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A Mutti

Publications and source records attributed to A Mutti.

At least 37 records · Page 2Linked to original sources

Determination of n-hexane metabolites by liquid chromatography/mass spectrometry. 1. 2,5-hexanedione and other phase I metabolites in untreated and hydrolyzed urine samples by atmospheric pressure chemical ionization.

The capabilities of atmospheric pressure chemical ionization liquid chromatography/mass spectrometry (APCI-LC/MS) were investigated for the analysis of urinary 2,5-hexanedione (2,5-HD) and for the identification and characterization of other n-hexane Phase I metabolites in hydrolized urine samples. Chromatography was performed under reversed phase conditions at 0.75 mL min-1 flow rate. The ionization of 2,5-HD and other n-hexane metabolites was obtained in positive ion mode. After optimization of several interface parameters, the linearity, sensitivity and precision of the method were determined operating in the selected ion monitoring mode. Detection limits were 0.02 and 0.05 mg L-1 in water and urine respectively, with linear calibration curves in the 0.05-10 L-1 concentration range. Repeatability and both intra-day and inter-day precision were determined at two concentration levels (0.5 and 5.0 mg L-1), and relative standard deviations were in the 1.3%-5.3% range. The method was applied to the quantitative analysis of 2,5-HD in urine samples from an external Quality Assurance Programme for Organic Solvent Metabolites. Moreover, the metabolites 5-hydroxy-2-hexanone, 2,5-hexanediol and 4,5-dihydroxy-2-hexanone were identified and confirmed in hydrolyzed urine of rats exposed to n-hexane.

Air Ionization↗

Determination of n-hexane metabolites by liquid chromatography/mass spectrometry. 2. Glucuronide-conjugated metabolites in untreated urine samples by electrospray ionization.

A liquid chromatography atmospheric pressure electrospray mass spectrometry (ESI-LC/MS) system was evaluated for the identification and characterization of n-hexane conjugated metabolites (glucuronides) in untreated urine samples. Chromatography of glucuronides was obtained under ion-suppressed reversed-phase conditions, by using high-speed (3 cm, 3 microns) columns and formic acid (2 mM) as modifier in the mobile phase. The mass spectrometer was operated in negative ion (NI) mode. For the first time, four glucuronides were identified by ESI-LC/MS in untreated urine samples of rats exposed to n-hexane: 2-hexanol-glucuronide, 5-hydroxy-2-hexanone-glucuronide, 2,5-hexanediol-glucuronide and 4,5-dihydroxy-2-hexanone-glucuronide. Confirmation of the conjugated metabolites was obtained by LC/MS/MS experiments. Gas chromatography/mass spectrometry (GC/MS) and atmospheric pressure chemical ionization (APCI) LC/MS analyses were performed on the same samples. An integrated approach GC/MS-LC/MS for the semi-quantitative analysis of n-hexane glucuronides, whose standards are not commercially available, is discussed and proposed here. In order to understand the fate of the metabolites during sample pre-treatment, a study about the effects of enzymatic and acid hydrolysis on urine samples was conducted on glucuronides isolated by solid-phase extraction. Combined analyses by GC/MS and LC/MS enabled us to distinguish 'true' n-hexane metabolites from compounds resulting from sample treatment and handling (i.e. enzymatic and acid hydrolysis, extraction and GC injection).

Animals↗

Adverse effects of chronic low level lead exposure on kidney function--a risk group study in children.

BACKGROUND: Children have been considered a risk group for lead (Pb) toxicity, mainly because of neurophysiological or neuro-cognitive deficits following Pb exposure. Blood Pb levels (b-Pb) of 100 microg/l currently have been defined as the lowest adverse effect level. The aim of this study was to compare, with the help of urinary markers, the kidney function of children with b-Pb just above this threshold with that of unexposed children, to assess from a nephrological point of view whether the current threshold is justified and whether children really are a particularly vulnerable risk group in terms of Pb-induced kidney damage. METHODS: In a cross-sectional study, 112 children, either from unexposed areas (controls, n=50) or Pb-contaminated areas (n=62), the latter partly with a known history of elevated b-Pb, were examined. Twenty nine urinary or serum markers mostly related to the function or integrity of specific nephron segments were determined (e.g. filtered plasma proteins, tubular enzymes, tubular antigens, eicosanoids). RESULTS: b-Pb were 39+/-13 microg/l in controls and 133+/-62 microg/l in exposed children. The main findings were increased excretion rates of prostaglandins and thromboxane B2, epidermal growth factor, beta2-microglobulin and Clara cell protein in the exposed children. A relationship between b-Pb and the prevalence of values above the upper reference limits was observed. CONCLUSIONS: With the help of urinary markers, nephron segment-specific effects of chronic low-level Pb exposure could be detected in children. The pattern of effects on glomerular, proximal and distal tubular and interstitial markers was similar to that previously observed in adults. The changes, however, occur at lower b-Pb levels than in adults. The current threshold appears to be justified also from a nephrological point of view, and children can indeed be considered a special risk group.

