Effects of manganese exposure on visuoperception and visual memory in schoolchildren.

BACKGROUND: Manganese (Mn) is an essential metal involved in multiple physiological functions. Environmental exposure to airborne Mn is associated with neurocognitive deficits in humans. Children, whose nervous system is in development, are particularly susceptible to Mn neurotoxicity. OBJECTIVE: The objective of this study was to assess the association between Mn environmental exposure, and effects on visuoperception and visual memory in schoolchildren. METHODS: We assessed schoolchildren between 7 and 11 years old, with similar socioeconomic status, from the mining district of Molango (n=148) and Agua Blanca (n=119, non-mining area) in Hidalgo state, Mexico. The Rey-Osterrieth Complex Figure (ROCF) test was used to assess visuoperception and short-term visual memory. Hair manganese (MnH) concentrations were determined. Linear regression models were constructed to estimate the associations between MnH and ROCF scores, adjusted for potential confounders. RESULTS: The geometric mean MnH was nine times higher in schoolchildren from the Mn mining area (5.25µg/g) than in schoolchildren from the non-mining area (0.55µg/g). For the ROCF Copy trial, MnH was significantly associated with an increase in distortion errors (tangency, closure), angle errors, overtracing (partial overtracing). In the Immediate Recall trial, MnH was significantly associated with increased overtracing (partial overtracing) and omissions, and negatively associated with the number of perceptual drawn units, total score and percentage immediate recall. CONCLUSIONS: MnH is associated with alterations in visuoperception and short-term visual memory in schoolchildren exposed to airborne Mn.

Manganese exposure and cognitive deficits: a growing concern for manganese neurotoxicity.

This symposium comprised five oral presentations dealing with recent findings on Mn-related cognitive and motor changes from epidemiological studies across the life span. The first contribution highlighted the usefulness of functional neuroimaging of the central nervous system (CNS) to evaluate cognitive as well as motor deficits in Mn-exposed welders. The second dealt with results of two prospective studies in Mn-exposed workers or welders showing that after decrease of Mn exposure the outcome of reversibility in adverse CNS effects may differ for motor and cognitive function and, in addition the issue of plasma Mn as a reliable biomarker for Mn exposure in welders has been addressed. The third presentation showed a brief overview of the results of an ongoing study assessing the relationship between environmental airborne Mn exposure and neurological or neuropsychological effects in adult Ohio residents living near a Mn point source. The fourth paper focused on the association between blood Mn and neurodevelopment in early childhood which seems to be sensitive to both low and high Mn concentrations. The fifth contribution gave an overview of six studies indicating a negative impact of excess environmental Mn exposure from air and drinking water on children's cognitive performance, with special attention to hair Mn as a potential biomarker of exposure. These studies highlight a series of questions about Mn neurotoxicity with respect to cognitive processes, forms and routes of exposure, adequate biomarkers of exposure, gender differences, susceptibility and exposure limits with regard to age.

Neurobehavioral functioning after cessation of manganese exposure: a follow-up after 14 years.

BACKGROUND: Little is known on the long-term course of early manganese (Mn) neurotoxic effects. Mn alloy workers were examined in a follow-up study 14 years after exposure ceased at a Canadian facility. METHODS: The same battery of neurofunctional tests used in the initial examination in 1990 was administered to 77 Mn-workers and 81 referents in 2004. RESULTS: Manganese-workers had poorer scores compared to referents both in the initial and follow-up examinations for several motor tasks of the Luria Motor Scale. At follow-up, older Mn-workers (>45 years at cessation of exposure) had poorer scores than referents for tests of cognitive flexibility. Cumulated exposure was associated with poorer test scores for certain neuromotor and cognitive tests and on a mood scale. Differences on certain tests observed at initial examination were not present at follow-up. CONCLUSIONS: Manganese exposure was associated with persistent deficits for certain neuromotor functions, cognitive flexibility, and adVerse mood states, while recovery occurred for other functions.

Decrease of soil fertility and release of mercury following deforestation in the Andean Amazon, Napo River Valley, Ecuador.

