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Biomedical subjects

G Winneke

Publications and source records attributed to G Winneke.

At least 73 records · Page 4Linked to original sources

Lead in deciduous teeth of children living in a non-ferrous smelter area and a rural area of the FRG.

Lead concentrations were measured in the deciduous teeth (incisors) of 302 children living in a lead-smelter area in the FRG (Stolberg, Rheinland) and of 86 children living in a nonpolluted rural area (Gummersbach, Bergisches Land). Blood lead levels were determined in 83 of the children living in the lead-smelter area. On average, tooth lead levels of children living in the smelter area (mean: 6.0 microgram/g; range: 1.49-38.5 microgram/g) were significantly higher than those of children living in the rural area (mean: 3.9 microgram/g; range: 1.6-9.4 microgram/g). Blood lead levels were 6.8-33.8 microgram/100 ml (mean: 14.3 microgram/100 ml). Children of lead-workers had on average higher tooth lead and blood lead levels than children of people who were not lead-workers. Tooth lead levels increased with increasing duration of residence in the lead-smelter area and with the degree of local environmental pollution by lead, as indicated by the lead content of the atmospheric dust fall-out around the children's homes. The correlation coefficient of tooth lead vs blood lead was 0.47. The intra-individual variability of tooth lead levels was low (r = 0.86), and tooth lead levels of brothers and sisters were similar (r = 0.75), suggesting that tooth lead may be used as a representative and reliable indicator of long-term lead exposure.

Child↗

Neuropsychological studies in children with elevated tooth-lead concentrations. I. Pilot study.

In contrast to blood-lead (PbB), tooth-lead concentrations (PbT) provide retrospective information about longterm, cumulative childhood lead-intake. From a basic sample of 458 school age children from the city of Duisburg (FRG), whose lead-concentrations in shed incisor teeth had been measured (means = 4.6 ppm; range: 1.4-12.7 ppm), two extreme-groups of 26 children each (mean age: 8.5 years) with low (means = 2.4 ppm) and elevated (means = 9.2 ppm) PbT were selected. After pair-matching both groups for age, sex, and father's occupational status, these children were tested under double-blind precautions for intellectual performance (German WISC), for perceptual-motor integration (Göttinger Formreproduktionstest = GFT, Diagnostikum für Cerebralschädigung = DCS, Benton-Test), and for gross motor-coordination (Körper-Koordinationstest für Kinder = KTK). Significant (P less than 0.05) inferiority of the lead-children was found in two tests of perceptual-motor integration (increased GFT-errors; lower success rate for DCS). In addition a near significant (P less than 0.1) reduction of 5-7 IQ-points was determined in these children. Although this pilot study has provided some evidence for an association between childhood lead-exposure and neuropsychological impairment, this association cannot yet be considered proven, because the observed effects were discrete and statistically confirmed only in part, and because there was a slight prevalence of perinatal risk factors in the lead group. Further research to clarify the issue is necessary.

Behavior↗

Acute behavioral effects of exposure to some organic solvents -psychophysiological aspects.

Acute low-level exposure to organic solvent vapours may result in prenarcotic states of CNS-depression, often characterized by behavioral dysfunction. Behavioral findings from experimental acute human exposures to toluene, trichloroethylene (TCE), and methylene chloride (MC) are covered in this review. Perceptual measures (e.g. critical flicker fusion = CFF), measures of sustained attention (vigilance), measures of psychomotor performance (as e.g. reaction time, motor speed, coordination) as well as EEG-measures (sensory evoked potentials) are used to illustrate the main effects from such studies. Progressive increase of reaction time was observed at toluene-exposures of only 300 ppm (30 minutes). No consistent behavioral deficit has been reported for trichloroethylene below 300 ppm; instead, visual and auditory evoked potentials were found to be affected at TCE vapour-concentrations between 50 and 100 ppm (3 1/2 - 7 1/2 hours of exposure). CFF-depression, vigilance-decrement and disruption of psychomotor performance has been observed during MC-exposure (200 - 800 ppm; 2-4 hours). Although such behavioral effects are usually considered reversible and of no demonstrated pathological impact, they may nevertheless contribute to accident-prone behavior in occupational settings.

Behavior↗

The neurotoxicity of dichloromethane.

