Maths Berlin

The Uptake of Mercury in the Brains of Mammals Exposed to Mercury Vapor and to Mercuric Salts

Rats, rabbits, and monkeys were exposed to mercury vapor (1 mg/cu m) for four hours, and uptake and distribution of mercury in the brain was compared with that of animals injected intravenously with the same dose of mercury as mercuric salts. Vapor-exposed animals showed a brain content about ten times higher than the injected animals. The results indicate that the higher uptake in brain following vapor exposure is a general phenomenon in mammals.

Dose-dependence of methylmercury metabolism. A study of distribution: biotransformation and excretion in the squirrel monkey

The distribution and excretion of different body burdens of methylmercury (MeHg) have been investigated in the squirrel monkey. In monkeys given weekly 0.8 mg/kg doses, orally, of 203-MeHg, a linear correlation was observed between the concentrations of radioactive Hg in the blood and brain to as much as a blood concentration of 1 mug/gm. Above this level, the ratio of concentration in the brain and blood was increased. The total Hg concentration in bile collected from the bile duct was 10% to 30% of that in blood, while the concentration in bile from the gallbladder approached that in the blood. The total Hg concentration in feces was always more than ten times that in urine. Biotransformation of MeHg to inorganic mercury has been demonstrated; in the liver about 20% of the total mercury was inorganic, in the kidney 50%, and in the bile 30% to 85%. In the brain less than 5% of the total mercury was inorganic. After a single 0.8 mg/kg dose, orally, of 203-MeHg, the halftime for total Hg in blood was 49 plus or minus 2.8 days, and in the whole body 134 plus or minus 2.7 days. During the first four days after dosing, the decrease in blood concentration was more rapid than that occurring later, due to a redistribution within tissue compartments. A differential distribution of MeHg within the brain has been demonstrated in animals that showed clinical signs of intoxication.

Neurotoxicity of Methylmercury in Squirrel Monkeys

Blood mercury was raised to levels exceeding 1,000 ng/gm by weekly oral doses of methylmercury hydroxide to squirrel monkeys. Operant behavior tests were employed and neurological signs were recorded on film. Sudden visual disturbance occured with subacute exposure. Prolonged exposure resulted in impaired coordination with impairment of scotopic vision and possibly also sensory disturbances. Scotopic vision was tested by determining the critical fusion intensity (cfi) at 10 cps. An increase in cfi was the earliest neurological sign appearing in some monkeys months before other signs could be detected. Poisoned monkeys exhibited typical cerebral cortical lesions. The visual cortex was invariably involved. Extension to adjacent cortical areas increased with increasing duration of exposure and increasing brain mercury. The microgram per gram brain tissue was the lowest concentration of methylmercury seen wiht morphological lesions.

Effects of Occupational Exposure to Lead on Sperm and Semen

Semen qualities were studied in samples from workers exposed to lead in a factory for storage batteries. The study included two groups with different degrees of exposure. The mean lead-blood concentration (Pb-B) values for the men in the two groups during the six months preceding the study were 45 µg/100 ml and 22 µg/100 ml, respectively. Each man delivered at least one semen sample during a test period and most of the men participated in both test periods, which took place within a six-month interval. The size of each of the four groups, was 16 or more men. The semen qualities assessed included sperm count, sperm motility (qualitative and quantitative), sperm morphology, sperm chromatin stability when exposed to sodium dodecyl sulphate, and release of LDH-X into the seminal plasma. The secretory function of the prostate was assessed by analyses of such markers as acid phosphatase, zinc, and magnesium. Fructose was used as the marker for the secretory function of the seminal vesicles. All semen samples had values within the expected limits for that population. A subtle but significant difference was found between the two groups for sperm chromatin stability, indicating that the exposure to lead had decreased the stability of the spermatozoa. Moreover, a decreased secretory function of the accessory genital glands was noted more frequently among the men with the higher degree of exposure than among those in the other group. For all other semen variables, there were no differences between the groups.

Toxic effects on mouse bone marrow caused by inhalation of benzene

Male NMRI mice were exposed to benzene in air, concentrations ranging between 1–200 ppm. The following parameters in the bone marrows were examined:1. number of nucleated cells/tibia, 2. number of colony forming granulopoietic stem cells (CFU-C)/tibia, and 3. frequency of micronuclei in polychromatic erythrocytes.At continuous exposure as low benzene concentrations as 21 ppm during 4–10 days significantly affected the three parameters. Intermittent exposure (8 h/day, 5 days/week, 2 weeks) also resulted in measurable toxicity, particularly on number of CFU-C/tibia and frequency of micronuclei, at 21 ppm and higher doses. Short peak exposures had very limited effects but did increase the proliferation rate of the bone marrow, i.e., the number of CFU-C/105 cells became elevated.