Soil erosion and degradation provoked by deforestation in the Amazon is a global concern, and recent studies propose a link between deforestation, soil erosion and the leaching of naturally occurring mercury (Hg). In the Ecuadorian Amazon, elevated deforestation rates and the proximity of volcanoes could play an important role in soil fertility and soil Hg levels. The goal of this study is to evaluate the impacts of deforestation on Andisol and Inceptisol fertility and Hg levels in the Napo River Valley, Ecuador. Results show a significant decrease in surface soil organic matter (-15% to -70% of C and N) and exchangeable cations (-25% to -60%) in deforested plots. Hg concentrations at the surface (0-5 cm), higher in Andisols (225 ng/g average) than in Inceptisols (95 ng/g average), show a decrease of up to 60% following deforestation. Soil erosion exposes the mineral horizon, a layer with a higher Hg burden, to the elements thus provoking and accelerating Hg leaching. These results suggest that deforestation and the associated Hg leaching could contribute to the fish Hg contamination measured in the Napo River watershed.

Very low level environmental exposure to lead and prolactin levels during pregnancy.

Lead (Pb) is a well-known poison interfering with calcium homeostasis and dopaminergic pathway. We hypothesized that environmental Pb exposure can interact with prolactin (PRL) secretion, regulated by calcium and dopamine, during pregnancy and in fetus. The objective of this longitudinal study was to determine the relationships between blood Pb concentration and serum PRL levels in 101 pregnant women recruited during pregnancy and their fetuses exposed to low environmental levels of Pb. We observed a significant negative relationship between maternal blood Pb concentrations and maternal serum PRL levels. Cord blood PRL was weakly correlated with blood Pb levels. Our results suggest that maternal physiological parameters in pregnancy can be modulated by low level of Pb exposure and indicate a particular susceptibility of pregnant women to its toxic effects.

Suicide and exposure to organophosphate insecticides: cause or effect?

BACKGROUND: Suicide using pesticides as agent is recognized as a major cause of pesticide poisoning. METHODS: A literature review of mortality and morbidity studies related to suicide among pesticide-exposed populations, and of human and animal studies of central nervous system toxicity related to organophosphate (OP) pesticides was performed. RESULTS: Suicide rates are high in farming populations. Animal studies link OP exposure to serotonin disturbances in the central nervous system, which are implicated in depression and suicide in humans. Epidemiological studies conclude that acute and chronic OP exposure is associated with affective disorders. Case series and ecological studies also support a causal association between OP use and suicide. CONCLUSIONS: OPs are not only agents for suicide. They may be part of the causal pathway. Emphasizing OPs solely as agents for suicide shifts responsibility for prevention to the individual, reducing corporate responsibility and limiting policy options available for control.

Blood manganese content at birth and cord serum prolactin levels.

Manganese (Mn) is both an essential element and, at a high dose, a potent neurotoxin that can interact with dopaminergic neurotransmission. Plasma prolactin (PRL), an indirect indicator of dopaminergic functioning, has been shown to vary with Mn exposure in adults, but little is known about this relation in the developing brain. The objective of this study was to examine the relations between maternal and cord Mn blood concentrations at birth and PRL cord blood levels. Blood Mn levels were determined in 87 pregnant women at delivery, and PRL was measured in the cord blood plasma. Mn cord blood concentration (mean 34.4 microg/l, range 16.7-89.4) was significantly and positively related to cord PRL levels. These findings suggest that Mn accumulation in utero could contribute to PRL level variation in neonates, which, in turn, may influence important developmental parameters.

Assessment of bioaccumulation and neurotoxicity in rats with portacaval anastomosis and exposed to manganese phosphate: a pilot study.

The use of the additive methylcyclopentadienyl manganese tricarbonyl in unleaded gasoline has resulted in increased attention to the potential toxic effects of manganese (Mn). Hypothetically, people with chronic liver disease may be more sensitive to the adverse neurotoxic effects of Mn. In this work, bioaccumulation of Mn, as well as histopathology and neurobehavioral damage, in end-to-side portacaval anastomosis (PCA) rats exposed to Mn phosphate via inhalation was investigated. During the week before the PCA operation, 4 wk after the PCA operation, and at the end of exposure, the rats were subjected to a locomotor evaluation (day-night activities) using a computerized autotrack system. Then a group of 6 PCA rats (EXP) was exposed to 3050 microg m(-3) (Mn phosphate) for 8 h/day, 5 days/wk for 4 consecutive weeks and compared to a control group (CON), 7 PCA rats exposed to 0.03 microg m(-3). After exposure, the rats were euthanized and Mn content in tissues and organs was determined by neutron activation analysis. The manganese concentrations in blood (0.05 microg/g vs. 0.02 microg/g), lung (1.32 microg/g vs. 0.24 microg/g), cerebellum (0.85 microg/g vs. 0.64 microg/g), frontal cortex (0.87 microg/g vs. 0.61 microg/g), and globus pallidus (3.56 microg/g vs. 1.33 microg/g) were significantly higher in the exposed group compared to the control group (p <.05). No difference was observed in liver, kidney, testes, and caudate putamen between the two groups. Neuronal cell loss was assessed by neuronal cell counts. The loss of cells in globus pallidus and caudate putamen as well as in frontal cortex was significantly higher (p <.05) for the EXP group. Assessment of the locomotor activities did not reveal any significant difference. This study constitutes a first step toward our understanding of the potential adverse effects of Mn in sensitive populations.

