ࡱ> M bjbj== WWl       DH B!t!H DHF"(n"@""""""GGGGGGG$6I VKVG """""Gl<  ""Gl<l<l<" " "Gl<"Gl<Bl<B:F,  G":" sEH z ;+G G<H0DH5GRK;KGl<H H      OHES Literature Review 2/2000 Introduction This is the second issue of our review of recent scientific literature dealing with issues relevant to occupational health and environmental issues affecting the world-wide manganese industry (producers and users). The object of this review is to draw attention to papers dealing with topics which the Scientific Advisory Group (SAG) have judged to be of current and future relevance to our industry. A copy of each paper is held by IMnIs secretariat so that members can request copies of specific papers. We would appreciate all feedback on the publication, so that we can improve the service and make it more pertinent to member companies and other interested parties. Anne Tremblay Secretary General, IMnI Leif Andreassen Chairman, OHES Committee October 2000 _____________________________________ 25/00 Consequences of manganese replacement of copper for prion protein function and proteinase resistance Brown (D.R.) [e-mail :  HYPERLINK "mailto:drb33@cam.ac.uk" drb33 @ cam.ac.uk], Hafiz (F), Glassmith (LL), Wong (B-S), Jones (IM), Clive (C) and Haswell (SJ) The EMBO Journal, 2000, 19, 6, 11801186 The Prion Protein (PrP) binds copper and has antioxidant activity enhancing the survival of neurones in culture. The ability of the PrP to bind other cations was tested and it was found that only manganese could substitute for copper. Although initially manganese-loaded PrP exhibited similar structure and activity to copper-loaded PrP, after aging, manganese-loaded PrP became proteinase resistant and lost function. It was also found that manganese could be incorporated into PrP expressed by astrocytes and that this PrP was partially proteinase resistant. These results show that it is possible to generate proteinase-resistant PrP from cells and suggest a possible mechanism for the formation of the scrapie isoform of the PrP as generated in sporadic prion disease. 26/00 Hemoglobin and IronEvoked Oxidative Stress in the Brain: Protection by Bile Pigments, Manganese and SNitroso-glutathione Van Bergen (P), Rauhala (P), Spooner (CM) and Chiueh (CC) [email : chiueh @iielix.nih.gov] Free Rad Res, 1999, 31, 631-640 In the present in vitro and in vivo study we investigated the prooxidant effects of hemoglobin, as well as the antioxidant effects of its metabolites, in the brain. Incubation of rat brain homogenates with hemoglobin (010 M) but not hemin induced lipid peroxidation up to 24 h (EC50 = 1.2 M). Hemoglobin's effects were similar to ferrous ion (EC50 = 1.7 M) and were blocked by the chelating agent deferoxamine (IC50 = 0.5 M) and a nitric oxidereleasing compound Snitrosoglutathione (IC50 = 40 M). However, metabolites of hemoglobin  biliverdin and bilirubin  inhibited brain lipid peroxidation induced by cell disruption and hemoglobin (biliverdin IC50 = 1230 and bilirubin IC50 = 75170 M). Biliverdin's antioxidative effects in spontaneous and ironevoked lipid peroxidation were further augmented by manganese (2 M) since manganese is an antioxidative transition metal and conjugates with bile pigments. Intrastriatal infusion of hemoglobin (024 nmol) produced slight, but significant 2022% decreases in striatal dopamine levels. Whereas, intrastriatal infusion of ferrous citrate (024 nmol) dose-dependently induced a greater 66% depletion of striatal dopamine which was preceded by an acute increase of lipid peroxidation. In conclusion, contrary to the in vitro results hemoglobin is far less neurotoxic than ferrous ions in the brain. It is speculated that hemoglobin may be partially detoxified by heme oxygenase and biliverdin reductase to its antioxidative metabolites in the brain. However, in head trauma and stroke, massive bleeding could significantly produce ironmediated oxidative stress and neurodegeneration which could be minimized by endogenous antioxidants such as biliverdin, bilirubin, manganese and Snitrosoglutathione. 27/00 Implications for Atypical Antioxidative Properties of Manganese in Ironinduced Brain Lipid Peroxidation and Copperdependent Low Density Lipoprotein Conjugation. Sziraki (I), Rauhala (P), Koh (KK), Van Bergen (P) and Chiueh (CC) [email : Chiueh @helix.nih.gov] Neurotoxicology, 1999, 20, 23, 455466 Our group recently observed that manganese prevents oxidative brain injury in the ironinduced parkinsonian animal model. It has also been suggested that manganese retards while copper promotes the development of atherosclerosis. In this report, we provide further evidence to support a controversial notion that manganese is an atypical antioxidant. Among transition metals, Cu2+ and Fe2+ (0.1 to 125 M), but not Mn2+, converted hydrogen peroxide to reactive hydroxyl radicals via the Fenton reaction at pH 7.4. Iron's prooxidative rate is relatively slow, but it is