Reproductive toxicity in male mice after exposure to high molybdenum and low copper concentrations.

To evaluate the effects of dietary high molybdenum (HMo) and low copper (LCu) concentrations on reproductive toxicity of male mice, 80 mice were divided into 4 groups of 20. These groups were fed with the following: (1) normal control (NC) diet (NC group); (2) NC and HMo diets (HMo group); (3) LCu diet (LCu group); and (4) HMo and LCu diets (HMoLCu group). On the 50th and 100th day, superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC) were analyzed to determine oxidative stress states. Morphological changes in testicular tissue were evaluated with hematoxylin and eosin staining and ultrastructural changes were monitored by transmission electron microscopy. The results showed that administration of HMo, LCu, and HMoLCu not only decreased sperm density and motility but also increased the rate of teratosperm occurrence. A significant increase in MDA content and a decrease in SOD, GSH-Px, and T-AOC contents were observed in LCu, HMo, and HMoLCu groups. Testicular tissues and cells of mice were damaged by HMo and the damages were more serious in the case of Cu deficiency. Exposure to HMo adversely affected the reproductive system of male mice, and dietary LCu plays key roles in HMo-induced reproductive toxicity.

Modest copper supplementation blocks molybdenosis in cattle.

It is widely accepted that ratios of dietary copper (Cu) to molybdenum (Mo) lower than 10:1 may produce molybdenosis in cattle, especially if sulfur concentrations are more than 3,000 ppm. Some authorities suggest that dietary Mo concentrations greater than 10 ppm are hazardous to cattle regardless of Cu concentration, but anecdotal reports suggest that this may not be the case. The original purpose of the experiment described in this report was to investigate whether supranutritional supplemental Cu could protect cattle against relatively high dietary Mo. Pregnant cows were grazed on 1 of 3 pastures: 1 with only background Mo, 1 with an average of 13 ppm Mo, and 1 that averaged 230 ppm Mo. Half the cows on the Mo pastures were supplemented with 17 ppm dietary Cu, the other half with the dietary supplement plus Cu boluses. Molybdenum effects were anticipated in the groups supplemented with 17 ppm Cu; however, despite increased tissue concentrations of Mo, only the 230 ppm Mo/17 ppm Cu group exhibited any effects. Moderate Cu supplementation permitted cows to graze a site heavily contaminated with Mo with no adverse effects on general health or reproduction.

Studies of a naturally occurring molybdenum-induced copper deficiency in the yak.

The clinical signs of a disorder known locally as "shakeback disease" in yaks in the North of the Qing Hai-Tibetan Plateau of China were defined: they included emaciation, unsteady gait, a 'shivering' back and deprived appetites. Coat colour was not affected. The mineral composition of soil and forages, and samples of blood and hair from yaks in affected ranches in this region were compared with those of 20 samples from unaffected areas. The mean concentration of molybdenum (Mo) in soil and forage was 4.85+/-0.21 and 4.96+/-0.25 microg/g (dry matter), respectively; the mean copper (Cu) to Mo ratio in the forage was only 1.34+/-0.36 compared to 8.12+/-1.31 for unaffected areas. The mean concentrations of Cu in blood and hair from the affected yaks were 0.29+/-0.17 and 3.51+/-1.12 microg/g, respectively, compared with 0.85+/-0.24 and 6.42+/-1.21 microg/g, for controls. The highest value for Cu in the blood of affected yaks was 0.58 mug/g and the lowest 0.03 microg/g (the corresponding highest values for unaffected yaks were 1.03 mug/g, the lowest 0.56 microg/g). There was a hypochromic microcytic anaemia and a low level of ceruloplasmin in the blood. The Cu deficiency in yaks was most severe during pregnancy and lactation, but oral administration of copper sulphate prevented and cured the disease. We conclude that "shakeback disease" of yaks in this region is probably caused by a secondary Cu deficiency, mainly due to the high Mo content in soils and forage.

A case report of acute human molybdenum toxicity from a dietary molybdenum supplement--a new member of the "Lucor metallicum" family.

The paper gives a brief review of human molybdenum metabolism and toxicity and presents the first known case of acute clinical poisoning with molybdenum from the dietary molybdenum (Mo) supplement in a male patient in late thirties. In over 18 days, the patient had consumed a cumulative dose of 13.5 mg Mo (300-800 micrograms Mo/day). Followed the development of acute psychosis with visual and auditory hallucinations, a series of petit mal seizures, and one life threatening grand mal attack. The symptoms remitted several hours after the start of chelation therapy with calcium ethylene diamine tetraacetic acid (CaEDTA). A battery of neuropsychological tests and Spectral Emission Computer Tomography demonstrated evident frontal cortical damage of the brain. One year after the Mo poisoning, the patient was diagnosed toxic encephalopathy with executive deficiencies, learning disability, major depression, and post-traumatic stress disorder. The paper strongly advocates issuance of and strict adherence to written warnings on the instruction labels not to mix potentially harmful neurotoxic substances, such as molybdenum, with other nutriceuticals and to instructions stating maximal single and cumulative doses. Molybdenum is a new and unwelcome member of the "metal madness" family.