Biomarkers↗

The assessment of biomarkers to detect nephrotoxicity using an integrated database.

Groups of industrial workers exposed to heavy metals (cadmium, mercury, and lead) or solvents were studied together with corresponding control groups. The cohorts were collected from several European centers (countries). Eighty-one measurements were carried out on urine, blood, and serum samples and the results of these analyses together with questionnaire information on each individual were entered into a central database using the relational database package Rbase. After the completion of the database construction phase, the data were exported in a format suitable for analysis by the statistical package SAS. The potential value of each test as an indicator of nephrotoxicity was then assessed. Rigorous exclusion criteria were applied which resulted in the elimination of some tests and samples from the dataset. The measurable contributions of smoking, gender, metal exposure, and site were either singly or in combination assessed by biomarkers for nephrotoxicity. The parameters measured included three urinary enzymes, six specific proteins, total protein, two extracellular matrix markers, four prostaglandins and anti-GBM antibodies, and beta 2-microglobulin in serum. The most sensitive renal tests included the urinary enzymes N-acetyl-beta-D-glucosaminidase (NAG) and intestinal alkaline phosphatase (IAP), brush border antigens, and urinary low-molecular-weight proteins. Of the newer tests investigated the prostaglandins were the most promising. Different patterns of biomarker excretion were observed following exposure to lead, cadmium, or mercury. The dataset provides a unique repository of data which could provide the basis of an enlarging source of information on normal human reference ranges and on the effects of exposure to toxins and the use of biomarkers for monitoring nephrotoxicity.

Biomarkers↗

Peripheral markers of catecholaminergic dysfunction and symptoms of neurotoxicity among styrene-exposed workers.

AIM: A cross-sectional investigation was carried out to assess possible relations between styrene-induced changes in three peripheral markers of catecholaminergic dysfunction and self-reported symptoms of neurotoxicity. SUBJECTS: Male workers (n = 46) aged 14-60 (mean 29.5) years who had been exposed to styrene for an average of 6 (0.2-29) years were recruited in glassfiber reinforced plastics plants. A control group of 30 blue-collar workers aged 22-52 (mean 35) years and with no history of exposure to chemicals was recruited from local industries. Styrene exposure ranged from 5 to 120 ppm (8 h-TWA), the median level being relatively low (25 ppm, 8 h-TWA). Styrene metabolites, mandelic and phenylglycoxylic acids (MAPGA) in the "next morning" urine spot samples ranged from 32.0 to 931.1 mg/g creatinine (median 186.5). METHODS: Platelet monoamine oxidases B (MAO B) and dopamine beta-hydroxylase (DBH) activities were assessed using methods based on HPLC and electrochemical detection. Plasma prolactin (PRL) was measured by a commercially available immunoassay. Questionnaire 16 (Q16) was used to survey self-reported symptoms. RESULTS: Although there was no difference in DBH activity between exposed workers and controls, the most highly exposed workers had significantly lower activity than control subjects. A tendency to lower platelet MAO B activity in exposed than in control subjects was observed. The prevalence of plasma DBH and platelet MAO B values below the lower reference limit was similar in the two groups. PRL values exceeding the upper reference limit were higher (14/46 vs 2/30) among styrene-exposed workers, who also exhibited significantly higher median levels (10.0 vs 5.7 micrograms/l) than control subjects. Although the number of reported symptoms was similar among exposed and control subjects, in the exposed group it was positively associated with urinary MAPGA (Rho = 0.30, P = 0.04). Of the three peripheral markers of catecholaminergic dysfunction, plasma DBH was the only parameter negatively related to both urinary MAPGA (F = 9.56, P = 0.003) and the number of reported symptoms (Rho = 0.23, P = 0.05). CONCLUSIONS: Plasma PRL appears to be a sensitive marker of styrene-induced tubero-infundibular dopaminergic dysfunction in male subjects. DBH in plasma and MAO B in platelets seem to be less suitable markers for biomonitoring effect at the individual level, although DBH was related to the number of reported symptoms and to internal dose. Further studies on a larger and more exposed population are necessary to clarify the significance of these markers for health and their predictive value with regard to both subjective disturbances and concurrently administered performance tests.