accelerated further by ascorbate (50 M) in 37C Dulbeccos phosphate buffered saline. Moreover, Mn2+ (080 M) concentration dependently retarded diene conjugation of human low density lipoproteins stimulated by 5 M Cu2+. This new result is consistent with our recent finding that Mn2+ (0 to 20 M) does not initiate brain lipid peroxidation while it inhibits ironinduced peroxidation of polyunsaturated fatty acids. These unexpected manganese results are somewhat at odds with a prominent theory that manganese is a pro-oxidative transition metal. Furthermore, iron and copper induced free radical generation and lipid peroxidation are suppressed by lowering the incubation temperature; this suggests that hypothermia may decrease the oxidative stress and damage in vivo. In conclusion, normal dietary intake of manganese may protect cells and neurons from oxidant stress through the inhibition of propagation of lipid peroxidation caused by hydroxyl radicals generated by pro-oxidative transition metals such as iron and copper. Potential therapeutical uses of manganese, manganese SOD mimetics and hypothermia for protecting brain neurons and vascular endothelial cells against oxidative stress and damage have been successfully demonstrated in both animal models and clinical trials. 28/00 Manganese : a Transition Metal Protects Nigrastriatal Neurons from Oxidative Stress in the IronInduced Animal Model of Parkinsonism Sziraki (I), Mohanakumar (KP), Rauhala (P), Kim (HG), Yeh (KJ) and Chiueh (CC) Neuroscience, 1998, 85, 4, 1101-1111 It has been suggested that transition metals such as iron and manganese produce oxidative injury to the dopaminergic nigrostriatal system, which may play a critical role in the pathogenesis of Parkinson's disease. Intranigral infusion of ferrous citrate (0 to 8.4 nmol, i.n.) acutely increased lipid peroxidation in the substantia nigra and dopamine turnover in the caudate nucleus. Subsequently, it caused a severe depletion of dopamine levels in the rat caudate nucleus. In contrast to iron's prooxidant effect, manganese (up to 30 nmol, i.n.) causes neither lipid peroxidation nor nigral injury/doparnine depletion. Manganese (1.05 to 4.2 nmol, i.n.) dosedependently protected nigral neurons from iron-induced oxidative injury and dopamine depletion. Manganese also suppressed acute increase in doparnine turnover and contralateral turning behaviour induced by iron. In brain homogenates manganese (0 to 10 M) concentrationdependently inhibited propagation of lipid peroxidation caused by iron (0 to 5 M). Without the contribution of manganese superoxide dismutase manganese was still effective in sodium azide and/or heatpretreated brain homogenates. Surprisingly, iron but not manganese, catalysed the Fenton reaction or the conversion of hydrogen peroxide to hydroxyl radicals. The results indicate that iron and manganese are t%%o transition metals mediating opposite effects in the nigrostriatal system, as prooxidant and antioxidant, respectively. In conclusion, intranigral infusion of iron, but not manganese, provides an animal model for studying the pathophysiological role of oxidant and oxidative stress in nigrostriatal degeneration and Parkinsonism. The present results further suggest that the atypical antioxidative properties of manganese may protect substantia nigra compacta neurons from ironinduced oxidative stress. 29/00 Myocardial manganese elevation and proton relaxivity enhancernent with manganese dipyridoxyl diphosphate. Ex vivo assessments in normally perfused and ischemic guinea pig hearts Brurok (H), Skoglund (T), Berg (K), Skarra (S), Karlsson (JOG) and Jynge (P) NMR Biomed, 1999, 12, 364372 Manganese (Mn) dipyridoxyl diphosphate (MnDPDP) is the active component of a contrast medium for liver MRI. By being metabolized, MnDPDP releases Mn2+ which is taken up and retained in hepatocytes. The study examined whether MnDPDP elevates Mn content and enhances proton relaxivity in normal myocardium, but not in ischemic myocardium with reduced coronary flow and impaired metabolism. Isolated guinea pig hearts were perfused at normal flow or low flow, inducing global subtotal ischemia. Ventricular ATP and Mn contents, T1 and T2 were measured. At normal flow tissue Mn content increased from the control. level of 4.1 to 70.4 mol/100g dry wt with MnDPDP (3000 M), while lowflow perfusion with MnDPDP (3000 M) resulted in a Mn content of 16.6 mol/ 100 g dry wt. Prolonged ischemia (35 and 90 min) reduced tissue Mn down to the control level. T1 shortening closely paralleled myocardial Mn elevations during both normal and lowflow perfusion. The use of a Mn2+ releasing contrast agent like MnDPDP may be a promising principle in MRI assessments of myocardial function and viability in coronary heart disease by revealing a differential pattem of changes in T1 relative to coronary flow, cell Mn uptake and retention, ion channel function and metabolism. 