Color vision and occupational toluene exposure.

We examined the relationship between acquired color vision loss and exposure to toluene and total hydrocarbons among 125 male workers. Seventy-two toluene-exposed printers were compared with 34 workers from the same photogravure plant with ambient background exposure, and with 19 workers from a bookbinding plant located in the same town (nonexposed). Environmental mean toluene exposure level at workstation was estimated from individual 8-h sampling. Historic exposure data from the last 30 years were used to construct two cumulative exposure indices, one for toluene and one for total hydrocarbons. Airborne toluene levels were overall lower than the current Threshold Limit Value (TLV) of 50 ppm. Color vision was assessed by the Lanthony D-15 desaturated panel. Color vision loss was quantitatively established by the Color Confusion Index (CCI) and classified by type of acquired dyschromatopsia according to Verriest's classification. CCI was positively related to current airborne toluene levels, and cumulative exposure indices for toluene and total hydrocarbons (.18< or =r< or =.35). Odds ratios of acquired dyschromatopsia were significant for current airborne toluene, toluene, and total hydrocarbon past exposure (1.27 [1.02-1.58], 1.21 [1.04-1.39], 1.15 [1.02-1.31], respectively). In conclusion, this study suggests that the Lanthony D-15 desaturated panel detects early neurotoxic effects among workers exposed to toluene.

Neuropsychological dysfunction, mood disturbance, and emotional status of munitions workers.

The objective of this study was to compare the neuropsychological function, emotional status, visual function, and illness prevalence of 265 former munitions plant workers (M age = 56.7 years, M years of education = 12.07; 201 African American, 64 White) exposed to organic solvents for an average of 17.03 years with that of a group of 77 unexposed controls (M age = 51.3 years, M years of education = 13.07; 30 African American, 47 White). Neuropsychological tests were selected from the World Health Organization Neurobehavioral Core Test Battery, Wechsler Adult Intelligence Scale-III (WAIS-III), and Wechsler Memory Scale-III (WMS-III) and also included the Brief Symptom Inventory, Profile of Mood States, Beck Anxiety Inventory, and Beck Depression Inventory. Vision tests included the Lanthony d-15 color vision, the Vistech Contrast Sensitivity, and the Snellen. The exposed group showed greater deficits than the controls in verbal learning (WMS-III Logical Memory I Learning Slope and Word Lists I Recall), visuomotor tracking speed (Cancellation H, WAIS-III Digit Symbol-Coding) and psychomotor function (Dynamometer and Grooved Pegboard), and dysfunction in emotional status, illness prevalence, and visual function. African American workers reported higher levels of exposure than Whites. Exposure relations demonstrated increased neuropsychological dysfunction with increased exposure.

Sequential analysis of hair mercury levels in relation to fish diet of an Amazonian population, Brazil.

Several studies in the Amazonian Basin have shown that riverine populations are exposed to methylmercury through fish consumption. It has been suggested that seasonal variations in hair mercury observed through sequential analyses may be related to the changes in fish species ingested by the local communities. The aim of the present study was to investigate the relationship between fish-eating practices and seasonal variation in mercury exposure. A group of 36 women from a village located on the banks of the Tapajós River, a major tributary of the Amazon, comprised the present study population. An interview-administered questionnaire was used to gather information on socio-demographic characteristics, fish-eating practices and other relevant information. The women also provided hair samples of at least 24 cm in length for mercury analysis. Hair total and inorganic mercury concentration was measured using a cold vapor atomic absorption analytical method. Trigonometric regression analysis was done to assess the seasonal variation of total mercury levels. Variations in inorganic mercury were examined by repeated measures analysis of variance, and analysis of contrast variable with a polynomial transformation. The results showed that hair mercury levels varied with the season. Higher levels were observed in months corresponding to the dry season, with lower levels in the rainy season. Herbivorous fish predominated the diet for 47.2% of the women during the dry season, but this rose to 72.2% during the rainy season. Those who reported eating fish daily had higher mercury levels in hair compared to those who only ate fish a few times per week. Retrospective mercury analyses, evaluated by the quantity of mercury present in each centimeter of hair, indicate that mean mercury level of the population decreased over the 2 years prior to the study. The percentage of inorganic mercury over the total mercury in hair increased towards the extremities of the hair strand. Higher percentages of inorganic mercury were found for the group who ate more fish (on a daily consumption basis). These results support the assumption that there are seasonal variations in methylmercury exposure and also a relationship between type of fish species consumed and the resulting hair mercury levels.