Adolescent↗

Age-related changes in interstitial norepinephrine. A microdialysis study in spontaneously hypertensive rats.

This study was aimed at evaluating the time course of interstitial norepinephrine (NE) concentrations in the white adipose tissue and at assessing NE release after local perfusion with tyramine hydrochloride (TYR) in rats of different ages. Two groups of eight spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats, aged 14 to 16 weeks, were studied. The same animals were reexamined at the age of 52 to 54 weeks. A soft microdialysis probe was implanted subcutaneously in the parascapular region and was perfused with Ringer solution (flow rate: 2.0 microL/min). After an equilibration period, NE levels were monitored for 120 min, following which, TYR (0.1 nmol/min) was perfused for 90 min. Dialysates from each 30 min collection period were analyzed by HPLC using electrochemical detection. At 14 to 16 weeks, SHR showed higher NE concentrations in dialysates as compared to WKY (1124.0 pg/mL v 541.4 pg/mL; P < .001) and a blunted response to TYR challenge. The net output, estimated by subtracting basal values, was 86.0 pg NE/h in SHR as compared to 212.5 pg NE/ h in WKY (P = .005). Differences in basal NE levels persisted in the same aged groups (P < .001) as well as a blunted response to TYR. The net NE output was still lower in SHR as compared to WKY (320.4 pg NE/h v 414.7 pg NE/h in WKY; P = .023). Basal levels of NE in SHR could be accounted for by either a higher amount of the neurotransmitter stored into and released from vescicles or by an increased firing rate of the sympathetic fibers. Since TYR is known to deplete axoplasmic but not vesicular NE available for neurotransmission, the response of SHR to TYR challenge is consistent with an increased turnover rate of NE. Aging was associated with an increased response to TYR in both strains, thus suggesting an age-dependent decline in turnover rates or changes in NE reuptake mechanisms.

Adipose Tissue↗

Renal effects of captopril, indomethacin and nifedipine in nephrotic patients after an oral protein load.

BACKGROUND: In this study we investigated whether the increase in proteinuria induced by an oral protein load may be prevented by the angiotensin-converting enzyme inhibitor (ACEI) captopril in patients with nephrotic syndrome, and whether the effects of captopril on renal haemodynamics and/or glomerular selectivity are comparable to those obtained with the nonsteroidal anti-inflammatory drug (NSAID) indomethacin and the calcium-channel blocker (CaCB) nifedipine. METHODS: Twelve subjects underwent the following treatments: (1) low-protein meal (0.2 g protein/kg body wt), (2) high-protein meal (1.3 g protein/kg body wt), (3) high-protein meal plus oral captopril (50 mg), (4) high-protein meal plus oral nifedipine (10 mg), (5) high-protein meal plus oral indomethacin (50 mg). Urine and blood samples were obtained after meals and tested for total protein, immunoglobulin G and albumin. GFR and renal plasma flow (RPF) were calculated from iothalamate and p-aminohippuric acid clearances respectively. RESULTS: Mean arterial pressure decreased significantly after both captopril (-4%, P = 0.001) and nifedipine (-5%, P = 0.0019). Compared with the low-protein meal, mean values of GFR and RPF increased significantly after the high-protein meal alone (+21%, P = 0.0002; +10%, P = 0.0491 respectively), and after captopril (+18%, P = 0.0025; +24%, P = 0.0034 respectively) or nifedipine administration (+30%, P = 0.0001; +21%, P = 0.0036 respectively), whereas they remained unchanged after the high-protein meal plus indomethacin administration. FF did not change significantly under the five experimental conditions. The increase in urinary protein excretion induced by the meat load (total protein +18%, P = 0.0102; albumin +26%, P = 0.0316; IgG +28%, P = 0.0203) was entirely blocked by both captopril and indomethacin, whereas it was further increased by nifedipine administration. CONCLUSIONS: Both captopril and indomethacin, but not nifedipine, are able to prevent the increase in urinary protein excretion rate following a meat meal. The antiproteinuric effect of captopril is comparable to that of indomethacin, but the renal haemodynamic changes induced by these drugs differ considerably, because the filtration capacity and the renal functional reserve were preserved by captopril and decreased by indomethacin. The reduction in systemic blood pressure following administration of both captopril and nifedipine does not account for changes in proteinuria, since, with a similar degree of blood pressure lowering, urinary protein excretion is reduced by captopril and increased by nifedipine.

