Neurobehavioral Test Battery Research Articles

Intrauterine environment-genome interaction and Children's development (2): Brain structure impairment and behavioral disturbance induced in male mice offspring by a single intraperitoneal administration of domoic acid (DA) to their dams

To demonstrate induction of delayed central nervous toxicity by disturbing neuronal activities in the developing brain, we administered a single intraperitoneal dose of domoic acid (DA; 1 mg/kg), a potent glutamate receptor agonist, to pregnant female mice at the gestational day of 11.5, 14.5 or 17.5. The dams had recovered from acute symptoms within 24 hr, followed by normal delivery, feeding and weaning. All male offspring mice after weaning were apparently normal in response to handlers during cage maintenance, body weight measurement and to mate mice in group housing conditions. At the age of 11 weeks, our neurobehavior testing battery revealed severe impairment of learning and memory with serious deviances of anxiety-related behaviors. The developed brain of prenatally exposed mice showed myelination failure and the overgrowth of neuronal processes of the limbic cortex neurons. This study indicates that the temporal disturbance of neurotransmission of the developing brain induces irreversible structural and functional damage to offspring which becomes monitorable in their adulthood by a proper battery of neurobehavioral tests.

Effect of heavy metals exposure on neurobehavioral function in welders

To explore the relationship between heavy metals exposure and neurobehavioral function impairment in welders. The metals exposure in 82 welders and 51 operators were investigated with blood Pb, Cd and Mn via AAS, and the nervous impairment was evaluated with neurobehavioral core test battery (NCTB). Pb [(115.49 +/- 79.22) microg/L] and Cd [(3.67 +/- 3.19) microg/L] in welders were significantly higher than operators [(69.32 +/- 50.79) and (0.83 +/- 0.76) microg/L respectively] (P < 0.05). Welders had worse standard scores of NCTB 13 items such as depression-dejection than non-welders (P < 0.05). Significant difference of confusion-bewilderment and forward digit span in welders only existed in different groups of Pb and Mn, respectively. A dose-effect relationship was found between forward digit span and serum Mn level in welders. General linear regression analysis indicated that Pb exposure, Mn exposure and alcohol consume had negative relation with the loss of nervous system function. The nervous impairment in welders is attributed to occupational exposure to Pb and Mn, concomitantly.

Effects of occupational pesticide exposure on children applying pesticides

Nearly 40% of the Egyptian workforce is employed in agriculture. The cotton industry relies on children and adolescents, who work seasonally, to apply pesticides to the cotton crops. Although previous research has examined adult pesticide exposures in this workforce in Egypt, no research has examined the health effects in adolescents. This study attempts to systematically replicate findings examining the impact of organophosphate pesticide (OP) exposure in adults on Arabic speaking children working as applicators. The aim of this study was to examine the impact of pesticide exposure on children and adolescents spraying cotton fields. Male children currently applying pesticides between the ages of 9 and 15 (Younger, n = 30) and 16 and 19 (Older, n = 20) were recruited for the study. They completed a neurobehavioral test battery; personality inventory; work, health, and exposure questionnaires; and medical and neurological screening exams. Blood samples were collected to measure acetylcholinesterase. Children not working in agriculture, matched on age and education, served as controls. Both Younger and Older applicator groups, performed significantly worse than the controls on the majority of neurobehavioral tests controlling for age and years of education. The applicators reported significantly more neurological symptoms than the controls and had lower acetylcholinesterase activity. A dose–effect relationship demonstrated that increased years of exposure to organophosphate pesticides is associated with cognitive deficits. This is one of the several studies demonstrating that functional cognitive effects are positively correlated with increased years of exposure to OP pesticides, though primarily in adult populations, building confidence in the association. Since children around the world are exposed to OP pesticides, these studies suggest that the need to evaluate this potential problem is urgent.