Chronic nervous-system effects of long-term occupational exposure to DDT.

Dichlorodiphenyltrichloroethane (DDT) is a compound with moderate toxicity that is judged to be safe for occupational use, although little is known about its long-term effects on the human nervous system. We investigated chronic nervous-system effects of long-term occupational exposure to DDT by comparing the neurobehavioural performance of retired malaria-control workers with a reference group of retired guards and drivers. DDT-exposed workers did worse on tests assessing various neurobehavioural functions than controls; performance significantly deteriorated with increasing years of DDT application. Our results could not be explained by exposure to cholinesterase-inhibiting pesticides or other potential confounding factors.

Cumulative exposure to styrene and visual functions.

BACKGROUND: Results from a 1990-1992 longitudinal study of several reinforced plastics plants showed that for those workers whose styrene exposure had decreased, color vision (CV) improved; while near visual contrast sensitivity (CS) was poorer. METHODS: In 1999, we retested these visual functions in 18 workers with good visual acuity. A cumulative exposure index (CEI), corrected for respirator use, was calculated for each worker. RESULTS: Intra-individual comparison of mandelic acid (MA) showed a significant decrease over time (Friedman; P = 0.015), but current values were not related to CEI. For CV, no significant difference was observed between 1992 and 1999; present results were not related to MA or CEI. The CS profile decreased over time, with significant differences at 3 cpd (Friedman; P < 0.05). CS did not vary with MA levels, but was significantly depressed at the intermediate frequencies among those in the upper CEIH category (Kruskal-Wallis; P < 0.05). CONCLUSIONS: These findings suggest that CS loss increases with long-term cumulative exposure, reflecting chronic damage to the neuro-optic pathways.

[Association between work exposure to neurotoxic substances with workers' relationships with their social network]. / Liens entre l'exposition des travailleurs à des substances neurotoxiques et leurs relations interpersonnelles.

BACKGROUND: This study explored the impact on family life and social relations that may result from symptoms associated with exposure to neurotoxic substances in the workplace. We assessed the associations between exposure to neurotoxic substances in the workplace, workers'mental health, and workers'relationships with their social network. METHODS: A sample of 53 workers and their spouse completed a series of questionnaires, an interview on work history, and a structured interview assessing their personal relationships. Exposure to neurotoxic substances in the workplace were assessed by an interview, using a semiquantitative classification system. Mental health was measured with the Profile of Mood States (POMS), and marital satisfaction with the Marital Adjustment Test (MAT). The social network's characteristics were assessed with the Northern California Community Study Interview Schedule (NCCS). The associations between exposure and social networks were assessed with regression analyses. RESULTS: There were no associations between exposure and marital satisfaction. However, we found a negative association between workers'exposure and degrees of overlap between husbands' and wives' social networks (Pearson's correlation r=-0.27; p<0.05) and a positive association between exposure and workers' dependency on their support network (r=0.46; p<0.01). CONCLUSION: The results are discussed in terms of variables potentially linking exposure to social relationships as well as in terms of couples' vulnerability to marital distress among exposed workers.

Assessment of exposure to manganese in welding operations during the assembly of heavy excavation machinery accessories.

Welder exposure to metals in various industrial sectors is poorly characterized. We had the opportunity to carry out an exploratory study to characterize manganese exposure in welding operations in a recently established Quebec factory that assembled accessories for heavy excavation machinery. Ten workers were sampled for total manganese for at least two consecutive days out of three followed by two consecutive days for respirable manganese (with a size selective sampler with a median cut-off of 4 microns), during a typical week in the summer of 1998. Parts being welded were characterized as large or small. Small parts were those being welded on tables during subassembly. Workers were divided into two groups according to the parts they were welding. Seventy-eight percent of the total manganese exposure levels of welding operations during the assembly of large accessories of heavy excavation machinery exceeded the manganese American Conference of Governmental Industrial Hygienists (ACGIH) threshold limit value (TLV) of 0.20 mg/m3 (GM 0.24 mg/m3, n = 14) while none exceeded the TLV during the assembly of small pieces (GM 0.06 mg/m3, n = 8). Welding operations during the assembly of large heavy excavation machinery accessories may pose a significant health hazard. Considering the importance of task-related variables affecting exposure among workers, further studies are needed to better characterize exposure determinants of welding operations during the assembly of heavy excavation machinery accessories.