Adolescent↗

Development and validation of new screening tests for nephrotoxic effects.

Within the framework of an European Commission-funded project, groups of industrial workers exposed to heavy metals (cadmium, mercury and lead) or solvents were studied together with corresponding control groups. Eighty-one measurements were carried out on urine and serum samples and the scientific results together with individual questionnaire information were entered into a central database. Data obtained was assessed centrally and individually in subsidiary studies. The measurable contributions were assessed either singly or in combination, of smoking, gender, metal exposure and site, to nephrotoxicity. The potential value of each test as an indicator of nephrotoxicity was then assessed on the basis of sensitivity and specificity. A number of new tests including prostaglandins and for extracellular matrix components were investigated as well as established tests for renal damage and dysfunction. The data obtained from this comprehensive study emphasises the value of noninvasive biomarkers for the early detection of nephrotoxicity due to environmental toxins. The urinary profile varied with the type of environmental/occupational toxin. By careful selection of a small panel of markers they can be used to indicate the presence of renal damage, the principal region affected, and to monitor the progress of disease and damage. Biomarkers were also used to confirm and tentatively establish safe exposure levels to nephrotoxins.

Biomarkers↗

Biochemical markers of neurotoxicity. A review of mechanistic studies and applications.

Neurotoxicology presents major challenges to the development of biological markers in accordance to conventional research strategies. Because of the inaccessibility of the nervous system, one of the proposed alternatives is the study of biochemical signals in peripheral tissues which can easily and ethically be obtained in humans, and which could represent surrogate indicators of equivalent parameters in the nervous tissue. Considerable scientific support to this approach is provided by the results of recent investigations in major areas of pharmacology and psychobiology. Studies examining parameters of neurotransmission and second messenger systems in peripheral blood cells, and variations in the peripheral body fluid content of endogenous substances reflecting nervous tissue dysfunction or damage are presented in this paper as examples of efforts toward rational development and validation of novel indicators of nervous system toxicity. Cholinergic muscarinic receptors and calcium signalling in peripheral blood lymphocytes, myelin basic protein in cerebrospinal fluid, and blood polyamines are discussed as potential surrogate indicators based on the results of in vitro or in vivo animal studies of neurotoxic metals (mercury, triethyltin), pesticides (disulfoton), drugs of abuse (d-fenfluramine) and model epileptogenic compounds (kainic acid). Data from investigations examining serum prolactin, type B monoamine oxidase (MAO-B) and dopamine beta-hydroxylase (DBH) in workers occupationally exposed to manganese, lead or styrene are also presented. Although research in this field is still at its very early stage, current evidence suggests that (i) certain neurochemical markers may be valuably used in animal studies as a complement to conventional laboratory tests to augment their sensitivity or predictivity; (ii) a mechanistic research approach is required to establish which markers offer the greatest promise for application in human biomonitoring.

Animals↗

Effects of urinary macromolecules on the nucleation of calcium oxalate in idiopathic stone formers and healthy controls.

