Toxicological Changes Research Articles

Toxicologic changes in rats fed graded dietary levels of ochratoxin A

In a short-term study, groups of weanling male rats were fed a semipurified diet containing 0, 2.4, 4.8, 9.6 or 24 ppm of ochratoxin A for a period of 2 weeks. Growth retardation and reduced food consumption were observed in rats fed 9.6 or 24 ppm but not in those fed 2.4 or 4.8 ppm of the compound. Rats fed 24 ppm of ochratoxin A had elevated serum blood urea nitrogen (BUN) values and significantly increased kidney weights accompanied by marked degenerative changes involving the entire tubular system. Similar, but less extensive, changes were noted in the 4.8 and 9.6 ppm groups. In a subacute study groups of 15 weanling male and female rats were fed a semipurified diet for 90 days containing 0, 0.2, 1.0 or 5.0 ppm of ochratoxin A. Body weight was significantly reduced in the 5.0 ppm group. In contrast to the short-term study, relative kidney weights were reduced in the 1.0 and 5.0 ppm groups, and the latter group had elevated BUN values. Dose-related pathologic changes were noted in the kidneys of all treated rats. In the 0.2 ppm group a few scattered cells in the proximal convoluted tubules underwent granular eosinophilic degeneration, and a few cells developed bizarre giant nuclei. At the higher doses, similar, but more extensive changes were observed.

Chronic toxicity of DMSO in primates

Oral administration or dermal application of pharmaceutical grade DMSO has been evaluated in rhesus monkeys ( Macaca mulatta) over an 18-month period. Daily doses of 1, 3, or 9 ml/kg body weight of a 90% ( v v ) aqueous DMSO solution were administered topically or intragastrically in equally divided portions each morning and afternoon. The topical applications covered the entire abdominal area. Control animals were given 9 ml/kg of water by either route. Body weight, blood pressure, heart rate, respiratory rate, body temperature, water consumption, neurologic reflexes, and ophthalmologic characteristics were observed. Electrocardiograms, hematologic studies, and chemical analyses of blood and urine also were done. Gross and histomorphologic examinations were made terminally. Frequent ophthalmoscopic and biomicroscopic examinations of these animals revealed no evidence of the ocular toxicity reported to have been observed in subprimate species. Animals given the highest oral dose of DMSO could not tolerate it and died between weeks 15 and 53 of the study. Histologically, atelectasis and emphysema were the only pathologic changes. Some regurgitation and/or tracheal inspiration of this highly volatile irritating substance might have occurred. No toxicologic or pathologic changes attributable to oral administration of 1 or 3 ml/kg or topical application of 1, 3, or 9 ml/kg of DMSO (90%) were found.

Importance of dietary Ca:PO4 ratios on skeletal, Ca, Mg, and PO4 metabolism.

