use of appropriate dosing technology and formulations, and other practical aspects of study conduct, is emphasised.

Administration, Oral↗
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↗
PubMedDate not supplied

[Toxicologic evaluation of the space shuttle "Columbia"].

Atmospheric contamination of spacecraft crew cabins has been a toxicological concern since this country began its efforts in manned space flight (1). Procedures have been developed and utilized for determining the identities and quantities of contaminant gases present in the crew cabin environment. Methods have also been developed for assessing and controlling the trace gas contaminant buildup within the closed environment of spacecraft cabins. Although nearly one hundred contaminant gases have been detected in the Shuttle crew cabin, for the most part, the concentrations of these gases have been maintained below a toxicity hazard level.

Air Pollutants↗