Urinary macromolecules have attracted great interest because of their possible role as both promoters and inhibitors of calcium oxalate (CaOx) crystallization and it remains unclear whether there is any difference, in their nucleating activity, between stone formers and controls. We selected 9 male idiopathic CaOx stone formers whose 24-h urines presented no evidence of common urinary stone risk factors such as hypercalciuria, hyperoxaluria, hyperuricosuria, hypocitraturia, hypomagnesiuria or low glycosaminoglycans excretion and 12 male controls (matched for age and body weight) whose 24-h urines did not differ from those of stone formers. The study of urinary CaOx nucleation was made in freshly voided overnight urines whose biochemical composition was almost identical in the two groups. In filtered (0.22 micron) and ultrafiltered (10 kDa) urine we performed an oxalate tolerance test to determine the permissible increment of oxalate, the oxalate level for nucleation and the permissible increment of CaOx relative supersaturation (CaOx RS). In filtered urine from stone formers the permissible increment of oxalate was lower than controls (30 +/- 10.2 vs. 46.7 +/- 9.7 mg/l, P = 0.001), the oxalate level for nucleation was lower (64.4 +/- 14.2 vs. 79.5 +/- 15.6 mg/l, P = 0.035) and the permissible increment of CaOx RS was also lower (9.71 +/- 2.59 vs. 13.39 +/- 3.62, P = 0.018). In ultrafiltered urine these differences disappeared because the removal of macromolecules in stone formers significantly enhanced the oxalate-tolerance values. The difference between the change of the oxalate permissible increment of filtered and ultrafiltered urine allowed a distinction to be made between stone formers and controls that was not feasible in other ways (7.6 +/- 5.3 vs. 3.3 +/- 5.9 mg/l, P < 0.0001). The study suggests that, in idiopathic CaOx stone formers free from common urinary risk factors of CaOx crystallization, there is an increased tendency for CaOx nucleation in urine, which is mediated by macromolecular components.

Adult↗

Immunological changes among workers occupationally exposed to styrene.

The functional status of the immune system was investigated in a group of 71 workers exposed to styrene and in 65 control subjects, recruited according to the same selection criteria and comparable as to sex, age, and confounding variables. Air and biological monitoring were used to characterize styrene exposure (median of the main urinary metabolites in the "next-morning" spot samples: 106 mg/g creatinine). Phenotypic analysis of peripheral blood lymphocytes (PBL) by automated flow cytometry revealed a reduced proportion of T lymphocyte subsets (CD3+, CD4+ and CD4+45+), with no changes in CD8+, and a higher proportion of B lymphocytes (CD19+) among styrene-exposed workers. The exposed workers showed a higher proportion of activation markers, namely DR and interleukin-2 receptors (CD25). Immunoglobulin subclasses were comparable in the two groups. An increased prevalence of abnormally low values was apparent for CD2+, CD3+, CD4+, CD4+45+ and CD11b subsets among workers exposed to styrene, whereas CD19+, DR+ and CD25+ showed an increased prevalence of abnormally high values. Natural killer-related phenotypes (CD56+, CD56+16+, and CD56+16-) were more expressed among styrene workers, with average increase of 30%. However, the frequency distribution of the lytic activity of natural killer cells against K-562 target cells was shifted towards lower values in the exposed workers as compared to control subjects. Dose-response relationships between indices of internal dose and prevalence of abnormal values were detectable for T lymphocyte subsets, NK phenotypes, and activation markers. These findings suggest that moderate exposure to styrene is associated with an altered distribution of lymphocyte subsets.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Use of intermediate end-points to prevent long-term outcomes.

Biomarkers may be very useful to assess and control the risk of long-term outcomes associated with exposure to industrial chemicals. Even when dose-effect and dose-response relationships have been demonstrated, the process of standard setting and the definition of 'safe' exposure levels is hampered by: (i) the arbitrary nature of attempts to distinguish acceptable from unacceptable effects; (ii) the difficulties in assessing the prognostic value of observed changes; (iii) the influence of the study power on statistically defined thresholds. Integration of epidemiological findings with mechanistic studies is necessary to assure confidence in risk assessment and to undertake sound risk management.

Animals↗

Monitoring norepinephrine levels by microdialysis in the white adipose tissue of spontaneously hypertensive rats.