Characteristic of the neurobehavioral functional changes in coke oven workers

To explore the effect of polycyclic aromatic hydrocarbons on the neurobehavioral function of coke oven workers. 200 healthy adult male coke oven workers were selected from a coke plant of a state-owned steel enterprise in Taiyuan City. 88 controls occupationally unexposed to polycyclic aromatic hydrocarbons (PAHs) were selected from the same enterprise. All the subjects participated in this investigation voluntarily in their consent. Concentration of B(a)P in the working environment was monitored by High Performance Liquid Chromatography (HPLC). Urine samples were sampled immediately after working shifts. The level of urinary 1-hydroxypyrene was determined by HPLC. General information of workers correlated with the investigation was collected in a questionnaire according to the same criteria by well-trained investigators. Neurobehavioral core test battery (NCTB) recommended WHO was performed on coke oven workers and controls to test the neurobehavioral changes and the mood state. the concentration of B(a)P at oven bottom,oven side and oven top were 0.0195 microg/m3, 0.186 microg/m3 and 1.624 microg/m3 respectively, that at oven side and oven top being higher than the one stipulated by the occupational hygiene criterion. Urinary 1-hydroxypyrene was significantly different between the exposure group (3.42 +/- 0.98 micromol/mol creatinine) and control group (2.75 +/- 1.09 micromol/mol creatinine). No significant differences were found between exposure group and control group of age, working years, smoking, drinking and unhealthy food consumption; however, compared to the controls, the scores of total digital span, the forward digital span, and right dotting in the coke oven workers were lower, but that of total dotting was higher, with a statistical significance. According to urinary 1-hydroxypyrene concentration, all the subjects were divided into three groups. (<3.10 micromol/mol creatinine, 3.10 micromol/mol creatinine, >3.87 micromol/mol creatinine). Significant differences of the total digital span, the forward digital span, backward digital span, digit symbol and Benton visual retentions existed in different urinary 1-hydroxypyrene concentration groups and showed a dose-response tendency. Results of multiple stepwise regression analysis and correlation analysis showed that the level of urinary 1-hydroxypyrene affected memory and perception of coke oven workers and negative correlations between the level of urinary 1-hydroxypyrene and changes in neurobehavioral function were found. PAHs mainly causes decrease of memory and perception in coke oven workers.

REPEAT TEST SCORES ON NEUROBEHAVIORAL MEASURES OVER AN EIGHT-YEAR PERIOD IN A SAMPLE OF PORTUGUESE CHILDREN

Normative data were collected on a sample of 503 Portuguese children who were taking part in a dental study. At the outset, the children were aged 8–11.9 years, with an average of just over 10. A standard battery of neurobehavioral tests covering learning and memory, visual-motor function, and attention was administered at baseline and during seven subsequent years. Normative test data are presented separately by gender and by age at study inception (younger versus older). Results provide normative data for use in clinical settings, where dissociations in performance between cognitive domains need to be identified for diagnostic and therapeutic purposes.

A neurobehavioral study of current and former welders exposed to manganese

Neurobehavioral functions were studied in 96 welders currently exposed to the geometric mean (GM) concentration of 121 μg/m 3 (range 7–2322) manganese (Mn) in welding fume (air-Mn) based on the individual mean from two successive days of sampling. They were compared to 96 age-matched referents. The arithmetic mean (AM) concentration of Mn in whole blood (B-Mn) was 8.6 μg/L versus 6.9 μg/L in the referents. Associations between the Digit Symbol and Finger Tapping test scores and B-Mn and air-Mn, respectively, were observed. The welders exposed to the highest air-Mn concentrations (GM 423 μg/m 3 range 204–2322) had statistically significantly poorer Finger Tapping test score as compared to their age-matched referents. The welders with the highest AM concentration of B-Mn (12.6 μg/L) scored statistically significantly poorer on the Digit Symbol test when compared to the age-matched referents (AM B-Mn 7.5 μg/L). The same neurobehavioral test battery was applied to 27 patients diagnosed, and financially compensated, as having welding related manganism. They were on average 44.9 (range 34–51) years old at the time of diagnosis, which on average was 5.8 years prior to this study. They had worked as welders for 23.1 years on average (range 15–30). The most affected neurobehavioral functions were associated with impaired Finger Tapping speed and Grooved Pegboard performance. The patients had no alterations in hand tremor as assessed by the CATSYS system, while a few subjects had noticeable tremor as assessed by the Static Steadiness test.

