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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.

Objectives: Because the brain is the recognized target organ for aluminum toxicity, internal aluminum load and central nervous system functions were investigated among aluminum welders in a shipyard., Methods: Seventeen male welders with a mean age of 37 (range 24-48) years and a history of about four years of metal inert-gas welding on aluminum were the subjects. Aluminum in serum (S-Al) and urine (U-Al) was analyzed with graphite-furnace atomic absorption spectrophotometry. Central nervous system functions were examined with neuropsychological tests, symptom and mood questionnaires, quantitative electroencephalography (QEEG), and P300 evoked responses., Results: The mean S-Al concentration was 0.21 (range 0.03-0.64) mumol.l-1 and the mean U-Al was 2.8 (range 0.9-6.1) mumol.l-1. Although the welders performed normally on the neuropsychological tests, there was a negative association between all four memory tests and U-Al and a positive association between the variability of visual reaction times and S-Al. In the QEEG, the amount of delta and theta activity in the frontal region correlated positively and the amount of alpha activity in the frontal region correlated negatively with S-Al., Conclusions: The S-Al and U-Al measurements indicated increased internal loads of aluminum in most of the welders. This finding is compatible with slowly eliminated aluminum from tissues. The neuropsychological assessment suggested disturbing effects of aluminum on short-term memory, learning, and attention. In the QEEG, a corresponding exposure-effect relationship was found for activity in the frontal region. Further studies are needed on the possibility that exposure to aluminum welding fumes causes harm to human health.

Measurement of gas flow and airway pressure at the Y-piece of an endotracheal tube provides valuable information about airway integrity and basic pulmonary function. We describe the working principle and design of the D-lite sensor (Datex Division, Instrumentarium Corporation, Helsinki, Finland), which, in a single, lightweight adapter piece, encloses flow, airway pressure, and sidestream gas measurement. The main emphasis in the design of this instrument was on reliable and accurate operation during continuous monitoring with exposure to humidity and mucus. Therefore, a robust flow-restrictor element with a pick-off arrangement resembling a Pitot tube was employed. This arrangement has nonlinear characteristics with potential difficulties in the measurement of small flows. However, these inherent drawbacks, together with compensations required because of varying gas fractions and pressure, can be handled by sophisticated computer algorithms at the host-monitor end (Capnomac Ultima [Datex Division, Instrumentarium Corporation, Helsinki, Finland]). Validation methods with main results and a brief review of applications are given.

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.

Ninety-five women undergoing induced abortion were randomly premedicated with oral diazepam, 5 or 10 mg, midazolam 15 mg, or intramuscular placebo, 40-60 min before the induction of anesthesia. Prior to premedication and again prior to the procedure, the women completed the questionnaire sheet for the Profile of Mood States (POMS), and plasma samples for immunoreactive beta-endorphin (ir beta-E) and ACTH were taken. The Oblique Tension-Anxiety (T-A) Factor scores derived from POMS correlated with plasma concentrations of ir beta-E and ACTH after premedication. The T-A scores decreased in women premedicated with diazepam, 5 and 10 mg, or midazolam, 15 mg, but not in women treated with placebo. The women premedicated with midazolam, 15 mg, became more fatigued after premedication. The changes in blood pressure after premedication correlated with T-A scores. A positive correlation was found between heart rate and plasma beta-endorphin concentration. The changes in ir beta-E and ACTH did not correlate with the changes in T-A scores. We conclude that POMS T-A scores are useful for assessment of preoperative anxiety and the effect of premedication. The present study did not provide any reliable proof to confirm the hypothesis of a relationship between plasma concentrations of ir beta-E or ACTH and preoperative anxiety. Since many factors modulate endorphin and ACTH secretion prior to operation, the measurement of endogenous opiates may be of limited value in assessment of the effects of preanesthetic medication.

Twenty one monozygotic twins exposed to organic solvents were compared with their non-exposed cotwins by performance in psychological tests. A further 28 monozygotic twin pairs were examined as a reference group. The study used 11 tests, 10 of which had shown an effect in previous studies on the results of exposure to solvents. Paired comparisons of the test scores showed the exposed twins to have lower performance in associative learning, digit span, and block design. These results agree with two previous studies that used a similar set of tests. Contrary to some other studies, psychomotor speed was not affected, but the results indicated a marginal effect on the control of hand movements. Further comparison of subgroups with a low and a high exposure showed the prevalence of subtle neuropsychological dysfunction to be greater among the more exposed twins.