Mercury methylation along a lake-forest transect in the Tapajós river floodplain, Brazilian Amazon: seasonal and vertical variations.

The seasonal and spatial variations of net methylmercury production in sediments, soils and other sites were evaluated by assays with 203Hg at different depths and locations along a lake-forest transect at lake Enseada Grande, Tapajós river. Soil and sediment samples were taken at the surface and at different depths up to 9 cm. Fresh samples and acidified controls (1-3 g dry wt.) were slurried with local water and incubated in the dark at 25-28 degrees C for 3 days with 0.5-1.6 microg Hg g(-1) (dry wt.) added as 203HgCl2. CH3 203Hg was extracted and measured in scintillation cocktail after acid leaching. Methylmercury production varied by orders of magnitude among sites and among sediment or soil layers. Seasonal variations were smaller than those with sample depth and location. In both seasons, MeHg formation in sediment and soil or flooded soil decreased with depth and was, in the top layers, one order of magnitude higher in the C-rich littoral macrophyte zone (2.3-8.9%) and flooded forest (3.2-4.5%) than in the center of the lake (0.2-0.56%). Similar MeHg production was found in slurried dry soils (dry season) and in soils already flooded for months. In the macrophyte zone soil (dry season), methylation was mainly associated with the thin Paspalum sp. rootlet layer. In the forest site, vertical variation in methylation was less pronounced in flooded than in dry soils and during the inundation the higher methylation rate was found in the flocculent sediment settled over the litter layer. The roots of floating Paspalum sp. were an important Hg methylation site, particularly those heavily colonized with periphyton (3.4-5.4%). Methylation in surface or near-bottom water was undetectable (< 3 x 10(-2)%) at all sites. Flooded forests and macrophyte mats are specific features of the Amazon and are important links between Hg inputs from natural and manmade sources and MeHg exposure of local populations through fish intake.

Methylmercury exposure affects motor performance of a riverine population of the Tapajós river, Brazilian Amazon.

Gold mining and deforestation in the Brazilian Amazon are increasing mercury pollution of the extensive water system, exposing riverine populations to organic mercury through fish-eating. The aim of the present study was to evaluate the effect of such exposure on motor performance. This cross-sectional study was carried out in May 1996, in a village located on the banks of the Tapajós river in the Amazonian Basin, Brazil. Information concerning sociodemographics, health, smoking habits, alcohol drinking, dietary habits and work history were collected using an interview-administered questionnaire. Mercury concentrations were measured by cold vapor atomic absorption in blood and hair of each participant, of whom those aged between 15 and 79 years were assessed for motor performance (n = 84). Psychomotor performance was evaluated using the Santa Ana manual dexterity test, the Grooved Pegboard Fine motor test and the fingertapping motor speed test. Motor strength was measured by dynamometry for grip and pinch strength. Following the exclusion of 16 persons for previous head injury, working with mercury in the goldmining sites, or for diabetes, the relationship between performance and bioindicators of mercury was examined using multivariate statistical analyses, taking into account covariables. All participants in the study reported eating fish, which comprised 61.8% of the total meals eaten during the preceding week. The median hair total mercury concentration was 9 microg/g. Organic mercury accounted for 94.4 = 1.9% of the total mercury levels. Multivariate analysis of variance indicated that hair mercury was inversely associated with overall performance on the psychomotor tests, while a tendency was observed with blood mercury. Semipartial regression analyses showed that hair total mercury accounted for 8% to 16% of the variance of psychomotor performance. Neither hair nor blood total mercury was associated with the results of the strength tests in women and men. Although dose-effect relationships were observed in this cross-sectional study, they may reflect higher exposure levels in the past. The findings of this study demonstrated neurobehavioral manifestations of subtle neurotoxic effects on motor functions, associated with low-level methylmercury exposure.

Beyond the workplace: an exploratory study of the impact of neurotoxic workplace exposure on marital relations.