Mercury distribution in the rat brain after mercury vapor exposure.

Brown Norwegian rats were exposed to mercury vapor at a concentration of approximately 1 mg/m3 for 5 weeks 24 hr/day 7 days a week and 6 hr/day 3 days a week, respectively. The total mercury absorption was calculated to 264 and 35 micrograms per week and 100 g body weight. The mean blood mercury concentration was 0.25 +/- 0.03 and 0.09 +/- 0.01 microgram/g, and the total concentration in the brain was 5.03 +/- 0.73 and 0.71 +/- 0.10 microgram/g tissue, respectively. The mercury distribution in the brains was examined using a method based on chemographic principles. Mercury was found primarily in the neocortex, in the basal nuclei, and in the cerebellar Purkinje cells. This distribution pattern corresponded to the pattern of inorganic mercury described after exposure to methyl mercury. Distribution of mercury after administration of different mercury compounds is discussed.

Autoimmune glomerulonephritis induced by mercury vapour exposure in the Brown Norway rat.

Subcutaneous injections of mercuric chloride induce an autoimmune glomerulonephritis with both granular and linear IgG deposits along the glomerular capillary wall and proteinuria. This disease is due to a T cell dependent polyclonal B cell activation responsible for production of antibodies against self (glomerular basement membrane, immunoglobulins, DNA, myeloperoxydase) and non self (sheep red blood cells, trinitrophenol (TNP)) components. Increase in serum IgE concentration is the hallmark of this disease. To determine if mercury vapours have pathogenic effects is an important problem of public health. The aim of this study was, first to compare the effects of mercury vapour exposure to those of mercury injections and, second, to compare the effects of high doses to those of low doses of mercury. Two exposure levels were studied corresponding to a mercury absorption of 13.1 mumol/week per kg body wt. and 1.7 mumol/week per kg body wt. during a 5-week period. It will be shown that, whereas the mercury concentration in the kidneys was similar in injected--and vapour exposed--rats, the mercury concentration in blood at the end of the exposure was about twice as high in the injected animals. Blood concentration of mercury was related to dose level but kidney content of mercury was similar in all groups, in spite of a dose difference by a factor of seven between low and high exposure. Mercury vapour and HgCl2 injections both trigger autoimmunity to the same extent and, in both cases the extent of autoimmune manifestations was dose-dependent.

Tritiated methylmercury in the brain of squirrel monkeys.

Tritiated methylmercuty hydroxide (MeHgOH) with a specific activity of 306 curies/mol was synthesized by a Grignard reagent from tritiated methyl iodide with a yield of 70%. Tritiated MeHg was given to squirrel monkeys by stomach tube in weekly doses of 0.8 mg/kg. The animals were killed after one dose or six doses. The distribution of the substance in the brain was then studied by microautoradiography and by fractionation of brain tissue into cellular and subcellular fractions. Part of the MeHg in the brain is in a water-soluble form. Methylmercuty was found autoradiographically mainly in the neuropile of the cortex. At subtoxic doses (one dose), more protein-bound radioactivity was found in the glial fraction than in the neuronal fraction. At toxic dose (six doses), the protein-bound fraction of MeHg increased significantly (P less than .02) in the neurons relative to nontoxic dose (one dose). Methylmercury was demonstrated autoradiographically in damaged neurons but not in undamaged neurons.

Pathological changes in the Brown Norway rat cerebellum after mercury vapour exposure

Our previous studies have demonstrated that mercury vapour exposure of Brown Norway rats induced an autoimmune response with development of glomerulonephritis and resulted in mercury deposition in the central nervous system, particularly in the neurons. The aim of this study was to investigate the effect on the central nervous system. A loss of Purkinje cells accompanied by Bergmann glial cell proliferation was found at a brain mercury level of 0.71 micrograms/g and became even more pronounced as the exposure dose increased. At a brain mercury level of 5.0 micrograms/g, a heavy gliosis was present in the brain stem, particularly around the pontine nuclei. In comparison with our previous study, the pathological changes in the brain appeared at the same mercury exposure dose as the glomerulonephritis. However, the location of pathological changes at the mercury level of 0.71 micrograms/g was not completely in accordance with the mercury distribution in the brain, which might be due to the sequence of mercury deposition, its amount or the vulnerability of the various cells classes.

Bone Marrow Changes in Chronic Cadmium Poisoning in Rabbits

Cadmium poisoning produces microcytic hypochromic anemia in rabbits. Parenteral administration of iron is followed by regression of this anemia. Femoral bone marrow was studied quantitatively in cadmium-poisoned and control rabbits with and without iron therapy. Data are tabulated. (C.H.)