Motor Function, Olfactory Threshold, and Hematological Indices in Manganese-Exposed Ferroalloy Workers

Lucchini, Roberto; Bergamaschi, Enrico; Smargiassi, Audrey; Festa, D.; Apostoli, Pietro

doi:10.1006/enrs.1997.3702

Cited by 105 publications

(58 citation statements)

References 12 publications

(17 reference statements)

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“…divalent metal transporter 1; iron metabolism; manganese toxicity; lung metal absorption NEUROTOXIC EFFECTS OF MANGANESE due to occupational airborne exposures are well documented. Workers exposed to high concentrations often display a Parkinson's-like disorder called manganism (24,25,31,35). More recently, concern has been raised over the potential consequences of chronic low-level airborne exposures due to the introduction of methylcyclopentadienyl manganese tricarbonyl (MMT), a gasoline additive (3).…”

mentioning

confidence: 99%

Pharmacokinetics of pulmonary manganese absorption: evidence for increased susceptibility to manganese loading in iron-deficient rats

Heilig¹,

Molina²,

Donaghey³

et al. 2005

American Journal of Physiology-Lung Cellular and Molecular Phys

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of pulmonary manganese absorption: evidence for increased susceptibility to manganese loading in iron-deficient rats. Am J Physiol Lung Cell Mol Physiol 288: L887-L893, 2005. First published December 23, 2004; doi:10.1152/ajplung.00382.2004.-High levels of airborne manganese can be neurotoxic, yet little is known about absorption of this metal via the lungs. Intestinal manganese uptake is upregulated by iron deficiency and is thought to be mediated by divalent metal transporter 1 (DMT1), an iron-regulated factor known to play a role in dietary iron absorption. To better characterize metal absorption from the lungs to the blood and test whether iron deficiency may modify this process, the pharmacokinetics of pulmonary manganese and iron absorption by control and iron-deficient rats were compared. Levels of DMT1 expression in the lungs were determined to explore potential changes induced by iron deficiency that might alter metal absorption. The pharmacokinetic curves for intratracheally instilled 54 Mn and 59 Fe were significantly different, suggesting that pulmonary uptake of the two metals involves different mechanisms. Intratracheally instilled iron-deficient rats had significantly higher blood 54 Mn levels, whereas blood 59 Fe levels were significantly reduced compared with controls. The same trend was observed when radioisotopes were delivered by intravenous injection, indicating that iron-deficient rats have altered blood clearance of manganese. In situ analysis revealed the presence of DMT1 transcripts in airway epithelium; however, mRNA levels did not change in iron deficiency. Although lung DMT1 levels and metal absorption did not appear to be influenced by iron deficiency, the differences in blood clearance of instilled manganese identified by this study support the idea that iron status can influence the potential toxicity of this metal. divalent metal transporter 1; iron metabolism; manganese toxicity; lung metal absorption NEUROTOXIC EFFECTS OF MANGANESE due to occupational airborne exposures are well documented. Workers exposed to high concentrations often display a Parkinson's-like disorder called manganism (24,25,31,35). More recently, concern has been raised over the potential consequences of chronic low-level airborne exposures due to the introduction of methylcyclopentadienyl manganese tricarbonyl (MMT), a gasoline additive (3). Despite the importance of understanding the molecular basis for intoxication by airborne manganese, however, absorption of this metal from the lungs to the blood has yet to be fully explored.Divalent metal transporter 1 (DMT1), a transporter that interacts with both iron and manganese (12,21,22), is expressed by airway epithelial cells (36) and could be involved in active uptake of both metals by the lungs. Two of the known DMT1 mRNA isoforms contain iron-responsive elements (IREs) and are therefore subject to potential regulation by iron response proteins (23). Iron deficiency is known to be an important modifier of manganese absorption in the gut (8,9,20,26,37), an...