An Ecosystem Health Approach and Children's Health Living in the Vicinity of Banana Plantations

ISEE-757 Objective: To study children's pesticide exposure, its health effects and social consequences in agricultural communities. Materials and Methods: The study population included 3 communities nearby banana (multinational) and plantain (small-scale peasants) plantations with extensive pesticide use, and 2 with low pesticide use (cattle and organic farmers). Pesticide exposure pathways in children were studied both qualitatively and quantitatively within a social, cultural, and gender context. To study perceptions of pesticide risks, focus groups were held in parents and semistructured interviews were performed in key-actors. Exposure was assessed quantitatively by measuring pesticides metabolites in urine in 55 exposed and 12 low-exposed 7- and 8-year-old children. In 14 of these children dermal exposure was assessed, and dust samples were taken from their homes. In addition, environmental samples were taken (air, surface and drinking water, soil). To study children's development and health, a neurobehavioral test-battery was performed in all 7- and 8-year-old children of the 5 communities. Results: Pesticide exposure pathways and patterns differed for children living in banana communities as compared to small-scale plantain communities. Male and female small-scale farmers take their children to the field as a cultural habit, resulting in incidentally high exposures. Yet, in the banana communities children are constantly being exposed due to living very nearby the plantations. For example, weekly aerial spraying of fungicides results in a drift of small droplets directly entering school and the most nearby houses. Perceptions of pesticide risks differed between communities, and between fathers and mothers, but principally between working parents (emphasizing utility) and housewives (emphasizing risks). Quantitative exposure pathways and the relation between exposure and health effects in the children are currently being analyzed. Conclusions: Our results identify environmental pesticide exposure and children's health; agricultural, social, and cultural practices; and gender-dependent variables influencing in both exposure and health.

Model studies for evaluating the neurobehavioral effects of complex hydrocarbon solvents: II. Neurobehavioral effects of white spirit in rat and human

To evaluate the neurobehavioral effects of hydrocarbon solvents and to establish a working model for extrapolating animal test data to humans, studies were conducted which involved inhalation exposure of rats and humans to white spirit (WS). The specific objectives of these studies were to evaluate the behavioral effects of exposure to WS in rats and humans and to determine relationships between internal levels of exposure and behavioral effects. In both animals and volunteers, methods for assessment of similar functional effects were used to enable interspecies comparisons. A battery of tests including standardized observational measures, spontaneous motor activity assessments and learned visual discrimination performance was utilized in rat studies to evaluate acute central nervous system (CNS) depression. Groups of rats were exposed to WS at target concentrations of 0, 600, 2400 or 4800 mg/m 3, 8 h/day for 3 consecutive days. Blood and brain concentrations of two WS constituents; 1,2,4-trimethylbenzene (TMB) and n-decane (NDEC), were used as biomarkers of internal exposure. In a volunteer study, 12 healthy male subjects were exposed for 4 h to either 57 or 570 mg/m 3 WS in two test sessions spaced 7 days apart, and neurobehavioral effects were measured using a computerized neurobehavioral test battery. Blood samples were taken at the end of the exposure period to measure internal concentrations of TMB and NDEC. Results of the behavioral tests in rats indicated WS-induced changes particularly in performance and learned behavior. In humans, some subtle performance deficits were observed, particularly in attention. The behavioral effects were related to concentrations of the WS components in the central nervous system. These studies demonstrated a qualitative similarity in response between rats and humans, adding support to the view that the rodent tests can be used to predict levels of response in humans and to assist in setting occupational exposure levels for hydrocarbon solvents.

Neurobehavioral Performance of Adult and Adolescent Agricultural Workers

There are many occupational hazards associated with working in agriculture including risk of injury and exposure to pesticides. Research examining neurobehavioral effects of pesticide exposure have focused primarily on the acute effects in adults working in agriculture. Organophosphate poisoned populations have shown a consistent pattern of deficits when compared to a non-exposed or non-poisoned population on measures of motor speed and coordination, sustained attention, and information processing speed. Fewer studies have examined the effect of long-term low-level exposure on nervous system functioning in agricultural workers. Pesticides are thought to pose a considerably higher risk to children than to adults, yet little is known about the extent or magnitude of health problems related to occupational exposure to pesticides in children and adolescents. The present study compared the neurobehavioral performance of adolescents and adults working in agriculture and examined the impact of years working in agriculture on neurobehavioral performance. One hundred seventy-five Hispanic adolescent and adults completed a neurobehavioral test battery consisting of 10 computer-based tests measuring attention, response speed, coordination and memory. Age, gender, school experience, and years working in agriculture all impacted performance on the neurobehavioral tests. Comparison of adult and adolescents did not reveal decreased neurobehavioral performance in adolescents. On several tests the adolescents performed better than adult counterparts. The adolescents and adults were engaged in comparable agricultural working environments at the time of the neurobehavioral testing. These findings suggest that, at the time of exposure to pesticides, adolescents are not more vulnerable to the effects of working in agriculture. Evidence from this study suggests that cumulative exposure to low levels of pesticides over many years of agricultural work is associated with neurological impairment as measured by the Selective Attention, Symbol-Digit, Reaction Time tests. Experience handling pesticides was also associated with deficits in neurobehavioral performance.