[Experimental model for the study of molybdenosis in the primary copper deficiency in rats]. / Modelo experimental para el estudio de la molibdenosis y de la deficiencia primaria de cobre en ratas.

An experimental model in rats was evaluated to differentiate the effects between Copper deficiency and Molybdenosis. Sixty weaning rats (30 male and 30 female) received a diet with 70% complete powder milk (1 ppm Cu) and 30% maize meal (0.8-1.5 ppm Cu). Three experimental groups received the following mineral supplementation: copper deficiency (40 ppm Fe), molybdenosis (40 ppm Fe + 40 ppm Cu + 500 ppm Mo) and control (40 ppm Fe + 40 ppm Cu). The animals were weighed each 14 days. At 70 days of treatment were sacrificed. Blood and liver were sampled for analyzing hematocrit, ceruloplasmin activity and Cu and Mo liver concentration. Copper deficiency group had less serum ceruloplasmin activity. Cu and Mo liver concentration were higher in the animals with molybdenosis. We concluded that when Cu levels are higher than minimum requirement, feeding with high Mo, do not affect ceruloplasmin activity. In addition, high Mo liver concentration allows us to elucidate effects "per se" of molybdenosis.

Molybdenum poisoning in feedlot cattle.

OBJECTIVE: To describe a case of acute, fatal molybdenum poisoning in feedlot cattle. DESCRIPTION OF THE HERD: In total, 831 Hereford, Hereford x Angus, and Hereford x Simmental steers, aged 8 to 10 months, with an average body weight of 310 kg were fed a diet, to which sodium molybdate at a rate of 1.9% of the total ration had been accidently added. INVESTIGATION: The steers lost appetite within 3 days and deaths commenced within 6 days of the diet being first offered. The error was rectified when deaths started to occur, but steers continued to die for up to 7 months afterwards. Of the 831 steers on the feedlot, 90 died and a further 5 remained in poor condition. The cause of death was periacinar to massive hepatic necrosis and acute renal tubular necrosis. Blood and tissue samples were taken from surviving steers for 76 days, by which time plasma molybdenum concentrations had returned to normal concentrations. CONCLUSION: Sodium molybdate when fed at a rate of 1.9% of the diet results in acute renal tubular necrosis and periacinar to massive hepatic necrosis.

Copper deficiency in cattle, sheep and horses caused by excess molybdenum from fly ash: a case report.

A case of copper deficiency or molybdenum toxicosis in cattle, sheep and horses after heavy pollution of a pasture with fly ash is described. If the pastures had not been grazed by cattle and sheep as well as the horses, it would have been difficult to identify the reason for the intoxication in the horses. It is argued that molybdenum intoxication, although seldom seen in non-ruminants, was the cause of the deaths of the horses. It is suggested that the bioavailability of molybdenum in fly ash is high and therefore can cause equine intoxication.

Lung cancer mortality among a cohort of male chromate pigment workers in Japan.

In 1975, five manufacturers of chromate pigment in Japan were examined in a study of the carcinogenicity of chromates. These companies were producing lead chromate, zinc chromate, molybdate orange and/or strontium chromate. The current study covers a cohort of 666 workers involved in the manufacture of chromate pigment for at least 1 year between 1950 and 1975. The workers were followed up for 15-40 years, until 1989. Many previous reports have found an excess lung cancer risk among workers involved in the manufacture of chromate pigments and chromate chemicals. In the current study, subjects were classified on the basis of years worked, years of observation, characteristics of company, type of work engaged in for the longest period of time, and involvement in the manufacture of zinc chromate. Mortality was compared with that of all Japanese males by means of the person-year method. The route of exposure was primarily inhalation through the respiratory system. None of the results showed statistically significant differences that would suggest an excess risk for malignant neoplasms, particularly lung cancer, among workers engaged in the manufacture of chromate pigment in Japan.

[The enzymatic chemical mechanisms of adaptation]. / K voprosu o nekotorykh énzimokhimicheskikh mekhanizmakh adaptatsii.

In sheep from biogeochemical provinces enriched by molybdenum and copper and in a model form of molybdenum toxicosis in animals, the important role of enzymic and neurohumoral systems in the development of adaptation to excessive uptake of molybdenum and copper has been demonstrated. Adaptive reorganization of the activity of enzymic systems (xanthine oxidase, ceruloplasmin, succinate dehydrogenase, aspartate and alanine aminotransferases) and gradual involvement of neurohumoral mechanisms of the sympathoadrenal and cholinoreactive systems provide for adaptation of some animals in molybdenum and copper-molybdenum biogeochemical provinces. In other sheep, under the same conditions, dystonic disturbances in the vegetative nervous systems are observed together with the development of molybdenum toxicosis.

Hematological and plasma biochemical disturbances in experimental molybdenum toxicosis in sheep.