Dichloromethane (DCM) is a clear, waterwhite, non-inflammable liquid of high volatility and sweet aromatic odor. It is widely used as an industrial solvent. In considering its neurotoxicity the CNS-depressant effects of both narcotic and hypoxic action must be taken into account, hypoxia being induced by the established biotransformation of DCM to carbon monoxide (CO). In animal studies depression of motor activity has been observed at high vapor concentrations around 5000 ppm, whereas disturbances of sleep-patterns, namely a depression of REM-sleep, has been shown down to 1000 ppm. Slowing of peripheral nerve conduction velocity occurred after DCM-injections giving rise to COHb between 4 and 6.8%. Controlled human exposure-studies revealed signs of CNS-depression, namely disturbances of psychomotor performance at 800 ppm, depression of the flicker fusion threshold and of vigilance performance down to 300 ppm, as well as performance decrement in a combined tracking-monitoring task at 200 ppm. Comparison of DCM- and CO-exposures matched for COHb revealed more pronounced performance deficit for DCM than for CO, suggesting additivity of narcotic and hypoxic action.

Animals↗

[Neurobehavioral and systemic effects in lead-exposed rats after an exposure-free interval of four months duration (author's transl)].

This experiment was designed to study the degree of recovery from lead-induced neuro-behavioral deficit after normalization of blood lead-level (PbB). Female Wistar-rats were given a diet containing lead-acetate (2260 ppm Pb) for 60 d until mating, giving rise to a PbB-increase from 53 microgram/d1 (before mating) to 84 microgram/d1 (after weaning). Lead-exposure of their male offspring was continued for 4 months with their PbB levelling off at 40 microgram/d1 (table 1). Lead-feeding was discontinued thereafter for another 4 months, PbB declining to a final level of 12 microgram/d1 (table 1). These animals were then compared for neurobehavioral functions to age-matched controls with respect to discrimination-learning (Lashley jumping-stand) and motor activity (open field-test). In addition recovery from initial loss of body-weight after partial food-deprivation was measured, known to be retarded at elevated PbB. The results may be summarized as follows: Formerly Pb-treated animals subsequently raised on a lead-free diet resulting in PbB-normalization within 4 months as compared to untreated controls exhibit (1) significant retardation of recovery from initial loss of body-weight (fig 4), (2) significant increase of error-repetitions in discrimination-learning (table 4; fig. 5) indicating disturbances of learning-performance without a change in learning-speed, and (3) significant hypoactivity (ambulation) without a significant change of other variables of open field-behavior (table 5; fig. 6). These results demonstrate, that some neurobehavioral and systemic symptoms of Pb-related dysfunction persist even after normalization of PbB, thus indicating partial irreversibility of Pb-induced damage.

Animals↗

Neurobehavioral and systemic effects of longterm blood lead-elevation in rats. I. Discrimination learning and open field-behavior.

In order to assess neurobehavioral deficit subsequent to early low-level lead-exposure, Wistar-rats were prenatally Pb-exposed via their mothers, neonatally via their dams' milk, and later on via their diet containing lead acetate (745 mg Pb/kg diet). Blood-lead levels (PbB) of dams increased from 24.2-31.2 microgram-% during pregnancy and suckling-periods, those of offsprings were 26.6 microgram-% at about 16 days of age and 28.5 microgram-% at about 190 days of age. Between 100 and 200 days of age 40 male offsprings were subjected to behavioral testing, namely an open field-test and a visual discrimination-learning task. Two learning-tasks of different complexity, i.e. orientation- and size-discrimination, were used. Data of 20 lead-treated animals were compared with those of 20 age-matched controls. In the open-field test lead-fed animals were significantly more restless than controls; an increase of ambulation, rearing and grooming was observed. In the difficult learning-task, i.e. size discrimination, only the controls did learn the problem, whereas only one of the lead-group did; there was, however, no difference between lead- and control-animals for the easy task, i.e. orientation-discrimination. The observed effects, namely overreaction in the open field and a deficit of visual discrimination learning, may be interpreted in terms of lead-induced CNS-dysfunction. They clearly suggest that the "no-response level" for neurobehavioral damage in the rat, subsequent to early lead-exposure, must be assumed to be lower than 35 microgram/100 ml.

Animals↗

[On the effect of odourants in laboratory and field tests (author's transl)].