Neurobehavioral effects among inhabitants around mobile phone base stations

Background There is a general concern on the possible hazardous health effects of exposure to radiofrequency electromagnetic radiations (RFR) emitted from mobile phone base station antennas on the human nervous system. Aim To identify the possible neurobehavioral deficits among inhabitants living nearby mobile phone base stations. Methods A cross-sectional study was conducted on (85) inhabitants living nearby the first mobile phone station antenna in Menoufiya governorate, Egypt, 37 are living in a building under the station antenna while 48 opposite the station. A control group (80) participants were matched with the exposed for age, sex, occupation and educational level. All participants completed a structured questionnaire containing: personal, educational and medical histories; general and neurological examinations; neurobehavioral test battery (NBTB) [involving tests for visuomotor speed, problem solving, attention and memory]; in addition to Eysenck personality questionnaire (EPQ). Results The prevalence of neuropsychiatric complaints as headache (23.5%), memory changes (28.2%), dizziness (18.8%), tremors (9.4%), depressive symptoms (21.7%), and sleep disturbance (23.5%) were significantly higher among exposed inhabitants than controls: (10%), (5%), (5%), (0%), (8.8%) and (10%), respectively ( P < 0.05). The NBTB indicated that the exposed inhabitants exhibited a significantly lower performance than controls in one of the tests of attention and short-term auditory memory [Paced Auditory Serial Addition Test (PASAT)]. Also, the inhabitants opposite the station exhibited a lower performance in the problem solving test (block design) than those under the station. All inhabitants exhibited a better performance in the two tests of visuomotor speed (Digit symbol and Trailmaking B) and one test of attention (Trailmaking A) than controls. The last available measures of RFR emitted from the first mobile phone base station antennas in Menoufiya governorate were less than the allowable standard level. Conclusions and recommendations Inhabitants living nearby mobile phone base stations are at risk for developing neuropsychiatric problems and some changes in the performance of neurobehavioral functions either by facilitation or inhibition. So, revision of standard guidelines for public exposure to RER from mobile phone base station antennas and using of NBTB for regular assessment and early detection of biological effects among inhabitants around the stations are recommended.

Model studies for evaluating the acute neurobehavioral effects of complex hydrocarbon solvents: I. Validation of methods with ethanol

As a preliminary step to evaluating the acute neurobehavioral effects of hydrocarbon solvents and to establish a working model for extrapolating animal test data to humans, joint neurobehavioral/toxicokinetic studies were conducted which involved administering ethanol to rats and volunteers. The specific objectives of the present studies were to evaluate the acute central nervous system (CNS) effects of ethanol in rats and humans and to assess relationships between internal levels of exposure and behavioral effects. A more general objective was to validate a battery of neurobehavioral tests that could be used to carry out comparative studies in both species. Accordingly, a range of tests including standardized observational measures, spontaneous motor activity assessments and learned visual discrimination performance was utilized in rat studies to evaluate acute CNS effects. Groups of rats were given ethanol at levels of approximately 0.5, 1.0 or 2.0 g/kg, with blood level measurements to verify internal doses. In a volunteer study, 12 healthy male subjects were given 0.65 g/kg ethanol, a level approximating the limit for motor vehicle operation in The Netherlands, and neurobehavioral effects were measured prior to and 1 and 3 h after ethanol administration, with a computerized neurobehavioral test battery. Blood and air measurements were made to quantify internal doses. Results of the behavioral tests in rats provided evidence of ethanol-induced changes in neuromuscular, sensori-motor, and activity domains. There were also significant changes in visual discrimination, particularly in the areas of general measures of responding and psychomotor speed. In humans there were small but statistically significant effects on learning and memory, psychomotor skills and attention. However, the effects were subtle and not all parameters within given domains were affected. These studies demonstrated a qualitative similarity in response between rats and humans.