30/00 Mechanisms of Action of Liver Contrast Agents : Impact for Clinical Use Clment (O), Siauve (N), Cunod(C-A), VuilleminBodaghi (V), Leconte (I), and Frija (G) J of Computer Assisted Tomography, 1999, 23, suppl. 1, S45 S52 New contrast agents for magnetic resonance imaging are continually being developed by pharmaceutical companies in order to better image the liver. These agents can be divided into hepatobiliary agents directed to the hepatocytes and nanoparticulate agents directed to the reticuloendothelial system. After intravenous injection, ail these agents concentrate in the liver and induce profound changes in signal intensity. Particulate agents induce predominantly a darkening of the liver parenchyma, while hepatobiliary agents induce a brightening. In both cases, liverlesion conspicuity is enhanced, leading to a better visualization of the lesion. After a brief description of the principal characteristics of the agents, this paper will attempt to summarize the utility of these agents for the detection and characterization of focal liver disease. 31/00 Increase in Signal Intensities on T1 Weighted Magnetic Resonance Images in Asymptomatic ManganeseExposed Workers Yangho (K) [email: yanghokm@nuri.net], Kim (KS), Yang (JS), Park (IJ), Kim (E), Jin (Y), Kwon (KR), Chang (KH), Kim (J-W), Park (SH), Lim (HS), Cheong (H-K), Shin (YC), Park (J) and Moon (Y) Neuro Toxicology 1999, 20, 6, 901908 Objectives : To clarify the clinical significance of increased signal intensities on T1 weighted magnetic resonance imaging (MRI) we performed a large-scale epidemiological study on asymptomatic manganese (Mn)-exposed workers with its focus on MRI. Methods : We randomly selected 121 male workers out of a total of 750 workers including Mnexposed, nonexposed manual, and nonexposed clerical workers in the factories. We studied environmental and biological monitoring, neurological examination, and MRI. Results : The proportion of workers with increased signal intensities among the exposed, the nonexposed manual workers, and the nonexposed clerical workers was 46.1%, 18.8%, and 0%, respectively. Especially, 73.5% of the welders showed increased signal intensities. In no subject, were clinical signs of manganism observed. The pallidal index correlated with blood Mn concentration. Conclusion : Increase in signal intensities on the T1-weighted image reflect recent exposure to Mn, but not necessarily manganism. At which increase of signal intensity, the progression of manganism from Mn exposure occurs, remains to be solved. 32/00 Manganese exposure in foundry furnacemen and scrap recycling workers Lander (F), Kristiansen (J) and Lauritsen (JM) Int Arch Occup Environ Health, 1999, 72, 546550 Objectives : Cast iron products are alloyed with small quantities of manganese, and foundry furnacemen are potentially exposed to manganese during tapping and handling of smelts. Manganese is a neurotoxic substance that accumulates in the central nervous system, where it may cause a neurological disorder that bears many similarities to Parkinson's disease. The aim of the study was to investigate the sources and levels of manganese exposure in foundry furnacemen by a combined measuring of blood-manganese (BMn) and manganese in ambient air (airMn). Methods : During a period of 16 months, AirMn and BMn (denoted exposure values) were measured involving 24 furnacemen employed in three small size foundries and 21 scrap recycling workers from one plant. In the study period, 18 furnacemen had BMn measured 34 weeks after decreasing or stopping exposure (denoted postexposure values). The reference group for the BMn measurements consisted of 90 Danish male subjects. Results: Furnacemen who work in insufficiently ventilated smelting departments inhale, absorb, and retain significant amounts of manganese in their blood (approx. 2.55 g/l above reference values) despite a generally low measured airborne level of manganese fumes (0.0020.064 mg/m3 ). The exposure values compared with postexposure values revealed a significant decrease in the BMn (on average 3.7 g/l) level of the most exposed furnacemen. Two persons in our study were suspected of suffering clinically subacute manganese intoxication as both had BMn levels beyond the normal limit (25 and 29 g/l, respectively). The potential problem disappeared completely after cessation of exposure, and the BMn levels decreased to 9.4 and 14.1 g/1, respectively. Conclusions : Risk assessment based on combined measurements of BMn and airMn seems to be valid in the interpretation of workers' hazard. Our study indicates that BMn may be a valuable parameter for estimating recent exposure (within 12 weeks). However, more knowledge is needed about the BMn level and its relation to neurological symptoms. 