Genetically obese Zucker rats are hyperphagic, hyperinsulinemic and hyperlipemic. In order to investigate pathophysiological mechanisms underlying hyperphagia in these animals, monoamine metabolism and turnover were studied in discrete hypothalamic nuclei known to participate in the control of feeding behavior. Neurochemical studies in genetically obese Zucker rats and in their lean littermate controls were complemented by investigating feeding behavioral responses to the acute administration of clonidine (15 and 30 micrograms/kg i.p.), an alpha 2-adrenoceptor agonist, and to trifluoromethylphenylpiperazine (TFMPP; 1, 2 and 5 mg/kg s.c.), a putative serotonergic 5-hydroxytryptamine-1B receptor agonist. Obese Zucker rats had significantly lower concentrations of 5-hydroxyindoleacetic acid, the main deaminated metabolite of 5-hydroxytryptamine, in the nucleus paraventricularis (PVN) and in the nucleus ventromedialis (VMN), when compared to their lean littermate controls. The rate of accumulation of 5-hydroxytryptophan after decarboxylase inhibition was reduced in the PVN, nucleus supraopticus, nucleus periventricularis and nucleus suprachiasmaticus of the obese rats. No differences were observed in basal concentrations of norepinephrine, dopamine or 3,4-dihydroxyphenylacetic acid between obese and lean Zucker rats in the brain areas studied. However, the rate of accumulation of 3,4-dihydroxyphenylalanine was lower in the VMN and in the median eminence of the obese rats. The feeding behavioral tests showed significantly augmented hyperphagic responses to clonidine in obese Zucker rats. The anorexic effect of TFMPP was similar in both phenotypes. It is concluded that serotonergic activity is reduced in obese Zucker rats, particularly in the PVN, which plays a key role in the control of feeding behavior. The reduced serotonergic activity may be associated with enhanced alpha 2-adrenoceptor-mediated feeding responses in obese Zucker rats.(ABSTRACT TRUNCATED AT 250 WORDS)

The efficiency of timing models of cessation of growth of northern woody plants was defined as their ability to allow maximum utilization of the growing season without autumn frost damage. The efficiencies of three timing models were compared with the aid of computer simulations, using long-term meteorological data. A model based on night length was the most efficient, followed by one based on a joint factor of the night length and temperature sum. A model based on temperature sum alone was the least efficient. The reason for these differences in efficiency was the great year-to-year variation in the annual temperature sum accumulation. The results were compared with empirical evidence for each of the models. The relevance of the theoretical approach is discussed, as well as the application of the simulations.

A prospective follow-up study on new lead workers who began work at a storage battery factory was carried out between 1975 and 1981. Psychological performances (eg, intelligence, memory, visuomotor functions, vigilance, and personality) were assessed before the commencement of exposure and after one, two, and four years of work. Of an initial number of 89 workers, 24 were available for the one-year, 16 for the two-year, and 11 for the four-year reexamination. The time-weighted average blood lead values ranged between 0.68 and 2.17 mumol/l (14 and 45 micrograms/100 ml, respectively). A reference group, nonexposed workers in a cable manufacturing plant and an electrical power plant, was similarly followed. Initially the average psychological performances were similar among the lead workers and the referents. For some of the psychological tests learning effect, which was clearly evident among the referents during the follow-up, was almost absent among the lead workers. The lead worker's visual intelligence and visuomotor functions in particular were impaired significantly after the first two years of follow-up. When the lead workers were divided into two groups according to the median time-weighted average of the blood lead values (1.30 mumol/l), the Block Design and the Santa Ana coordination tests were those which best separated the subgroups. Although the impairment of the lead workers' performance was rather slight and the dispersion in the psychological changes was wide, it was evident that some higher nervous functions were affected by lead levels above about 1.45 mumol/l.

Using a prospective, follow-up approach a group of storage battery plant workers was tested by means of a number of psychodiagnostic tests, as e.g., subtests of the WAIS and WMS, Bourdon-Wiersma test, Santa Ana test, before and two years after entering lead-works. Their performance was compared with that of an age-equivalent group of non-exposed controls. Blood lead levels of the lead group increased from an initial 15.3 +/- 6.7 micrograms/dl (Mean +/- SD) to a final 30.5 +/- 9.6 micrograms/dl after two years, whereas the corresponding PbB-value of the controls was 10.5 +/- 3.7 micrograms/dl and 10.3 +/- 4.0 micrograms/dl, respectively. In the primary psychological examination there were no detectable performance differences between the exposed and controls. Whereas the control group displayed pronounced performance improvement due to training for most of the tests over the two-year period, a sizeable portion of the exposed group exhibited even performance deterioration. Group-comparisons were tested by the non-parametric ch 2-test and two-sided Kolmogorov-Smirnov test. The most sensitive indicators of psychological impairment among the lead workers were Block Design test, Santa Ana coordination test and Digit Span test. It is concluded that the impairment of CNS function, as evidenced by differential test performance, was caused by lead exposure. No exact threshold for impaired performances could be estimated.