ARTICLESImportance of dietary Ca:PO4 ratios on skeletal, Ca, Mg, and PO4 metabolismI ClarkI ClarkPublished Online:01 Sep 1969https://doi.org/10.1152/ajplegacy.1969.217.3.865MoreSectionsPDF (1 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByEffects of phosphorus and calcium to phosphorus consumption ratio on mineral metabolism and cardiometabolic healthThe Journal of Nutritional Biochemistry, Vol. 80Interaction Between Calcium and Phosphorus and the Relationship to Bone Health17 May 2017Requirement for digestible calcium by 25 to 50 kg pigs at different dietary concentrations of phosphorus as indicated by growth performance, bone ash concentration, and calcium and phosphorus balances1Journal of Animal Science, Vol. 94, No. 12Digestibility of calcium in feed ingredients and requirements of digestible calcium for growing pigsAnimal Production Science, Vol. 56, No. 8The site of net absorption of Ca from the intestinal tract of growing pigs and effect of phytic acid, Ca level and Ca source on Ca digestibility20 March 2014 | Archives of Animal Nutrition, Vol. 68, No. 2Determination of endogenous intestinal losses of calcium and true total tract digestibility of calcium in canola meal fed to growing pigs1Journal of Animal Science, Vol. 91, No. 10The role of water quality in large mammal migratory behaviour in the Serengeti6 June 2012 | Ecohydrology, Vol. 6, No. 3Bone consequences of high dietary phosphateClinical Imaging, Vol. 34, No. 6Cartilage and Bone as Target Tissues for Toxic Materials15 December 2009Nutritional Determinants of Bone HealthJournal of Nutrition For the Elderly, Vol. 27, No. 1-2Effects of Prolonged High Phosphorus Diet on Phosphorus and Calcium Balance in RatsJournal of Clinical Biochemistry and Nutrition, Vol. 40, No. 3Neonatal Calcium, Phosphorus, and Magnesium HomeostasisPlasma and urine electrolyte and mineral concentrations in Thoroughbred horses with recurrent exertional rhabdomyolysis after consumption of diets varying in cation-anion balanceAmerican Journal of Veterinary Research, Vol. 63, No. 7Controversy over Dietary PhosphorusJournal of the American College of Nutrition, Vol. 20, No. 4The Institute of Medicine’s “Dietary Reference Intake” for Phosphorus: A Critical PerspectiveJournal of the American College of Nutrition, Vol. 20, No. 4HypophosphataemiaPathophysiology, effects and management on the intensive care unit13 May 2002 | Anaesthesia, Vol. 53, No. 9Changing Phosphorus Content of the U.S. Diet: Potential for Adverse Effects on BoneThe Journal of Nutrition, Vol. 126Physiological and Toxicological Changes in the Skin Resulting from the Action and Interaction of Metal Ions25 September 2008 | Critical Reviews in Toxicology, Vol. 25, No. 5The Effects of High Phosphorus Intake on Calcium HomeostasisDietary Phosphorus, Calcium Metabolism and Bone ,The Journal of Nutrition, Vol. 123, No. 9The hemodynamic effect of dietary calcium supplementation on rat renovascular hypertensionBasic Research in Cardiology, Vol. 88, No. 1The Role of Nutrition in the Functioning of Skeletal Tissue27 April 2009 | Nutrition Reviews, Vol. 50, No. 12The effect of habitat geology on calcium intake and calcium status of wild rodentsOecologia, Vol. 88, No. 4Skeletal SystemMagnesium Absorption: Mechanisms and the Influence of Vitamin D, Calcium and PhosphateThe Journal of Nutrition, Vol. 121, No. 1Comparison of chemical, histomorphometric, and absorptiometric analyses of bones of growing rats subjected to dietary calcium stress.Journal of the American College of Nutrition, Vol. 9, No. 6Effect of Dietary Calcium on In Vitro Aortic Tissue Responsiveness to a Hypertensive Factor3 July 2009 | Clinical and Experimental Hypertension. 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ノルマルヘキサンの末梢神経毒性に関する電気生理学的研究