33/00 Are Current Biomarkers Suitable for the Assessment of Manganese Exposure in Individual Workers ? Apostoli (P), Lucchini (R) [email :  HYPERLINK "mailto:lucchini@ cci.unibs.it" lucchini @ cci.unibs.it] and Alessio (L) Amer J Ind Med, 2000, 37, 283290 Background : Whole blood and urinary manganese have been measured in occupational and environmental studies for the assessment of exposure. The aim of this study was to assess the relationship between the airborne concentrations of manganese and these biological indicators. Methods : Environmental and biological monitoring was performed in a group of 94 employees in a ferroalloy production, who were exposed to manganese (Mn) oxides (MnO2 and Mn304). The results were compared with those from a control group of 87 subjects not exposed to Mn. Results : Mn exposure levels ranged between 5 and 740 g/m3 with arithmetic and geometric mean and median values being 202.6, 97.6, and 150 g/m3 respectively. Arithmetic and geometric means for Mn in total blood (MnB) were, respectively, 10.3 3.8 and 9.7 g/l in the exposed and 5.9 1.7 and 5.7 g/l in the controls. For urinary Mn (MnU), arithmetic and geometric means were, respectively, 4.9 3.6 and 3.8 g/l in the exposed and 1.2 1.4 and 0. 7 g/l in the controls. On a group comparison, a significant relationship was found between high and low exposed subgroups, identified according to Mn atmospheric concentrations (MnA), for both MnB (F value = 38.0, P>0.0001) and MnU (F value = 36.1, P>0.0001). On a linear relationship, a correlation was observed between MnA and MnB (r = 0.34; r2 = 0.112; P= 0.001), whereas no association was found between MnA and MnU. A significant relationship emerged also between MnB and MnU (r = 0.48, r2 = 0.23, P < 0.0001). No association was observed between an index of cumulative exposure and the biological indicators of exposure. Conclusion : These results confirm that MnB and MnU can discriminate groups of occupationally exposed workers from groups of non-exposed subjects. MnB is also related to the intensity of external exposure on a linear relationship, but given a high variability, it is not suitable for individual biological monitoring. Therefore, further research should focus on more accurate biomarkers of Mn exposure. 34/00 Biomonitoring of manganese in blood, urine and axillary hair following lowdose exposure during the manufacture of dry cell batteries Bader (M), Dietz (MC), Ihrig (A), Triebig (G) Int Arch Occup Environ Health, 1999, 72, 521-527 Objectives : A crosssectional study was carried out on 100 workers from three different workplace areas in a dry cell battery manufacturing plant and on 17 currently non-exposed referents, to examine the relationship between the external exposure to manganese dioxide (Mn02) and the body burden of manganese in blood, urine and hair. Methods: Inhalable dust was measured gravimetrically after stationary active sampling. Manganese was analyzed in dust samples, blood, urine and axillary hair by atomic absorption spectrometry. Results: The average air concentrations of manganese in the three workplace areas were 4 g/m3 (range:112 g/m3), 40 g/m3 (1264 g/m3) and 400 g/m3 (137794 g/m3). Manganese in blood and axillary hair correlated with airborne manganese in groupbased calculations but not on an individual level. The manganese concentrations varied between 3.2 g/l and 25.8 g/lin the blood (mean: 12.2 4.8 g/l) and between 0.4 g/g and 49.6 g/g in hair (mean: 6.2 6.2 g/g in the proximal sequence), respectively. The results for the non-exposed referents were 7.5 2.7 g/l (mean) in the blood (range: 2.615.1 g/l) and 2.2 1.8 g/g (mean) in axillary hair (range: 0.4-6.2 g/g). In these matrices, manganese differed significantly between the highly exposed workers and both the reference and the lowexposure group. Manganese in blood revealed the lowest background variance. No differences for manganese in urine were observed between workers (mean: 0.36 0.42 g/l, range: 0.1-2.2 g/l) and referents (mean: 0.46 0.47 g/l, range: 0.11.7 g/l). Conclusions: Manganese in blood is a specific and suitable parameter for the biomonitoring of Mn02 exposure, although its validity is limited to group based calculations. Urinary manganese failed to allow a differentiation between exposed workers and referents. The suitability of manganese analysis in hair for biomonitoring purposes suffers from a relatively great background variation as well as from analytical problems. 