Odour nuisance reactions are of considerable importance in environmental hygiene. Their scientific analysis calls for a high degree of flexibility in the selection of adequate "access routes". The present paper deals with results of laboratory and field investigations in conjunction with the problem of odour pollution. In a laboratory test 50 test subjects were exposed for 2 1/2 hours either to H2S stimuli at a level of about 2.5 ppm or to pure air. The following effects were investigated: perception and evaluation of stimuli, subjective feeling as well as ability to concentrate. As expected, perceived intensity and intolerance of the stimulus decreased linearly with the duration of exposure; the subjective feeling and concentration were not significantly affected by smell as was demonstrated by comparative checks. By contrast, field investigations of differently exposed groups of population clearly demonstrated negative effects of odour pollution. 704 inhabitants of the city of Düsseldorf, residing in control and exposed areas, were given standardised questionnaires by interviewers to obtain information on reactions to offensive smell. The multivariate data analysis produced a 3-factor reaction pattern, with factor I (general reaction to offensive smell on a sensory basis) being particularly discriminatory. Moreover, it was found that, under identical exposure conditions, persons with a low adaptive tolerance professed themselves to be much more disturbed by the smell than did others with a higher degree of adaptive tolerance to the nuisance. A comparison of the laboratory findings with the field values suggests that the scientific analysis of reactions to the smell pollution presupposes an existential engagement of the examinee which requires that the disturbing stimulus be "embedded" in the pattern of the daily reality of life. This, of course, can hardly be realized in the laboratory.

Adaptation, Psychological↗

Alteration of the visual evoked potential and the electroretinogram in lead-treated monkeys.

Rhesus monkeys were pre- and postnatally exposed to either 0, 350, or 600 ppm lead acetate in lab chow. At the age of 7-7 1/4 years visual evoked potentials (VEP) and electroretinograms (ERG) were recorded. Flashes were used as stimuli. The VEP was taken under two background illuminance conditions. Lead-related decreases in amplitudes and increases in latencies were observed. Effects on amplitudes were more pronounced under the dark condition while latencies were more affected at the bright background level. The ERG was studied during the course of dark adaptation. The increase in amplitudes of the b-wave during the adaptation period was more prominent in lead-exposed subjects than in controls. Oscillatory potentials were not altered by lead. The findings are discussed in terms of the physiological mechanisms underlying these different potentials.

Aging↗

Significance of hippocampal dysfunction in low level lead exposure of rats.

Previous reports have suggested a relationship between the neurotoxicity of lead and hippocampal dysfunction. Therefore, a comparison between the behavioral changes induced by lead exposure and by selective destruction of hippocampal neurons should help to clarify whether the intrinsic neurons of the hippocampus are directly influenced by lead. Rats maternally and permanently exposed to lead (750 ppm in the diet as lead acetate) were tested in a radial arm maze and compared with controls and rats with ibotenic acid-induced neuronal depletion in the dorsal hippocampus. Lead-exposed groups showed an impairment in the acquisition performance of the spatial task while hippocampally damaged animals did not. When they were retested 4 weeks after the end of the original acquisition, both groups of lead-exposed and ibotenic acid-treated rats showed a significant deficit in retention. These results suggest that this deficit produced by lead can be due to the damage of the hippocampal neurons but not the impairment observed in the acquisition. We propose that the neurotoxicity of lead is not entirely due to the dysfunction of the dorsal hippocampus and that other areas of the brain should be considered. Both maternally and permanently lead-exposed rats showed a similar degree of deficit in acquisition and retention, suggesting a long-lasting effect of early lead exposure.

Animals↗

Modulation of lead-induced performance deficit in children by varying signal rate in a serial choice reaction task.

Evidence is presented showing that serial choice reaction performance is disrupted at low blood lead levels (PbB), and that parametric variation of task characteristics modulates the degree of disruption. This evidence is based on two independent studies in 6- to 9-year-old children living in two lead smelter areas in the cities of Nordenham (N = 114) and Stolberg (N = 109) in West Germany. Average PbB was 8.2 micrograms/100 ml (4.4-23.8 micrograms/100 ml) in the Nordenham sample and 7.4 micrograms/100 ml (4.2-18.0 micrograms/100 ml) in the Stolberg sample. Serial choice reaction performance was assessed by means of the Vienna reaction device in which a random sequence of light and tone signals has to be answered by pressing appropriate response buttons. Correct (hits) and false responses (errors) were evaluated as performance measures, and signal rate was varied in order to achieve easy and difficult task conditions. Exposure-related performance deficit was more pronounced for errors than for hits, more clearcut for high than for low signal rates, and proved significant in both studies after correction for confounding using confounder models of different complexities. Some features of the observed deficit resemble clinical observations in children presenting with attention deficit disorder.

Behavior↗

Neuronal depletion of the amygdala resembles the learning deficits induced by low level lead exposure in rats.

