Behavioral effects of exposure to organic solvents in carpet layers.

Carpet layers and age-matched controls were investigated both at the beginning of a working day and at the end with four subtests of a neuropsychological test battery (NES2). Exposure to toluene, cyclohexane, ethyl acetate, and heptane was measured with personal air sampling methods. One group of carpet layers used water-based adhesives (WBA) on the day the investigation took place and the other group used contact adhesives (CA) on that day. The WBA group was exposed primarily to toluene, and the CA group was exposed to other solvents as well. Initial (before work) differences in neuropsychological scores between all exposed workers and controls could be attributed to differences in education, the carpet layers being somewhat higher educated. No differences were found between the solvent-exposed and control groups that would suggest persistent effects of chronic solvent exposures. The improvement in test scores over the day was the same in both groups. However, evidence for exposure-related changes in test scores over the day were found within the exposed group.

Symptoms indicative of the effects of organic solvent exposure in Dutch painters.

The report describes the results of a cross-sectional study among two groups of young and older painters and two age-matched control groups. The study was intended to gather information on the occurrence of solvent-exposure symptoms among Dutch workers using a mailed questionnaire. Results indicated that among young painters and to a lesser extent among older painters what is commonly accepted as specific symptoms and additional solvent-related symptoms showed a higher frequency than among the controls. The most interesting observation was a significant relationship between the frequency of periods of heavy exposure and the severity of most symptom categories, whereas there was a lack of consistent relationships with other exposure parameters.

Neurobehavioral effects of long-term exposure to xylene and mixed organic solvents in shipyard spray painters.

A cross-sectional study was performed in shipyard painters exposed to organic solvents and age-matched referents. The work duties of the painters mainly involved spray painting with solvent-based paints containing > 50% xylene. Testing methods consisted of a symptoms questionnaire, measurement of peripheral sensory and motor nerve parameters and computerized performance tests. Results indicate that complaints regarding mood changes, equilibrium and fatigue were more severe in painters than in referents, but were not related to the estimated life-time exposure index. Decreased nerve function was observed in the lower extremities and to some extent in the upper extremities. The refractory period appeared to be a sensitive parameter in motor nerves. Most neurophysiological parameters investigated were significantly related to the exposure index. Behavioral testing revealed impairment of simple visuo-motor performance and complex perceptual coding. A relationship between effects on perceptual coding and the exposure index was also demonstrated.

Behavioral effects of exposure to organic solvents in Dutch painters.

The report describes the results of a cross-sectional study of solvent-exposed young and older Dutch painters and two age-matched control groups. Both traditional and computerized neurobehavioral tests were applied. The study did not detect any major differences between the two groups of painters and their two age-matched control groups. It is argued that this absence of differences is probably not due to a lack of sensitivity of the tests applied or the size of the groups studied. The level of exposure was estimated to be within a range at which previous authors have reported solvent-induced CNS effects.

Comparison of performance from three continents on the WHO-Recommended Neurobehavioral Core Test Battery.

To address the need for standardized test batteries, an expert group convened by the World Health Organization (WHO) and the U.S. National Institute for Occupational Safety and Health during 1983 proposed the Neurobehavioral Core Test Battery (NCTB) to identify nervous system effects of chemical exposures in human populations worldwide. To determine the feasibility of using the NCTB in varied cultures, a cross-cultural assessment was conducted under WHO auspices. Data were collected in 10 countries of Europe, North and Central America, and Asia from over 2300 males and females who were not exposed to chemicals at work, within five age ranges between 16 and 65. Results suggest that performance on two NCTB tests (Simple Reaction Time, Benton Visual Retention) is very similar in a broad range of countries and that performance on four other NCTB tests (Santa Ana, Digit Symbol, Digit Span, Aiming) is relatively more variable from country to country, in both males and females. However, data collected from very poorly educated males in one country revealed very low performance levels suggesting that the NCTB may not provide an adequate reference group for identifying (behavioral) neurotoxic effects in such populations. More research is thus needed on evaluating neurotoxicity in poorly educated subjects.

Health effects of pesticides in the flower-bulb culture in Holland.