35/00 Studies on the relationship between occupational exposure to manganese and serum Clara cell protein levels in shipyard workers Halatek (T), TrzcinkaOchocka (M), Matczak (W), Krajewska (B), WronskaNofer (T) and Rydzynski (K) Trace elements and Electrolytes 2000, 17, 1, 48-53 It is known that welding fumes affect epithelial Clara cells in distal bronchioles, which secrete Clara cell protein (CC 16). Therefore, measurement of CC 16 in serum could be used to evaluate the changes in number and/or integrity of lung epithelial Clara cells. We found that the decrease in serum CC 16 of the chronically exposed shipyard welders correlated negatively with welding fume levels, expressed by ambient air Mn concentration (r2 = 0.47). Moreover, reduced synthesis and/or removal of CC 16 by the Clara cells negatively correlated with Mn level in blood (r2 = 0.52). On the other hand, in heavily exposed welding fumes workers (>1 mg Mn/m3), increased serum CC16 level was observed, which correlated positively with Mn air levels (r2 = 0.85) and Mn concentration in urine (r2 = 0.38). In addition, positive correlation of CC16 with serum hyaluronic acid (HA) level (r2 = 0.44) was noted in this population. Thus, CC 16 might serve as a peripheral biomarker to assess the integrity of the bronchoalveolar/blood barrier in workers exposed to Mncontaining welding fumes. 36/00 Manganese Deposits in Patients with Biliary Atresia After Hepatic Porto-Enterostomy Ikeda (S), Sera (Y), Yoshida (M), Ohshiro (H), Uchino (S), Oka (Y), Lee (K-J) and Kotera (A) J Pediatr Surg 2000, 35, 3, 450453 Purpose : The aim of this study was to determine if there is latent manganese toxicity in patients with biliary atresia. Methods : Fifteen children with biliary atresia were examined postoperatively with regard to wholeblood manganese levels using brain magnetic resonance imaging (MRI) and I123 iodoamphetamine (IMP) par rectal portal scintigraphy. Results : Nine (60%) of the 15 had high wholeblood manganese levels (mean, 4.1 g/dL; range, 1.2 to 9.6; normal, 0.5 to 2.5), and these 9 had hyperintense globus pallidus on T1-weighted images, with no corresponding signal change in T2 sequences. I123 IMP per rectal portal scintigraphy was done for 13 patients to evaluate portosystemic shunt flow. 12 (92%) of these patients had an increased flow. Mean shunt ratio was estimated to be 41 % (range, 0.6to 98; normal, <5%). Encephalopathy was evident in only 1 patient. Conclusions: Some patients with biliary atresia in the postoperative period have manganese deposits in globus pallidus on T1weighted images and high wholeblood manganese levels, possibly caused by increased portsystemic shunt, and a latent or subclinical encephalopathy is also present. 37/00 Application of Mixed Models to Assess Exposures Monitored by Construction Workers During Hot Processes Rappaport (SM), Weaver (M), Taylor (D), Kupper (L) and Susi (P) Ann Occup Hyg, 1999, 43, 7, 457-469 Particulate exposures were assessed among construction workers engaged in hot processes in four jobs (boilermakers, ironworkers, pipefitters and welderfitters) at nine sites in the U.S. After being trained by occupational hygienists, the workers obtained shiftlong personal samples at each site for total particulates (TP). Selected samples were also assayed for manganese (Mn), nickel (Ni), and chromium (Cr). Workers provided information about process and taskrelated covariates that were present on the days of monitoring. Data were investigated with mixedmodel regression analyses that designated the jobs and covariates as fixed effects and the worker and error terms as random effects. Results indicated that the withinworker variance components, but not the betweenworker variance components, could be pooled among jobs. Mean air levels for a given agent varied by roughly six to 100 fold among the jobs, with boilermakers and ironworkers experiencing much higher levels of TP and Mn than pipefitters and welderfitters. Limited data also suggested that welderfitters were exposed to greater levels of Ni and Cr than pipefitters. Sufficient sample sizes were available to evaluate the effects of covariates upon exposures to TP and Mn. As expected, processes involving more than 50% hot work led to substantially higher levels of TP and Mn than those involving shorter durations of hot work. Localexhaust or mechanical ventilation reduced exposure to TP (but not Mn) by as much as 44%, and shielded or manual arc welding increased exposure to Mn (but not TP) by about 80%. Parameters estimated with these mixed models were used to calculate probabilities that workers were exposed at levels above U.S. occupational exposure limits (OELs). Regarding TP and Mn, these calculations suggested that 2695% of exposures to boilermakers and pipefitters and 213% of exposures to pipefitters and welderfitters exceeded the current Threshold Limit Values. Among welderfitters, limited data also pointed to probabilities of 250% for exceeding particular OELs for Ni and Cr. Using the significance of the estimated randomworker effects as a gauge for the uniformity of exposure within a job, administrative or engineering changes appear appropriate for reducing exposures to boilermakers and ironworkers, while individual personal environments should be investigated for pipefitters and welderfitters. 