n-Hexane (hexyl hydride, caproyl hydride) is an ingredient of petroleum, and volatile. It is widely used as a safe solvent in the industrial fields. Rcently 17 cases of peripheral neuropathy caused by industrial use of n-Hexane have been reported in Japan. In these cases, n-Hexane vapour concentrations in the work rooms were 500 to 1, 000 p.p.m. and local concentrations near the sources were 1, 000 to 2, 000 p.p.m.. The aim of this experiment was to study the neurotoxicity of n-Hexane through animal experiments, and to confirm the critical level of the vapour concentration of n-Hexane which just causes these pathological states. The animals used in this experiment were SMA strain male mice, and were separated into 6 groups of 10 mice each. Each gorup of animals was housed in a gas-chamber. These groups were kept in n-Hexane vapour for 24 hours a day, 6 days a week, and for one year. The vapour concentrations of n-Hexane in these chambers were as follows; (the values outside the parenthesis indicate the planned concentrations and those inside indicate the mean vapour concentrations which were measured throughout the total experiment period of one year.) group 1:100 (98.6) p.p.m., group 2:250 (272.0) p.p.m., group 3:500 (551.9) p.p.m., group 4:1, 000 (1030.1) p.p.m., group 5:2, 000 (1903.6) p.p.m., and group 6: the control. The examinations were made on the distal part of the lower extremities of the animals. The examinations used were electromyography, stregthdurations curves, electrical reaction time, and flexor / extensor chronaxy ratio. Other investigations performed were that on gait posture and measurement of the grade of muscle atrophy of the lower extremities. Histological examinations of the distal muscles of the lower extremities were performed in some of the animals. The results of these examinations were as follows; 1) Electromyography: Complex N.M.U. voltages were observed frequently in NO. 3, 4, and NO. 5 groups and less frequently in NO.2 groups. Fibrillation voltages were observed in NO. 4 and NO 5 groups. Low voltages were rarely observed. 2) Strength-duration curves: in most of the animals of NO.4 and NO.5 groups the curves showed type. The curves showed mixed denervation (incomplete denervation) types in most of the animals of NO. 2 and 3 groups an in some of the NO. 4 group. 3) Electrical reaction time: it was clearly longer in NO. 4 and 5 groups. 4) Flexor/extensor chronaxy ratio: it was significantly lower than 1.0 in NO. 4 and 5 groups, while it was near 2.0 in the control group. 5) Gait posture: in NO.4 and 5 groups animals showed abnormal gait posture which might be understood as the result of muscle weakness caused by n-Hexane. 6) Muscle atrophy: decreased muscle volumes of the lower extremities were seen more or less than in the animals of NO.4 and 5 groups. 7) Histological examinations: histological specimens of distal muscles of the lower extremities of NO.5 group animals showed neural muscular atrophy. The diagnosis was made in each animal according to the results of these examinations. The results of the examinations mentioned above might lead to a conclusion that peripheral nerve disorders of the animals were brought about through one year exposure of n-Hexane and that the effective toxic concentration of n-Hexane was 250 p.p.m. or more. Far more study might be necessary to discuss about the effects of n-Hexane on the central nervous system including the spinal cord. In view of the fact that man is several times more sensitive concerning the toxicological nervous changes than the mice, which were used in these experimental studies, the results of this sutdy might lead to the conclusion that the vapour concentration of n-Hexane in the work room should be 100 p.p.m. or less. The electrophysiological examinations mentioned above might be interesting methods to investigate the biological effects of industrial organic solvents.

EXPERIMENTAL STUDIES ON THE TOXICITY OF BENZENE HEXACHLORIDE (BHC) AND DICHLORODIPHENYLTRICHLOROETHANE (DDT)