Our recent experiences with sarin poisoning cases in Japan and pesticide users with references to some selected chemicals

Attention has been paid to neurobehavioral effects of occupational and environmental exposures to chemicals such as pesticides, heavy metals and organic solvents. The area of research that includes neurobehavioral methods and effects in occupational and environmental health has been called “Occupational and Environmental Neurology and Behavioral Medicine.” The methods, by which early changes in neurological, cognitive and behavioral function can be assessed, include neurobehavioral test battery, neurophysiological methods, questionnaires and structured interview, biochemical markers and imaging techniques. The author presents his observations of neurobehavioral and neurophysiological effects in Tokyo subway sarin poisoning cases as well as in pesticide users (tobacco farmers) in Malaysia in relation to Green Tobacco Sickness (GTS). In sarin cases, a variety effects were observed 6–8 months after exposure, suggesting delayed neurological effects. Studies on pesticide users revealed that organophosphorus and dithiocarbamate affected peripheral nerve conduction and postural balance; subjective symptoms related to GTS were also observed, indicating the effects of nicotine absorbed from wet tobacco leaves. In addition, non-neurological effects of pesticides and other chemicals are presented, in relation to genetic polymorphism and oxidative stress.

Developing methods for assessing neurotoxic effects in Hispanic non-English speaking children

Many factors affect the growth and development of children, including chemicals in the environment. Children have greater exposure to toxicants than adults due to both behavior and their increased food: body-mass ratio. Furthermore, the developing brain and organ systems of infants and children and their immature metabolism also make them more vulnerable to environmental toxins. Children from all cultures and backgrounds are at risk. However, minorities may be at greatest risk. In order to evaluate the impact of environmental exposures on neurodevelopment it is necessary to have effective methods that will allow accurate conclusions to be drawn. We have developed a battery to assess neurobehavioral performance in non-English speaking Hispanic children ages 4 years and older. This paper will examine the associations between age and performance and present test–retest correlations. Two hundred and forty one Hispanic children between the ages of 4 and 9 years completed a neurobehavioral test battery twice, approximately 1 month apart. The battery consists of computerized tests from the Behavioral Assessment and Research System, tests selected from the Pediatric Environmental Neurobehavioral Test Battery, and the Object Memory Test. Multiple regression was used to examine the association between age, gender and mother's education on performance. All of the tests, except for Continuous Performance, showed that performance improved as the child gets older. Gender differences were found on several tests with females generally performing worse than males. Correlation coefficients on performance retest measures ranged from .51 to .88. This study has demonstrated the utility of using this test battery to assess cognitive and motor performance in non-English speaking Hispanic children. Tests in the battery assess a range of functions and the measures are sensitive to differences in ages. Test–retest correlations show the reliability of the battery. These support the use of this battery in both cross-sectional and longitudinal studies.

The Effect of Occupational Exposure to Metals on the Nervous System Function in Welders

We explored the relationship between metals exposure and nervous impairment in welders. The metals exposure of 82 welders and 51 operators were evaluated for blood Pb, Cd and Mn by atomic absorption spectrometry, and the nervous system impairment was evaluated with the neurobehavioral core test battery and electromyography. Pb (geometric mean: 117.31 mug/L; range: 0.5-327.6 mug/L) and Cd (geometric mean: 3.54 mug/L; range: 0.2-12.5 mug/L) in welders were significantly higher than those in operators. Welders had higher prevalence of nervous system symptoms and worse standard scores of 8 items such as depression-dejection than operators. Significant difference of nervous performance in welders only existed in different concentration groups of Pb and Mn. The performances of fatigue-inertia and some others had negative correlations with Pb and digit span with Mn. Therefore, the nervous system impairment in welders could be attributed to occupational exposure of Pb and Mn, but not Cd, concomitantly.

Acute neurobehavioral effects of exposure to static magnetic fields: Analyses of exposure–response relations

To assess exposure-response relations between exposure to magnetic fields and neurobehavioral effects. Twenty company volunteers completed a neurobehavioral test battery after they moved their heads with the magnetic field absent, and while they moved their heads in the inhomogenous stray fields of 1.5 and 3.0 T MRI magnets. The value of the stray fields at the position of the head of the volunteer was estimated to be 0.6 T and 1.0 T on the 1.5 T and 3.0 T systems, respectively. Exposure-response relations were found for visual (-2.1%/100 mT) and auditory (-1.0%/100 mT) working memory, eye-hand coordination speed (-1.0%/100 mT), and visual tracking tasks (-3.1%/100 mT). Eye-hand precision, scanning speed, and visual contrast sensitivity were apparently not influenced by the magnetic field strength. Additional research should focus on the potential side effects of interventional MR procedures because of the exposure to strong magnetic fields of these systems.