38/00 An In Vitro Model for the Assessment of Manganese Neurotoxicity Vettori (MV), Gatti ( R), Orlandini (G), Belletti (S), Alinovi ( R) Smargiassi (A) and Mutti (A) Toxycology in Vitro, 1999, 13, 931938 PC 12 (undifferentiated and differentiated) and C6 cells have been used to investigate kinetics, morphological and functional endpoints following exposure to MnCl2 and manganic transferrin (Mn-Tf). [Mn], in undifferentiated (nondifferentiated cells) exposed Io both free (MnCl2) and bound Mn (MnTf), was three to fivefold lower as compared to differentiated (differentiated) PC12 cells and higher by one order of magnitude as compared to glial C6 tells. Exposure to both MnCl2 and MnTf was followed by time and dosedependent morphological changes characteristic of apoptosis, which was never observed in Mnexposed C6 glial cells. Results from cell viability assays were consistent with apoptotic response rates quantified by cell count. Threshold concentrations for undifferentiated and differentiated PC12 cells were 106 and 105 M, respectively. Thus, despite their greater ability to accumulate Mn, differentiated PC12 cells are less sensitive to Mninduced apoptosis. This model might be relevant to neuronal degeneration induced by Mn occurring in the developing brain and possibly in clinical manganism. Such critical doses at the cellular Ievel seem to be consistent with Mn levels (5 x 10-6 M) recorded in the basal ganglia of monkeys chronically exposed to Mn and developing clinical signs of manganism. 39/00 Behavioral Effects of IntraNigral Microinjections of Manganese Chloride: Interaction With Nitric Oxide Ponzoni (S), Guimares (FS), Del Bel (EA) and Garcia-Cairasco (N) Prog NeuroPsychopharmacol & Biol Psychiat, 2000, 24, 307325. 1. Microinjection of manganese chloride (MnCl2) into the rat substantia nigra pars compacta (SNc) induces a neurodegenerative process manifested by apomorphineinduced rotational behavior. Manganese intoxication produces a parkinsonismlike phenotype in humans. 2. In addition to motor control the substantia nigra has also been proposed to be related to epilepsy and emotional behavior. 3. Although nitric oxide (NO) participation in neurodegenerative processes is still questioned, neurons stained for NAPDHdiaphorase, a marker of NOproducing cells, are spared in several experimental neuronal lesions. Additionally, NO has also been suggested to participate in motor control. 4. The objective of this study was to analyze the effects of Mn Cl2 induced nigral degeneration in audiogenic seizure susceptibility, anxiety and motor activity. We also analyzed if NO synthesis inhibition (NGnitroLarginine 25 mg/kg twice a day for 4 days) modifies Mn Cl2 induced neurodegenerative process. 5. Mn Cl2 (50 g) microinjection into the SNc caused a statistical significant higher number of apomorphine (0.75 mg/kg s.c.)induced rotations. No sensitization to audiogenic seizure was found but the lesion induced an increase of open arm exploration in the elevated plus maze, suggesting an anxiolytic affect. 6. The Mn Cl2nigral lesion was accompanied by an increased number of NADPHd positive neurons in the ipsilateral SNc and striatum (both sides). NO synthesis inhibition potentiated the Mn Cl2nigral Iesion and reversed the NADPHd cell number increase. The present results show that MnCl2nigral lesion can influence emotional behavior and suggest that NO may modify the progression of manganeseinduced degenerative process. 40/00 Contributo allo studio dei rapporti fra il contenuto in manganese della razione e l'insorgenza degli effetti della carenza di zinco nelle bovine da latte. Bonomi (A) La Rivista di Scienza dell'Alirnentazione, 1999, 28, 3, 321-332 Relationships between the manganese content of the ration and the rise of the effects of zinc deficiency in dairy cows. The Author refers the results obtained after researches carried out in three farms with the aim to verify the relationships between high manganese levels in the ration and the rise of the signs of zinc deficiency in dairy cows. Ninety Italian Fresian dairy cows were fed with rations containing a normal rate of zinc (50 p.p.m.) and manganese levels of 30 (control groups), 40, 60 and 80 p.p.m. In correspondence of the manganese level of 80 p.p.m., the cows showed a secondary zinc deficiency with a drop of plasma zinc content (from 90 to 70 g/100 ml), with the rise of lesions in the soft tissues of foot (digital and interdigital dermatitis, interdigital hyperplasia, interdigital phleamon) in a high percentage (47%), with a reduced reproductive efficiency (2,30 services per conception vs 1,65 of the control groups), with a drop in milk production (11 %) and with a rise (30%) of the incidence of the most frequent diseases (mastitis, ovarian cysts, metritis, silent estrus). The supply of the cows affected by the foot .syndrome with zinc carbonate (2 grams/head/day) has favourablv conditioned the recovery and the restitutio ad integrum of tissues in a shorter (P<0,05) time than control groups (20 vs 50 days). 