In a comprehensive project the health risk for workers using pesticides in the flower-bulb culture was addressed in several studies regarding biological monitoring, occupational hygiene and health effects. With respect to biological monitoring, methods were developed for the analysis of metabolites in urine of captan, pirimicarb, zineb and maneb and the soil fumigant dichloropropene. For dichloropropene in a field study a clear relationship was found between the external personal exposure and the excretion of two metabolites (mercapturic acids) in urine. The application technique distinctly influenced the extent of exposure. For the other substances preliminary measurements were performed in the urine of exposed workers; for captan and pirimicarb the methods are promising for further studies of the uptake of these substances under working conditions. In an occupational hygiene study, the dermal exposure due to different application techniques used in crop protection and bulb disinfection was investigated. This resulted in method specific exposure values (grams/field area of bulbs) that showed large differences between the techniques. These exposure values in combination with information on the type of techniques used, the treated area and the frequency of application were used to calculate a personal exposure index (grams/working life); this is an estimate of the potential (external) exposure of individual workers. In an effect study 137 workers who applied pesticides for more than 10 years (average 20 years) in at least bulb disinfection and crop protection (the most important area's of exposure for the growers) were compared to 73 controls. Tests for autonomic and peripheral nerve functions including the distribution of conduction velocities and refractory periods, were applied as well as computerized neurobehavioral tests and electro-encephalography. Significant effects were found on peripheral nerve function parameters, on measures of attention and perceptual coding and on the amount of beta-activity in the EEG; the data suggest that for the majority of subjects these effects are small. No effects were found on liver and renal function and no difference in the prevalence of symptoms that might be ascribed to the usage of pesticides. In a number of exposed workers a cutaneous allergy to pesticides was found. Based on this study, measures are recommended to diminish effectively the exposure to pesticides in this culture.

The effects of occupational exposure to styrene on high-frequency hearing thresholds.

Subchronic exposure to styrene has been reported to produce high-frequency hearing loss in rats. In humans, hearing thresholds for higher frequencies (greater than 8 kHz) are also more vulnerable to ototoxic drugs than those at lower frequencies. Since hearing loss at frequencies above 8 kHz does not seem to play a role in speech processing, hearing loss at frequencies above 8 kHz in workers exposed to styrene or other solvents might easily escape detection. Therefore, hearing thresholds were evaluated at frequencies up to 16 kHz in workers exposed to styrene and compared to those of a control group of unexposed workers. The airborne concentrations of styrene typically did not exceed 150 mg/m3 although individual exposures did, at times, reach higher values (up to 700 mg/m3). In accordance with the literature, an age-dependent increase in hearing thresholds at high frequencies was found. Compared to controls, workers exposed to styrene did not appear to demonstrate an aggravated age-dependent decrease in hearing high frequencies. A comparison, however, within the experimental group between the least exposed and the most exposed workers revealed a statistically significant difference on hearing thresholds at high frequencies.

Experimental exposure to alcohol as a model for the evaluation of neurobehavioural tests.

The performance characteristics of 4 computerized psychological tests were studied using alcohol as a model compound. Subjects received alcohol (0.5 ml/kg) or placebo in a cross-over design and performance was assessed using the Simple Reaction Time test, the Switching Attention test, the Hand/Eye Coordination test and the Color-Word Vigilance test. Analyses indicated an overall significant effect of alcohol at blood-alcohol levels of 0.03% with response speed on the Color-Word Vigilance test being the most sensitive parameter.

Lead exposure during demolition of a steel structure coated with lead-based paints. II. Reversible changes in the conduction velocity of the motor nerves in transiently exposed workers.

In a group of workers exposed to high levels of lead during five months nerve conduction velocity parameters were evaluated at the termination of exposure, and also three and fifteen months later. At the termination of exposure the mean blood lead level was 4.0 mumol/l, and motor conduction velocities in the median and the ulnar nerves were slower and the distal latencies in the median nerve were longer compared to the values measured 15 months later. Sensory conduction velocities, measured distally in the same nerves, were not depressed compared to the values measured three or fifteen months later. It was tentatively concluded that the effect of lead on the conduction velocity of the motor nerves has an initial reversible phase, dependent on the duration of exposure.