A comprehensive study on neurobehavior, neurotransmitters and lymphocyte subsets alteration of Chinese manganese welding workers

The neurotoxicity of manganese has been demonstrated by many researches. But few reports have been found on its immunotoxicity in manganese-exposed workers. Here we selected welding workers (aged 34 years) as Mn-exposed subjects. They have been exposed to manganese for 16 years. The control group was from a flour plant. The average concentrations of Mn, Cd, Fe and Ni in work place were 138.40 ± 11.60 μg/m 3, 581.40 ± 45.32 μg/m 3, 3.84 ± 0.53 μg/m 3 and 12.64 ± 2.80 ng/m 3, respectively. Blood Mn (4.84 μg/dl) of welding workers was higher than that of the control group (1.92 μg/dl). Neurobehavioral core test battery (NCTB) recommended by WHO was conducted on the subjects and found that the scores of negative emotions, such as confusion–bewilderment, depression–dejection, fatigue–inertia, and tension–anxiety, were higher in welding workers. Visual simple reaction time and the fast simple reaction time were shorter than that of the control group. The numbers of digital span, forward digital span, backward digital span and digital symbol decreased in welding workers compared with control group. Monoamine neurotransmitters and their metabolism substances in urine were tested by HPLC–ultraviolet. NE, E, MHPG, HVA, DA, DOPAC and 5-HT in the urine of Mn-exposed group had no significant changes while 5-HIAA in Mn-exposed group had significantly decreased compared with that of the control group. Lymphocyte subsets of the subjects were determined by Flow Cytometer. CD3 + T cell, CD4 +CD8 − T cell, CD4 −CD8 + T cell, CD4 +CD45RO − “virgin” lymphocytes, CD4 +CD45RO + “memory” lymphocytes, and CD3 −CD19 + B cell had no significant changes compared with the control group. The results showed that long-term exposure to manganese in welding might have adverse effects on mood state, neurobehavior, and peripheral neurotransmitters. However, they had no effects on lymphocyte subsets parameters.

The Nervous System Effects of Occupational Exposure to Manganese – Measured as Respirable Dust – in a South African Manganese Smelter

Objectives A major recent review of occupational exposure limits for manganese (Mn) has proposed a respirable dust level of 0.1 mg/m 3. There is, however, no theoretical basis for using this exposure metric to estimate the systemic effects of Mn, and little in the way of empirical data relating respirable Mn to neurobehavioural and other non-pulmonary effects. Cross-sectional data from a study showing few and unconvincing neurobehavioural effects of inhalable dust in Mn smelter workers published just prior to this review were reanalyzed here using respirable Mn. The hypotheses tested were that respirable Mn exposure is a more appropriate predictor of neurobehavioural effects than inhalable Mn where such effects exist, and that there should be no observed effects at respirable dust levels below 0.1 mg/m 3. Methods Five hundred and nine production workers and 67 external referents were studied. Exposure measures from personal sampling included the Mn content of respirable dust as a concentration–time integrated cumulative exposure index (CEI) and as average intensity (INT) over a working lifetime. Neurobehavioural endpoints included items from the Swedish nervous system questionnaire (Q16), World Health Organisation neurobehavioural core test battery (WHO NCTB), Swedish performance evaluation system (SPES), Luria–Nebraska (LN), and Danish Product Development (DPD) test batteries, and a brief clinical examination. Results The median respirable Mn exposure was 0.058 mg/m 3 (range = 0–0.51; IQR = 0.02–0.16) amongst the exposed, with 30% having average intensities above the proposed 0.1 mg/m 3 and 44% above the proposed supplemental limit of 0.5 mg/m 3 inhalable dust. As in the study of inhalable Mn effects, there were few respirable Mn effects showing clear continuity of response with increasing exposure. Conclusion These data did not provide empirical support for a respirable, as opposed to an inhalable, dust metric being more sensitive in the identification of Mn effects. Neither metric showed convincing effects within the exposure range studied. Further study is needed to determine a threshold for respirable Mn effects, if such exist, and to verify our findings.