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confidence: 99%

Pharmacokinetics of pulmonary manganese absorption: evidence for increased susceptibility to manganese loading in iron-deficient rats

Heilig¹,

Molina²,

Donaghey³

et al. 2005

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…This can be converted to an equivalent human dose of 15 mg/m 3 over the same duration (Reagan-Shaw et al, 2008). Mn exposure in humans can originate from MMT emitted to the atmosphere during the combustion of gasoline, while high concentrations of Mn can also be detected in some working environments, where Mn concentrations of 0.093 mg/m 3 (Lucchini et al, 1997), 0.21 mg/m 3 (Myers et al, 2003), 0.948 mg/m 3 (Roels et al, 1992), 1.26 mg/m 3 (Jiang et al, 2007), 4.8 mg/m 3 , and even 35.7 mg/m 3 (Nakata et al, 2006) have been recorded.…”

Section: Discussionmentioning

confidence: 99%

Short-term manganese inhalation decreases brain dopamine transporter levels without disrupting motor skills in rats

et al. 2016

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-Manganese (Mn) is used in industrial metal alloys and can be released into the atmosphere during methylcyclopentadienyl manganese tricarbonyl combustion. Increased Mn deposition in the brain after long-term exposure to the metal by inhalation is associated with altered dopamine metabolism and neurobehavioral problems, including impaired motor skills. However, neurotoxic effects of short-term exposure to inhaled Mn are not completely characterized. The purpose of this study is to define the neurobehavioral and neurochemical effects of short-term inhalation exposure to Mn at a high concentration using rats. Male Sprague-Dawley rats were exposed to MnCl 2 aerosol in a nose-only inhalation chamber for 3 weeks (1.2 μm, 39 mg/m 3 ). Motor coordination was tested on the day after the last exposure using a rotarod device at a fixed speed of 10 rpm for 2 min. Also, dopamine transporter and dopamine receptor protein expression levels in the striatum region of the brain were determined by Western blot analysis. At a rotarod speed of 10 rpm, there were no significant differences in the time on the bar before the first fall or the number of falls during the two-minute test observed in the exposed rats, as compared with controls. The Mn-exposed group had significantly higher Mn levels in the lung, blood, olfactory bulb, prefrontal cortex, striatum, and cerebellum compared with the control group. A Mn concentration gradient was observed from the olfactory bulb to the striatum, supporting the idea that Mn is transported via the olfactory pathway. Our results demonstrated that inhalation exposure to 39 mg/m 3 Mn for 3 weeks induced mild lung injury and modulation of dopamine transporter expression in the brain, without altering motor activity.

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“…Lucchini et al (1997) reported finger tapping, symbol digit, digit span, and additions declines associated with external exposure. Myers et al (2003) reported digit-symbol, Luria-N item 1R performance associated with external exposure.…”

Section: Does Human Behavioral Neurotoxicology Research Address Risk mentioning

confidence: 99%

Neurobehavioral testing in human risk assessment

et al. 2008

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Neurobehavioral tests are being increasingly used in human risk assessment and there is a strong need for guidance. The field of neurobehavioral toxicology has evolved from research which initially focused on using traditional neuropsychological tests to identify "abnormal cases" to include methods used to detect sub-clinical deficits, to further incorporate the use of neurosensory assessment, and to expand testing from occupational populations to vulnerable populations including older adults and children. Even as exposures in the workplace are reduced, they have been increasing in the environment and research on exposure has now expanded to cross the entire lifetime. These neurobehavioral methods are applied in research and the findings used for regulatory purposes to develop preventative action for exposed populations. This paper reflects a summary of the talks presented at the symposium presented at the 11th meeting of the International Neurotoxicology Association.

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Motor Function, Olfactory Threshold, and Hematological Indices in Manganese-Exposed Ferroalloy Workers

Cited by 105 publications

References 12 publications

Pharmacokinetics of pulmonary manganese absorption: evidence for increased susceptibility to manganese loading in iron-deficient rats

Pharmacokinetics of pulmonary manganese absorption: evidence for increased susceptibility to manganese loading in iron-deficient rats

Short-term manganese inhalation decreases brain dopamine transporter levels without disrupting motor skills in rats

Neurobehavioral testing in human risk assessment

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