41/00 The effect of excess dietary manganese on uninfected and Ascaridia galli infected chicks Gabrashanska (M), Tepavitcharova (S), Balarew (C), GalvezMorros (MM) and Arambarri (P) J of Helminthology, 1999, 73, 313316 The effect of dietary manganese from two different sources on chicks (uninfected and infected with Ascaridia galli) was studied. Chick diet was supplemented with 0.9 g Mn2+ kg1 food either in the form of MnSO4.H2O or 2Gly. MnCl2.2H20 for 20 days. Chicks were divided into six groups: group 0, control; group 1, control + MnS04.H2O; group 2, control + 2GIy.MnCl2.2H20; group 3, infected with A. galli; group 4, infected with A. galli + MnS04.H2O; and group 5, infected with A. galli + 2Gly.MnCl2.2H20. Body weight, mortality, worm burden, and liver manganese content were investigated. Excess dietary manganese increased weights and manganese level, but mortality and worm burden were unaffected. A greater bioavailability of manganese from 2Gly. MnCl2.2H20 was established. 42/00 Variations of manganese in the eggs of the Norway lobster, Nephrops norvegicus (L.) Eriksson (SP) Aquatic Toxicology, 2000, 48, 291295 The Norway lobster, Nephrops norvegicus, lives on sediments rich in manganese (Mn). Temporal fluctuations of Mn in th eggs of N. norvegicus was investigated, both in the field and in laboratory experiments. Female gonads and external eggs of different developmental stages were measured for Mn. The Mn concentration during oocyte maturation and throughout most of the embryogenesis (after fertilisation) remained stable around 5 g Mn g-1 dry wt. egg. At the end of the embryonic development (about 6 months after fertilisation) the Mn concentration of the egg started to increase and had at the time of hatching reached concentrations of 120 g Mn g-1 dry wt. egg. The egg shell was at this stage highly permeable and Mn was taken up by the embryo and egg shell in equal amounts. 43/00 Temporal variations of manganese in the haemolymph and tissues of the Norway lobster, Nephrops norvegicus (L.) Eriksson (SP) Aquatic Toxicology, 2000, 48, 297307 The Norway lobster, Nephrops norvegicus, lives on sediments rich in manganese (Mn) and any dissolved Mn2+ can readily be taken up by the animal. To investigate temporal fluctuations of bioavailable Mn, a N. norvegicats fishing ground on the Swedish west coast was repeatedly sampled every 2 months from September 1992 to November 1994. Tire Lobsters collected contained on average 91.7 g Mn g-1 dry wt. (S.E. 4.2, n = 156). The oxygen saturation of the bottom water proved to be negatively correlated with both the temperature of the water and the Mn (concentration and total content) of the animal's haemolymph. The temporal fluctuations in animal Mn load were however, small compared to spatial differences found in an earlier study. There was an increase in the Mn concentration of the lobster exoskeleton (from 56 to 340 g Mn g-1 dry wt. exoskeleton) and gills (from 34 to 160 g Mn g-1 dry wt. gill) in postmoult animals compared to premoult. The Mn concentrations of the lobsters' hepatopancreas and muscle tissue remained relatively constant throughout the moult cycle and appear to be more conservative in their Mn concentration and less affected by exposure to Mn. 44/00 A Pilot Study of Heavy Metal Concentration in Various Environments and Fishes in the Upper Sakarya River Basin, Turkey Barlas (N) [email: barlas@lidya.cc.hum.edu.tr] Environ Toxicol, 1999, 14, 367373 In this study, concentration of lead, cadmium, copper, cobalt, nickel, and manganese were measured in water, sediment, and fish (Cyprinus carpio and Barbus plebejus) samples at the upper Sakarya river basin in Sept. 19951996 period. Also, physical parameters of selected stations in the Sakarya river were measured. Mean concentrations of lead, cadmium, copper, nickel, and manganese differed between water, sediment, and fish samples by seasons. Mean concentrations of lead, cadmium, and cobalt increased in sediment samples in October and August. In water samples only cadmium and cobalt increased in October whereas lead and copper increased in August. Also, high levels of manganese concentrations were detected in water and sediment samples and fish tissue during the study. 