Functional observational battery and motor activity in rats after single administration of two NHE 1 inhibitors

Two tests, a functional observational battery (FOB) and measurement of motor activity, have been used to screen the two NHE inhibitors EMD 96785 and EMD 125021 for neurobehavioral effects. These two NHE inhibitors, which exhibit a marked selectivity for the NHE 1 isoform, are under development in the research laboratories of Merck KGaA. NHE inhibitors are developed for the treatment of acute myocardial infarction and chronic heart failure. In prior studies with EMD 96785 and EMD 125021, clinical symptoms, such as uncoordinated movements and weakness of the hindlimbs, were detected in rats. The aim of this study was the evaluation of clinical findings in more detail using a FOB and measurement of motor activity in 96 female rats. The time course and reversibility of the adverse effects were investigated. The animals were treated with EMD 96785 or EMD 125021 by intravenous injection at a single dose of 100 mg/kg and four different time points (2 h, 1 day, 7 days and 21 days after treatment) were chosen for the clinical examination. This neurobehavioral test battery clearly detected neurological activity and defined time-course characteristics after treatment with EMD 96785 or EMD 125021. The various clinical parameters were grouped into functional-related domains and most alterations were seen in the domains of central nervous system and neuromuscular system. The most prominent clinical findings were seen with the pharmacologically more potent NHE inhibitor EMD 125021 when compared to EMD 96785. The clinical symptoms were proven to be reversible by 7 days after the single treatment for both compounds.

Pallidal index on MRI as a target organ dose of manganese: Structural equation model analysis

We have used a structural equation model (SEM) to analyze the interrelationships among exposure markers, magnetic resonance imaging (MRI) signal index, and neurobehavioral effects. Based on exposure groups, we assessed blood manganese, MRI measurements of pallidal index (PI), and neurobehavioral core test battery (WHO-NCTB) on 111 male workers occupationally exposed to manganese, including welders, smelter workers, and welding rod manufacturing workers. Latent variables were constructed to represent the neurobehavioral effects in an integrated way. The structural equation model revealed that airborne manganese and blood manganese contribute to PI significantly. Manganese exposure in the ambient air may lead to an increase in the internal dose, not only indirectly, by increasing blood manganese level, but also directly, independent of blood concentration. PI significantly contributed to a decrease in neurobehavioral test scores. We found that airborne manganese contributed to PI, and that PI is the most effective predictor of neurobehavioral performance, after adjusting for age and level of education. In conclusion, PI on MRI reflects target organ dose of occupational manganese exposure.

Neurobehavioral performance in workers exposed to toluene

Toluene is widely used in adhesive, printing, painting and petroleum industries in many countries. This study was conducted to examine the effect of chronic exposure to toluene below 100 ppm on neurobehavioral performance using a computerized neurobehavioral test battery that emphasizes simple instructions and practice prior to testing. The Behavioral Assessment and Research System (BARS) with Korean language instructions was administered to 54 workers from three different industries: oil refinery, gravure printing, and rubber boat manufacturing. The battery consisted of the following tests: Digit Span (DS), Simple Reaction Time (SRT), Selective Attention (SAT), Finger Tapping (FT), and Symbol Digit (SD). Urine was collected at the end-of-shift to analyze urinary hippuric acid to assess exposure level to toluene. Based on the previous air toluene level, workers were divided into three groups: Low (21 workers, less than 10 ppm), Moderate (13 workers, 20–30 ppm) and High (20 workers, 70–80 ppm) exposure status. Analysis of Covariance (ANCOVA) adjusting for age, education and work duration as covariates, was performed to examine the relationship between the neurobehavioral performance and the exposure groups. Poorer performance of the High exposure group was found on FT-preferred ( F = 7.034, p = 0.002) and SAT latency ( F = 11.710, p = 0.000). Age showed a significant correlation with SD ( r = 0.417, p = 0.002) and SAT number correct ( r = −0.460, p = 0.000). Years of education and work duration were not significantly correlated with any items. This study supports that toluene exposure below 100 ppm is associated with neurobehavioral changes and that high-level toluene exposure could cause not only attention and concentration, but also motor performance deficits.