Two groups of 4 sheep received a daily iv injection of sodium heptamolybdate (100mg/day) or of saline for 2 weeks to study the hematological and plasma biochemical effects of molybdenum toxicosis. In molybdenum-dosed sheep, there was hypercupremia, mild anemia due to the decrease of copper concentration in the liver and moderate hepatocellular damage probably due to a direct toxic effect of molybdenum against the liver.

Apport de la toxicologie veterinaire a la matiere medicale / Veterinary toxicology contribution to materia medica

VERATRUM ALBUM(le veratre blanc) est une liliacee, dont la tige, les feuilles et le rhizome renferment des alcaloides tres toxiques resistant a la dessication (foin). L'intoxication grave evolue vers la mort en quelques heures. Elle comporte des symptomes cardiovasculaires, nerveux, digestifs, respiratoires et urinaires. Le traitemente de l'animal intoxique est symptomatique. La comparaison de l'intoxication chez l'animal avec la Matiere Medicale de Lathoud montre que les modalites des symptomes digestifs et cardiovasculaires sont fidelement retrouves alors qu'aucun symptome pulmonaire, ni urinaire n'est decrit dans cette Matiere Medicale. HYPERICUM PERFORATUM(le millepertuis officinal) est une plante dont l'ingestion entraine au bout de quelques heures une photosensibilisation pruriante, voisine du fagopyrisme (sarrain). On observe des symptomes de photodermite sur les zones depigmentees ou a peau fine (prurit, oedeme, sensibilite a l'eau froide et au toucher) et parfois, des symptomes de keratite et de conjonctivite. Le traitement consiste principalement ennune mise a l'ombre de l'animal. La comparaison de cette intoxication chez l'animal avec la Matiere Medicale de Lathoud montre qu'aucun symptome semblable n'est decrit chez l'homme, si ce n'est peut-etre l'extreme sensibilite au toucher. MOLYBDENE. La carence en cuivre des vegetaux et du sol augmente la toxicite de Molybdene qui devient dangereux dans les fourages a teneus normale principalement pour les jeunes bovins (2 a 6 mois). Les signes digestifs (diarrhee acqueuse persistante), osseux, cutanes et generaux disparaissent quand on augmente les teneurs en cuivre de la ration. La pathogenesie du Molybdene n'est exposee que dans la Matiere Medicale de Julian ou nous ne retrouvons aucun des symptomes decrits chez l'animal intoxique

Copper supplementation of drinking water for cattle grazing molybdenum-rich pastures.

A field trial was carried out with young cattle grazing molybdenum-rich pastures to test the efficacy of supplying copper salts in drinking water. One group was given two copper injections and 1.8 kg barley supplemented with 125 mg/kg copper, while the other received drinking water containing 2 to 3 mg/litre copper as copper sulphate supplied by means of a proportioner. The results demonstrated that this low concentration of copper in the water was effective in maintaining normal blood levels and in preventing scouring and subsequent loss of condition. The proportioner was capable of finely controlling the level of copper added to the water.

5-Nucleotidase in liver injury induced by heavy metals. A histochemical study.

The alterations in the distribution of 5-nucleotidase being the indicator of the functional state of liver parenchyma have been determined histochemically in the rat (Rattus rattus albino) after experimental poisoning with a few heavy metals viz. lead, mercury, cadmium, molybdenum, copper, and zinc that possess considerable environmental and nutritional significance. Present results show that all these metals affected the distribution and activity of 5-nucleotidase that has been explained on the basis of binding affinity of these metals, state of plasma membrane, resorption of nucleotides and variations in the level of enzyme protein. Presumably, all these factors have implications for the interpretation of observed changes in enzyme activity and are specific to each metal.

Zinc deficiency in molybdenum poisoned cattle.

Clinical signs ascribable to zinc deficiency were noted in a group of Friesian cows industrially poisoned with molybdenum. Zinc, copper, and molybdenum were determined in blood serum and black hair, and in the contaminated alfalfa pasture the group grazed on. Hematological parameters, and serum calcium and alkaline phosphatase activity, were also determined. Pooled samples of alfalfa from 2 uncontaminated pastures, and of blood, serum and black hair of clinically normal Friesian cattle grazing on these were used as controls. A mixed contamination of the polluted pasture with molybdenum and copper was found, both metals being inversely correlated with he distance to the polluting chimney. Zinc concentrations were normal and not significantly correlated with the distance to the chimney very high molybdenum was found in serum and hair of the poisoned animals; copper was normal in serum and hair. Low calcium and Alkaline phosphatase activity were found in serum, both variables being significantly correlated with serum zinc. Reduced red blood cell number, packed cell volumes and hemoglobin concentrations were also found, but no significant correlation of these parameters with any of the trace metals in serum or hair was found. Signs ascribed to zinc deficiency were consistent with the reduction of zinc in serum and hair and decreased alkaline phosphatase activity in serum. A zinc deficiency conditioned by a simultaneous increased intake of molybdenum and copper is proposed.