Neurotoxic effects of toluene were examined in 43 male rotogravure printers exposed to toluene (age 27-63, mean 41 years; duration of exposure 11-40, mean 22 years) and 31 male offset printers of the same age with slight exposure to aliphatic hydrocarbons. A neurological examination, tests for autonomic nervous function, electroencephalography, psychological tests and computerized tomography of the brain were carried out in addition to a standardized interview. Exposure levels were evaluated for each person separately on the basis of his work history and the results of an earlier study on exposure levels at the same printing shops. Besides a thorough history of alcohol consumption, information about the printers' drinking habits was obtained from the occupational health care centers of the printing shops. The examinations found only slight abnormalities, and there were no statistically significant group differences in the prevalences of abnormalities. No correlations between the abnormalities and the exposure indices were found either. One of the retired workers, however, who had been exposed to high toluene concentrations for over 40 years, had been diagnosed as having chronic organic solvent intoxication. Heavy drinkers of alcohol were clearly more common in the toluene-exposed group. This study detected no clinically significant abnormalities attributable to toluene alone among workers exposed to 68-185 ppm (mean 117) of toluene for over 10 years. The connection between alcohol consumption and toluene exposure is interesting and deserves further study.

A psychological test battery was administered to a group of 43 rotogravure printers exposed to toluene (mean age 41 years, mean duration of exposure 22 years) and to a referent group comprising 31 offset printers of the same age. Eighteen of the rotogravure printers and one of the referents were heavy drinkers of alcohol. The test battery included tests for verbal and visual cognition and memory, perceptual motor speed, and psychomotor abilities. A vocabulary test (Synonyms) was used as a measure of initial intelligence. Performances in the two groups were compared, and descriptive data analyses were made in four subgroups formed according to toluene exposure and drinking habits. The rotogravure printers performance was inferior to the referents in tests measuring visual cognitive abilities. The mean test performances in the subgroups indicated that the difference in drinking habits did not explain the differences: the heavy drinkers tended to perform better than those with more moderate drinking habits. An antagonistic interaction between toluene and alcohol was suggested by intact performances among the heavy drinkers with high exposure (n = 8). The question deserves to be investigated further.

Five studies dealing with long term occupational exposure to carbon disulfide, a mixture of organic solvents, toluene, styrene and lead are reviewed. All of the studies were cross-sectional, comprising either a comparison between exposed and nonexposed groups or the determination of exposure-response relationships, or both. The tests for the cognitive functions were known clinical intelligence and memory tests. The perceptual and psychomotor tasks were the Santa Ana test, the Bourdon-Wiersma test for visual-motor speed and accuracy, the Symmetry Drawing test and the Mira test. In four of the five studies the neurotoxic effect involved both cognitive and psychomotor functions. In the carbon disulfide group, psychomotor retardation was the most pronounced effect: in the group exposed to solvent mixtures the main effects were seen in the cognitive functions. The effects of styrene were limited to perceptual and psychomotor disturbances. As the most sensitive methods have varied from study to study, the continued use of broad and diverse psychological methodology in studies dealing with long term neurotoxic effects is proposed.

Research of the last decades has yielded information about behavioral changes in workers exposed to neurotoxic chemicals and in patients with occupational intoxications. However, the existing documentation does not provide a detailed neuropsychological description of the toxic syndrome. A comparison of the performances of patients with intoxications due to lead, carbon disulphide and organic solvents indicated some differences in the three neurobehavioral syndromes. In the lead intoxication the effect was rather general, whereas psychomotor retardation was the most prominent feature in the carbon disulphide intoxication, and cognitive disturbance in the solvent intoxication. On the other hand, a follow-up of organic solvent patients indicated that the syndrome caused by organic solvents is not static, but changes do occur after cessation of the exposure: most often improvement of cognitive functions, with the exception of the memory, and further retardation of psychomotor speed. The behavioral changes and their prognosis show, however, considerable individual variation, due to the variation of the premorbid ability structure and personality, and to variation of the exposure history.