1. To investigate whether microdialysis is suitable to monitor catecholamine in white adipose tissue of conscious rat and to assess eventual differences in norepinephrine (NE) interstitial levels, two groups of 12 male spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats, 14-16 weeks old, were compared. 2. A flexible microdialysis probe was implanted subcutaneously in the parascapular region, and perfused with Ringer solution (flow rate: 2.0 mu L/min). After a 20 min equilibration period, NE levels were monitored over a 120 min period; then, tyramine hydrochloride (0.1 nmol/min) was perfused for 80 min. Dialysates from each 20 min collection period were analysed by HPLC with electrochemical detection for NE. 3. Basal levels of NE (adjusted for the recovery) were higher in SHR compared to WKY (1210.0 +/- 140.5 pg/mL dialysate vs 573.3 +/- 75.8 pg/mL dialysate; P < 0.001, ANOVA). In both strains tyramine perfusion increased NE concentration in dialysates; the net (i.e. baseline subtracted) NE output was lower (76.3 pg/h, s.e.m. 22.3) in SHR compared with that shown by WKY rats (201.0 pg/h, s.e.m 18.4, P < 0.01). 4. The increased basal levels of NE observed in SHR are associated with a blunted response to tyramine challenge. Since tyramine is known to cause NE release from the cytosol but not from vesicle stores, such a blunted response is consistent with an increased turnover rate of NE or with an accelerated uptake in pre-synaptic vesicles which, together with the higher basal levels, would suggest increased noradrenergic activity.

Adipose Tissue↗

Monitoring of exposure to methylpentanes by diffusive sampling and urine analysis for alcoholic metabolites.

OBJECTIVES: To investigate the possibilities of personal ambient monitoring and biological monitoring for methylpentane isomers. METHODS: The performance of activated carbon cloth to absorb 2- and 3-methylpentane was studied by experimental vapour exposure followed by solvent extraction and gas chromatography (GC). Urine from workers and rats exposed to 2- and 3-methylpentane was analysed by GC with or without acid or enzymatic hydrolysis. RESULTS: Carbon cloth absorbed 2- and 3-methylpentane linearly to exposures up to eight hours and to 400 ppm, and was sensitive enough to detect a 15 minute peak of exposure. The two isomers were clearly separated from hexane on a DB-1 column. For analysis of the urine, enzymatic hydrolysis was superior to acid hydrolysis. Exposure of rats to methylpentane vapours showed that 2-methyl-2-pentanol and 3-methyl-2-pentanol were excreted in urine in proportion to the dose of 2-methylpentane and 3-methylpentane, respectively. 2-Methyl derivatives of 1-, 3-, and 4-propanol, 2-methylpentane-2,4-diol, and 3-methyl-2-pentanol were minor metabolites. Analysis of urine from the exposed workers showed that 2-methyl- and 3-methyl-2-pentanol are leading urinary metabolites after exposure to the corresponding methylpentane. CONCLUSIONS: Diffusive sampling is applicable to monitor 2- and 3-methylpentane vapours as is the case for hexane vapour. 2-Methyl-2-pentanol and 3-methyl-2-pentanol will be markers of occupational exposure to 2-methylpentane and 3-methylpentane, respectively. Also, 2-methylpentane-2,4-diol might be a marker of exposure to 2-methylpentane.

Animals↗

Neurobehavioral effects of manganese in workers from a ferroalloy plant after temporary cessation of exposure.

OBJECTIVES: The goal of this study was to assess long-term neurobehavioral effects associated with low airborne concentrations of manganese in a ferroalloy plant. METHODS: During a period of forced cessation of work (1 to 42 d) neurobehavioral performance on tests of simple reaction time, finger tapping, digit span, additions, symbol digit, and shapes comparison was evaluated for 58 workers exposed from 1 to 28 (mean 13, SD 7) years to manganese. Airborne manganese concentrations in total dust had been reduced in the last 10 years from 70-159 micrograms x m-3 (geometric means in different areas) to 27-270 micrograms x m-3. For each worker, manganese concentrations in blood and urine were measured, and a cumulative exposure index was also calculated. RESULTS: Blood manganese and urinary manganese ranged from 4 to 18 micrograms x 1-1 (0.07 to 0.03 mumol x 1-1) and from 0.7 to 7 micrograms x 1-1 (0.01 to 0.13 mumol x 1-1) respectively. Significant relationships were found between the blood manganese and urinary manganese levels and between these biological measures and the cumulative exposure index. Correlations were also found between the blood manganese level, the urinary manganese level, and the cumulative exposure index and the following tests: finger tapping, symbol digit, digit span, and additions. The correlation coefficients increased as the latency time after the cessation of exposure and work seniority increased. CONCLUSIONS: The results support the hypothesis that the neurobehavioral effects observed at exposure levels well below current occupational standards are related to manganese body burden, which is better reflected by the blood manganese level after the cessation of exposure.

Adult↗