45/00 Metals in Laysan Albatrosses from Midway Atoll Arch Environ Contam Toxicol, 2000, 38, 254259 Burger (J), Gochfeld (M) We examined the concentrations of lead, cadmium, selenium, chromium. manganese, arsenic, tin, and mercury in the heart, liver. kidney. salt gland, and feathers of adult (n = 10) and young (n = 15) Laysan albatrosses (Diomeden immutabilis) from Midway Atoll in the northcentral Pacific Ocean. Lead poisoning has been reported in some Laysans nesting near buildings on Midway, but other heavy metals have not been examined. We examined tissue distribution of metals by age and gender (adults only). We also examined tissue concentrations in three birds with a droopwing syndrome characteristic of lead poisoning. We compared metal levels in salt gland (a special excretory organ of marine birds) with those in other tissues. All metals varied significantly across tissues in both adults and chicks, and the relative tissue concentrations were similar in adults and chicks for most metals. Adults had higher levels of most metals in most organs, with significant differences mainly for cadmium (up to 20 x higher in kidney and salt gland) and for mercury (17 x higher in kidney). However, chicks had significantly higher manganese in liver and arsenic in salt gland. The salt gland had concentrations of most metals (except cadmium, selenium, and mercury) comparable to the kidney levels, which is consistent with it serving as an excretory organ for the cations. Chicks with droopwings had very elevated levels of lead in their tissue (16.8 ppm in feathers, 14 ppm in liver and kidney), whereas levels of other metals were not significantly different from the apparently normal chicks. 46/00 Quantitative Speciation of MnBearing Particulates Emitted from Autos Burning (Methylcyclopentadienyl) manganese Tri-carbonylAdded Gasolines Using XANES Spectroscopy Ressler (T), Wong (J), Roos (J), and Smith (IL) Environ Sci Technol, 2000, 34, 950958 The chemical nature of Mncontaining particulates emitted from (methylcyclopentadienyl) manganese tricarbonyl-added gasoline engines has been elucidated using Mn Kedge Xray absorption fine structure (XAFS) spectroscopy. Edge shift data from the Xray absorption nearedge structure (XANES) spectra showed that the average Mn valence in these particulates is ~2.2. Using a principal component analysis (PCA) algorithm, the number and type of probable species contained in these particulates were determined to be three, consisting of Mn3O4, MnSO4.H20, and a divalent manganese phosphate, Mn5(P04)[P03-(OH)]24H20. The proportions of these Mn phases in each particulate sample were evaluated quantitatively using leastsquares fitting (LSF) of the experimental XANES spectra with linear combinations of these principal component (model compound) spectra. Two groups of Mn-bearing particulates may be distinguished: group I having 49 wt % of Mn304 and exhibiting a single intense first major absorption maximum at the Mn Kedge and group II containing 1522 wt % of Mn304 and exhibiting a doublet absorption maximum at lower intensity. Fourier transforms of the EXAFS signals were found to corroborate the XANES results. This study clearly establishes XANES spectroscopy, in combination with PCA and LSF, as a quantitative analytical tool for speciation of dilute and/or amorphous multicomponent environmental materials not easily attainable with conventional methods. 47/00 Manganese and its compounds Williams-Johnson (M) Concise Intl Chem Assessment Doc, 1999, 12 NV:IV, 42 pages This CICAD on manganese and its compounds was based principally on the report entitled Toxicological Profile for Manganese (update), draft for public comment, prepared by the Agency for Toxic Substances and Disease Registry, US Dept of Health and Human Services (ATSDR, 1996). Information contained in the Hazardous Substances Data Bank, developed and maintained by the National Library of Medicine, US Dept of Health and Human Services, was also used (HSDB, 1998). Data identified as of Nov 1998 were considered in these source documents. Additional data came from other references, such as assessments prepared by the US Environmental Protection Agency (EPA) and the World Health Organisation (WHO), as well as a variety of reports in the literature. The source documents used to develop this CICAD do not cover the effects of manganese on the ecological environment.  No other sources (documents developed by national organisation and subject to rigorous scientific review) on this topic were identified. Therefore, this CICAD addresses environmental levels as a source of human exposure only. No attempt has been made in this document to assess effects on organisms in the environment. Information on the availability of the source documents is presented in appendix 1. Information on the peer review of this CICAD is presented in appendix 2. This CICAD was approved as an international assessment at a meeting of the final review board, held in Berlin, Germany, on 26-28 Nov 1997. Participants at the final review board meeting are presented in appendix 3. The Intl Chemical Safety Card (ICSC 0174) for manganese, produced by the international programme on chemical safety (IPCS, 1993) has also been reproduced in this document. Manganese (Mn) is a naturally occurring element that is found in rock, soil, water and food. Thus, all humans are exposed to manganese, and it is a normal component of the human body. Copyright IMnI October 2000 No part of this publication may be reproduced in any form whatsoever without obtaining IMnI's prior written consent. 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