BACKGROUND: The impact on family life and social relations that may result from symptoms associated with exposure to neurotoxic substances has never been addressed. This exploratory study assessed the associations between exposure to neurotoxic agents in the workplace, mental health, and marital difficulties. METHODS: Fifty-five (55) male workers and their spouses completed standardized measures of mental health and marital difficulties. Workers' exposure to neurotoxic substances was evaluated by questionnaire and interview, using a semiquantitative classification system. RESULTS: A positive relation was observed between exposure level and measures of workers' psychological symptoms and marital stress; no relation was observed between workers' exposure level and wives' psychological symptoms. More severe exposure to neurotoxic substances was associated with wives' reports of more severe marital conflicts, and this association was mediated by husbands' psychological symptoms. As compared to low exposure husbands, high exposure husbands reported higher degrees of stress surrounding marital discussions, more consistent incidence of minor physical assaults by wives, and stronger associations between their levels of stress, the verbal aggressions of wives, and the number of marital conflicts. CONCLUSIONS: The results of this study confirm that neurotoxic exposure is a risk factor for mental health and suggest how this may influence marital relations. Because of the importance of these findings for the well-being of workers and their families, these associations should be further studied.

Cytogenetic damage related to low levels of methyl mercury contamination in the Brazilian Amazon.

The mercury rejected in the water system, from mining operations and lixiviation of soils after deforestation, is considered to be the main contributors to the contamination of the ecosystem in the Amazon Basin. The objectives of the present study were to examine cytogenetic functions in peripheral lymphocytes within a population living on the banks of the Tapajós River with respect to methylmercury (MeHg) contamination, using hair mercury as a biological indicator of exposure. Our investigation shows a clear relation between methylmercury contamination and cytogenetic damage in lymphocytes at levels well below 50 micrograms/gram, the level at which initial clinical signs and symptoms of mercury poisoning occur. The first apparent biological effect with increasing MeHg hair level was the impairment of lymphocyte proliferation measured as mitotic index (MI). The relation between mercury concentration in hair and MI suggests that this parameter, an indicator of changes in lymphocytes and their ability to respond to culture conditions, may be an early marker of cytotoxicity and genotoxicity in humans and should be taken into account in the preliminary evaluation of the risks to populations exposed in vivo. This is the first report showing clear cytotoxic effects of long-term exposure to MeHg. Although the results strongly suggest that, under the conditions examined here, MeHg is both a spindle poison and a clastogen, the biological significance of these observations are as yet unknown. A long-term follow-up of these subjects should be undertaken.

Long-term exposure to "low levels" of manganese oxides and neurofunctional changes in ferroalloy workers.

Occupational exposure to manganese can cause early neurobehavioral effects in low- or a-symptomatic workers. A battery of neuropsychological tests was administered to a group of 61 ferroalloy male workers and 87 controls. The average (geometric mean) manganese concentrations in total dust at the plant have changed from 1981 to 1997 respectively from 1597.03 micrograms/m3 to 239 micrograms/m3 at the furnace area; from 151.53 to 255.76 micrograms/m3 at the casting area; from 167 to 54.7 micrograms/m3 at the maintenance (welding operations), yielding a current overall value of 54.25 micrograms/m3. A cumulative exposure index was calculated for each alloy worker and the average value (geometric mean) resulted to be 1204.87 micrograms/m3 x years, which divided by the average length of exposure (15.17 years), showed the concentration of 70.83 micrograms/m3 of manganese in total dust. Blood and urinary manganese geometric means resulted significantly higher in the exposed workers (9.18 micrograms/l and 1.53 micrograms/g creatinine, respectively) than in controls (5.74 micrograms/l and 0.40 microgram/g creatinine, respectively). A positive correlation was observed between the airborne manganese concentrations in total dust and blood manganese (n = 55; R = 0.36; R2 = 0.13; p = 0.0068), whereas no association resulted between cumulative exposure index and both blood manganese and urinary manganese. Higher prevalence of symptoms reporting was observed in the alloy workers concerning irritability, loss of equilibrium and rigidity. Tremor parameters including the central frequency and its dispersion, resulted to be statistically different in the exposed workers compared to the controls. Motor functions exploring the coordination of rapid and alternating movements and memory functions resulted to be impaired in the manganese workers. Dose-effect relationships were observed between the cumulative exposure index and some of the test results, whereas no relationship was found with the airborne manganese concentrations and the biological indicators of exposure. These findings are consistent with the existing knowledge of a cumulative mechanism of action of manganese, which must be carefully considered when setting safe exposure levels. In order to be protective for the entire working life, the average annual exposure level should be lower than 100 micrograms/m3.