The behavioral deficits observed after lead exposure have been related to limbic system dysfunction. In a previous study it was shown that the neurotoxicity of lead could not be explained by the damage of the hippocampus alone. The purpose of the present investigation was to use behavioral comparisons to test the hypothesis that the intrinsic neurons of several nuclei of the amygdala, where lead has been found to accumulate, can be a target of the effects of the metal as well. A group of rats were maternally and permanently exposed to lead (750 ppm in the diet as lead acetate). Another group of equally aged and housed rats, never experimentally exposed to lead, were injected ibotenic acid into the amygdala. All groups plus sham-operated and unoperated controls were tested in the open field, the radial arm maze, and a passive avoidance task. The results showed that lead exposure (both permanent and maternal) and amygdalectomy produced a) no effect on locomotor activity, b) impairments in the acquisition phase of the radial maze, and c) impairments in passive avoidance. These results suggest an involvement of the amygdala in the neurotoxic action of lead, but not as the only brain structure. The deficits in permanently lead-exposed rats are more pronounced than in only maternally-exposed animals suggesting a longlasting, but not totally irreversible effect of early lead exposure.

Amygdala↗

Results from the European multicenter study on lead neurotoxicity in children: implications for risk assessment.

In order to improve dose-response information on neurobehavioral effects of environmental lead exposure in children, the World Health Organization, Regional Office for Europe (WHO/EURO), in collaboration with the Commission of the European Communities, initiated this international study which was planned, executed and evaluated between 1984 and 1989. Eight groups from eight European countries (Bulgaria, Denmark, Greece, Hungary, Italy, Roumania, W. Germany and Yugoslavia) took part. A common study protocol with inherent quality assurance elements was developed to achieve comparability. Blood-lead concentrations (PbB) were the main markers of exposure. The WISC (4 subtests) for psychometric intelligence, the Bender Gestalt test (GFT version) and the Trail-Making test for visual-motor integration, the Vienna Reaction Device and a delayed RT task for reaction performance, and the Needleman scales for behavior ratings served as behavioral endpoints. All individual studies taken together represent a sample size of 1879 school-age children and cover a PbB range from below 5 to about 60 micrograms/100 ml. Overall statistical evaluation of outcome was done by multiple regression analysis using a uniform confounder model. The strongest and most consistent effects occurred for the Bender Gestalt test (GFT version) and for serial choice reaction performance (Vienna Device). The degree of association with PbB was significant for these variables, although the contribution of PbB to the observed variance never exceeded 0.8%. Psychometric intelligence was also negatively affected, although the consistency of outcome between studies was poor, and the association with PbB only borderline. An effort towards risk assessment was made by calculating the proportion of children at risk, using the observed regression coefficients as well as means and standard deviations.

Child↗

Lead effects on the brain stem auditory evoked potential in monkeys during and after the treatment phase.

Rhesus monkeys were pre- and postnatally exposed to either 0, 350, or 600 mg lead acetate/kg diet continuously until the age of about 9.75 years. At the age of 8-8.25 years (Experiment 1) and 9.25-9.5 years (Experiment 2) brain stem auditory evoked potentials (BAEPs) were recorded. Blood lead levels at the time of testing were about 5, 35, or 55 micrograms/dl for controls, the 350-mg group and the 600-mg group, respectively. There were no clinical signs of intoxications. Clicks varying in sound pressure level (SPL) and rate were used to elicit BAEPs. In addition, the influence of different levels of masking noise was explored in Experiment 1. Four early prominent waves were detected in accordance with other studies of the monkey BAEP. The most reliable wave was No. II. Latencies in the BAEP exhibited the known dependencies on parametric variation for SPL, stimulus rate, and masking level. The 600-mg group exhibited the longest latencies at all stimulus conditions. Analysis of wave II and IV latencies revealed a significant main effect for lead on wave II. At the rate condition there were also signs of latency decreases in the 350-mg group that did not reach significance. Therefore, repetition rate was varied on all SPLs in Experiment 2 to assess the reliability of this effect because similar observations were reported in lead-exposed children. There was no indication of reduced latencies using this extended design. In contrast, significant lead-induced increases in latencies of waves I, II, and IV were revealed by multivariate ANOVA. The purpose of Experiment 3 was to examine whether these results were dependent on current exposure or persisted after cessation of lead treatment. It started 18 months after the end of lead feeding, when blood lead levels had declined to nearly normal values. The same lead-related effects were detected as in the previous experiments. Taken together, these results indicate consistent prolongations of latencies in the BAEP due to subtoxic lead exposure that are not dependent on current treatment. The results are compared to the effects found in epidemiological studies in lead-exposed children.

Aging↗