The behavioral effects of long-term exposure to a mixture of organic solvents were investigated in a comparison of the test results of 100 car painters with those of a reference group. The test battery included tests for intelligence, memory, psychomotor performances, and personality. In addition to the comparison of the mean results, two discriminant function analyses were made. In one, only the performance test variables were used, but in the other personality variables were also included. The results indicated impairments in psychological performances, as well as personality changes in the exposed group. Impairments in visual intelligence and verbal memory and a reduction of emotional reactivity were the central features of the adverse effects of solvent exposure, but the behavioral disturbances also involved several other functions, including performance on a verbal intelligence test. The possible role of the differences in the initial intelligence levels were controlled with a separate comparison of the test results of 33 pairs of exposed and nonexposed subjects who were matched for age and for their intelligence level, measured during the military service. The discriminant function analyses were based on the results of these matched subgroups and tested in the rest of the material. According to the results the sensitivity of the psychological test methods was high, but the specificity somewhat low, with regard to solvent exposure. The concentration of various solvents included in the exposure of car painters were low, the summated exposure corresponding corresponding to 32% of the Finnish threshold limit value. The possible role of a potentiating effect of the solvent in the development of behavioral disturbances is discussed.

In a cross-sectional study the psychological test performances of a group of 36 male chlorine-alkali workers were compared with the level of exposure to mercury and to the corresponding results of referents. The mercury exposure had lasted for at least 10 years and had been controlled by regular health examinations and urine analyses. Several dose indicators were calculated. The more heavily exposed workers performed more poorly on the verbal intelligence test (Similarities) than the referents did. Impairments in the memory tests showed a statistically significant correlation with the actual exposure level, especially with the actual concentration of mercury in blood. The monitoring of mercury in blood can be useful in health surveillance programs. The level of mercury in the air was calculated from the dose indicators. The results support the recommended exposure limit of 25 micrograms/m3 for metallic mercury vapor in the air as a level avoiding adverse effects in exposed workers.

Decisive for my long-term involvement in behavioral toxicology were the hours spent in interviewing and testing patients with occupational poisonings during the first years of my career as a clinical psychologist within the framework of occupational medicine. Important auxiliary factors were the innovative and inspiring scientific climate at our Institute, and the supportive kind of scientific education provided by this environment during the years. It has been rewarding and exciting to follow the international progress of behavioral toxicology. Advances in this special domain of research were and are partly related to advances in occupational epidemiology and toxicology, in neurotoxicology and other allied disciplines, as well as to advances in other branches of psychology. But the major challenge to behavioral toxicology during the first decades of its existence has been finding its place and role within these disciplines. Important challenges for the next decades are defining further the exposure-effect relationships as a basis for the standard setting, extending the surveillance of neurotoxic hazards to the developing countries, and searching for better understanding of the practical significance o neurobehavioral effects, eg, from the point of view of the afflicted individual. To realize these aims, further efforts are needed to coordinate the field of behavioral toxicology and to augment communication between those immediately involved.

Concentrations of halothane and nitrous oxide were assayed by gas chromatography throughout a working day in three operating theatres and in the end-tidal air of 19 nurses 15 and 60 min after leaving the theatres. Perceptual, psychomotor and driving skills were measured in these nurses and in 11 younger nurses working in the wards of the same hospital. A complicated psychomotor test battery and a driving simulator were used. End-tidal air concentrations of halothane and nitrous oxide were positively correlated with the exposure level of these gases in the operating theatres. Some of the operating room nurses had greater amounts of halothane in their end-tidal air (average 15 to 10 ppm) than student volunteers 4.5 h after 3.5 min of general anaesthesia with a combination of halothanenitrous-oxide oxygen (10 ppm halothane). These volunteers had worse psychomotor and driving performances when measured than controls who had not been anaesthetized. No correlations were found between the concentrations of halothane or nitrous oxide in end-tidal air and psychomotor or driving performance. Despite their higher age and exposure to the operating room environment, the driving skills of the operating room nurses were similar to those of the ward nurses. The results suggest that tolerance to anaesthetic gases develops among operating room personnel. No impairment of driving skills can be expected after daily exposure to halothan and nitrous oxide among long-term employees in operating theatres.

Subjective symptoms and psychological performances on a computer-administered test battery were studied among a group of 60 chlorine-alkali workers and their matched referents. The exposure time of the group exposed to inorganic mercury vapor had been about 14 years, and the estimated long-term average exposure had been about 25 micrograms/m3 of air. The exposed workers had an actual mercury concentration of 51.9 (SD 25.0, range 15-150) nmol/l in blood and 84.1 (SD 56.6, range 15-260) nmol/l in urine. Neither perceptual motor nor memory nor learning abilities of the mercury-exposed workers showed any disturbances in a comparison with the referents. However, the exposed group reported statistically significantly more memory disturbances than the referents. Strain caused by three-shift work was a possible cofactor for other increased subjective symptoms, namely, for sleep disorders, fatigue, and confusion.