Summarizing the above mentioned experimental results, in the inhalation group of BHC powder, the rats showed symptoms of temporary excitability, eye hemorrhage and excess secretion of nasal mucous. Except a youngest and smallest of the 6 rats which died of convulsions, the remaining 5 rats survived and were not poisoned.The symptoms of mice were the same toxic symptoms accompanying each administration as was described in the first report. Slight tremors were observed and remarkable convulsions caused the younger ones to die early.In the DDT group, the symptoms of the mice showed the same results as the foregoing administrations. Severe tremors appeared and at last death resulted with convulsions.According to these results, it was shown that the inhalation of BHC and DDT powder was toxic to laboratory animals.Concerning the dust inhalation tests, the first problem is to be undeniable about the injurious effects of the inhaled powder dust itself.On the effects of powder or dust for living bodies are reported too many to enumerate, but in short they are: (1) intoxications or allergic diseases, (2) mucous diseases, (3) pulmonary diseases, (4) dissemination of infectious diseases and (5) der-matological diseases.The conditions which control the noxiousness of the dust are: (1) the size of the dust particles, (2) number, (3) hardness, (4) shape, (5) solubility, (6) electric chargeabilty, (7) deep-reaching action, and (8) chemical reaction and ingredient. Under these conditions the influences to living body varies greatly in degree.The atmospheric dusts enter into the body through the nose, mouth and throat. However, the skin and the mucous membrane are also concerned with that.When the dusts are inhaled, by the filtering function or self protective function of the body the dusts are discharged out of the body. When the bodies are forced to inhale an excessive quantity of dust, these self-protective functions gradually decline and the influence of the dust increases.Thus the results are that when the powder is inhaled into the lungs the soluble particles are dissolved into the humours of the surface of the alveoles and insoluble ones are stuck on the surface or are caught by the cells and entered into the organs, stimulated them, and caused inflammations and other changes.According to the author's experiments, in the inhalion test of BHC and DDT powder, remarkable specific toxic symptoms of BHC and DDT were caused by the inhalation and the changes were confirmed histopathologically. That is, the changes of the lung due to the inhalation of both powders were alveolar pneumonia and catarrhal pneumonia, in addition to emphysema, atelektasis, and hemorrhage.The effects of various dusts upon the lung and its histologic.al findings are agreed to by many research workers in the past. The changes of the lung in this test and the effects of the dust itself are not denied.As to the histological findings about the effects upon other organs than the lungs, both BHC and DDT powder showed toxicological changes in the liver and the spleen. Thus it is understood that these changes are not caused by the dusts alone. Each constituent of BHC and DDT, the organic compounds contained in the dust, are absorbed and the toxicity appears.Letard and Sacy (1945) reported that when the powder containing 3% BHC was sprinkled over the cornea of rabbits eye for 5 days, eye mucous membranes and nose mucous membranes did not show any symptom nor were tears recognized.According to the author's experiment, many lacrimations and eye hemorrhages were noticed in the rats exposed to the dusts. Consequently these symptoms seem to depend on the stimuli to eye mucous membranes.Moreover, Uruno et al. (1949) did a minute physical examination of the workers (male 94, female 41) of the DDT manufacturing industry and found that about 1/3 of the workers suffered from functional disorders of the liver.

The Management of Uncomplicated Diabetes Mellitus

To investigate the potential role of fresh Carica papaya (C. papaya) leaf extract on haematological and biochemical parameters and toxicological changes in a murine model.In total 36 mice were used for the trial. Fresh C. papaya leaf extract [0.2 mL (2 g)/mouse] was given only to the test group (18 mice). General behavior, clinical signs and feeding patterns were recorded. Blood and tissue samples were collected at intervals. Haematological parameters including platelet, red blood cell (RBC), white blood cell (WBC), packed cell volume (PCV), serum biochemistry including serum creatinine, serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT) were determined. Organs for possible histopathological changes were examined.Neither group exhibited alteration of behavior or reduction in food and water intake. Similarly, no significant changes in SGOT, SGPT and serum creatinine levels were detected in the test group. Histopathological organ changes were not observed in either group of mice except in three liver samples of the test group which had a mild focal necrosis. The platelet count (11.33±0.35)×105/μL (P=0.000 04) and the RBC count (7.97±0.61)×106/μL (P=0.000 03) were significantly increased in the test group compared to that of the controls. However, WBC count and PCV (%) values were not changed significantly in the test group. The platelet count in the test group started to increase significantly from Day 3 (3.4±0.18×105/μL), reaching almost a fourfold higher at Day 21 (11.3×105/μL), while it was 3.8×105/μL and 5.5×105/μL at Day 3 and Day 21 respectively in the control. Likewise, the RBC count in the test group increased from 6×106/μL to 9×106/μL at Day 21 while it remained near constant in the control group (6×106/μL).Fresh C. papaya leaf extract significantly increased the platelet and RBC counts in the test group as compared to controls. Therefore, it is very important to identify those chemicals of C. papaya leaves as it can be recommended to be used as a medication to boost thrombopoiesis and erythropoiesis in humans and in animals in which these cell lineages have been compromised.