Vibration sensitivity as a parameter for detecting peripheral neuropathy. I. Results in healthy workers.

Two methods of evaluating the threshold for vibration perception were compared. Surprisingly it appears that the theoretically attractive, adaptive forced choice method does not result in lower variability than the method of limits. Moreover two devices were used to evaluate the threshold: the Optacon Tactile Tester and the "multirod". Based on the characteristics of these devices and the known properties of mechanoreceptors, it is argued that the two devices test different mechanoreceptor systems. The high correlation of threshold with age (r = 0.9) found by Arezzo and Schaumburg in measurements with the Optacon could not be reproduced.

Tissue culture and neurotoxicology.

Application of tissue culture in neurotoxicology may serve two purposes. First, they may be used to unravel the mechanism of action of neurotoxic compounds and secondly, they may be used for the screening of neurotoxic agents. Studies belonging to the first group can be subdivided into those aiming at the replication of neurotoxic processes in vivo and into those concerned with non-specific effects of neurotoxicants on cultured cells. The potential usefulness of these types of studies for the development of screening methods is discussed. An investigation of acrylamide neurotoxicity in cultures of cerebral cells serves to illustrate such an approach.

Measurement of the electrotonic length constant in cultured muscle fibres.

The measurement of passive electrical membrane properties in cultured muscle cells is complicated by the fact that the electrotonic length in these cells often exceeds their actual length, leading to serious deviations from the simple infinite cable behaviour. By using very short current pulses for these measurements and integrating the responses, the cells can be made to behave as infinite cables.

Effects of extracts of denervated muscles on the morphology of cultured muscle cells.

Previously, trophic effects of extracts from whole chick embryos and from innervated muscles on cultured muscle cells were described. The present study demonstrated similar effects of extracts from 10-days denervated chick muscles. Extracts from innervated as well as from denervated muscles exsanguinated in vivo with saline prior to dissection showed only marginal trophic activity, suggesting a major contribution of serum components to the trophic effects of tissue extracts. Indeed, serum of adult chicks appeared to have a trophic action similar to that of chick embryo extract.

Sensitivity of several cell systems to acrylamide.

Chick spinal ganglia, chick muscle cells combined with mouse spinal cord explants, C1300 neuroblastoma cells, Chinese hamster ovary cells and newborn rat cerebral cells were exposed to various concentrations of acrylamide in culture. Four morphological and 1 electrophysiological parameters were applied in order to score toxic effects. It appeared that the neurite formation of rat cerebral neurons was the most sensitive criterion showing an effect at 10(-7) M acrylamide.

Effects of innervation by ciliary ganglia on developing muscle in vitro.

Electrophysiological and pharmacological properties of neuromuscular junctions formed in tissue culture between chick ciliary ganglia and chick skeletal muscle cells have been studied. Functional neuromuscular junctions are formed already within 24 h. No functional acetylcholine (ACh) esterase is present at these end-plates. The neurites conduct action potentials to the neuromuscular junctions, where EPPs are generated. Tetrodotoxin (TTX) blocks this nerve conduction but in the presence of TTX MEPP-like potentials remain whose amplitudes are lowered when the Mg2+/Ca2+ ratio in the medium is raised. It is speculated that these large TTX-resistant potentials are multiquantal. The relatively high resting membrane potential in non-innervated muscle fibers was not changed by innervation. ACh-sensitivity was determined by iontophoretical application of ACh to the myotubes. Non-innervated myotubes exhibited an evenly distributed ACh-sensitivity. Local differences in ACh-sensitivity were always gradual and never exceeded a factor of 3. Innervation did not alter the overall ACh-sensitivity, but on functionally innervated muscle cells loci hypersensitive to ACh were found. Hypersensitivity was located within sharply defined areas. Apparently the parasympathetic neurons of the ciliary ganglion are able to form functional neuromuscular junctions with skeletal muscle cells in tissue culture and to induce the formation of regions of high ACh-sensitivity.