Rotogravure Printers Research Articles

Delayed manifestations of CNS effects in formerly exposed printers — A 20-year follow-up

Whether long-term occupational exposure to organic solvents may affect mental and cognitive functioning later in life, remains unclear. In this study, twelve rotogravure printers formerly exposed to toluene and 19 referents, all initially examined in the mid-1980s, were reexamined after twenty years, applying neuropsychological tests, symptoms and social interaction questionnaires, medical examination, and exposure assessment of each individual's cumulative exposure. By far the most extensive exposure, mainly toluene, had occurred before 1985. The printers were found to have deteriorated more than their referents in cognitive functioning affecting reasoning and associative learning. No relevant additional exposure during the lengthy time period between assessments could explain this discrepancy. In addition, printers performed significantly worse than the referents in verbal memory and sustained attention at follow-up, where also a dose–effect relationship was noted for reasoning. While the printers did not report more subjective cognitive complaints than the referents, a slightly higher depression score was noted for the printers. The findings of significantly worse deteriorations in cognitive functioning in previously toluene-exposed printers are in line with our hypothesis that sub-clinical deficits during the working life may become manifest later in life, indicating that exposure may in fact interact with ageing. However, considering the small study groups the results must be interpreted with caution.

Nervous system effects of long-term occupational exposure to toluene.

Forty-three male rotogravure printers with long-term toluene exposure and 31 age- and sex-matched offset printers without toluene exposure were examined in detail. Clinical, neurophysiological, neuropsychological and neuroradiological examinations and assessment of autonomic functions did not reveal any statistically significant differences between the groups. The results suggest that occupational long-term exposure to toluene under these circumstances does not have clinically significant adverse effects on the nervous system. Exposure to toluene seemed to be associated with heavy drinking.

Assessment of Neurobehavioral Performance Among Rotogravure Printing Workers Exposed to Toluene

1 ) O b j e c t i v e s : The aims of this study were to investigate the occupational exposure level to toluene among rotogravure printers and neurobehavioral effects among them. M e t h o d s : Fifty rotogravure printers and 147 controls participated in this study. Environmental and biological monitoring was performed for the investigation of toluene expo - sure level, and neurobehavioral performance test were performed by using the Behavioral Assessment and Research System with Korean language instructions(BARS-K). Results: The major results were as follows; 1. Geometric mean toluene concentrations in the ambient air of 5 rotogravure printing work - places were 10.5 (GSD 5.9)∼181.9 (GSD 17.7), with a grand total of 56.7 (GSD60.9) ppm. 2. The geometric mean urinary hippuric acid level for rotogravure printers of 5 workplaces were 0.31 (GSD 0.11)∼5.14 (GSD 0.55), with the grand total of 1.87 (GSD 2.06) g/g creati - nine. 3. There was a linear correlation between hippuric acid levels in urine and the exposed toluene in air: urine hippuric acid (g/g creatinine)=0.03 toluene (ppm) + 0.15 (r=0.899, p<0.01, n=50). 4. After adjustment for confounders, significant associations were found between toluene exposure and Digit span forwards, Digit span backwards, Tapping preferred hand, Symbol digit and Selective attention trials. Conclusions: 1. Rotogravure printers were occupationally exposed to relatively high concen - tration to toluene, and their neurobehavioral performances were decreased. 2. The BARS neurobehavioral testing program, which minimizes the use of text in the instructions, was very effective in overcoming the cultural barriers in neurobehavioral testing.

Multicenter field trial on possible health effects of toluene: I. Toluene body burdens in workers of the rotogravure industry

Ambient air toluene concentrations as well as corresponding individual blood toluene levels were measured under conditions of a field trial, as basis for a correlation with possible acute effects. While the results of various psycho-physiological and medical evaluations after acute (Neubert et al., 2001) and long-term toluene exposure (Gericke et al., 2001) are published in accompanying papers, this publication deals with the exposure levels and body burdens characteristic of workers in the rotogravure industry in Germany at the time of the investigation (1993–1995). Besides providing some information on the exposure at various work-areas under occupational conditions, the correlation between a time-weighted average of the ambient air concentration with the corresponding blood toluene levels is analyzed. Limitations of such an attempt and possible pitfalls are discussed. In the largest field study so far performed on toluene exposure, 12 companies of the German rotogravure industry (and a total of 1528 volunteers) participated. Altogether, complete data sets, i.e. on both ambient air as well as blood toluene levels, were obtained from 1244 male and 124 female participants of the rotogravure industry with quite different degrees of toluene exposure. Rotogravure printers and their helpers were exposed to the highest toluene concentrations in ambient air. On the day of the evaluation, of 806 male volunteers within this group (of 1261 with verified exposure in air), 35 were exposed to a time-weighted average of 100 ppm (i.e. 375 mg/m 3) or above, and 155 of the printers to concentrations between 50 and 100 ppm. Of the remaining 455 male participants of the rotogravure factories (‘non-printers and helpers’), only three were exposed to toluene concentrations above 50 ppm. Only one of the 124 women working in the rotogravure factories was exposed to an average toluene concentrations above 100 mg/m 3 (i.e. 27 ppm). In 66 of the male volunteers toluene levels in blood of >850 μg/l were measured and 14 showed levels exceeding 1700 μg/l. When attempting to predict the resulting individual blood toluene levels from measurements of ambient air concentrations under field conditions, a considerable uncertainty is to be expected. We found a correlation coefficient of the regression curve of about 0.70, with numerous outliers (and a variation of the 12 factories between 0.52 and 0.88).

Multicenter field trial on possible health effects of toluene: III. Evaluation of effects after long-term exposure

In rotogravure industry, contributing considerably to mass color printing of catalogues and magazines, toluene is still extensively used as paint solvent, and many printers have been exposed to this chemical for several decades. Information on adverse health effects associated with long-term toluene exposure is still controversial. In a multi-center study, adverse health effects possibly associated with long-term toluene exposure were evaluated. In 12 rotogravure factories, 1226 male volunteers were recruited, and sufficient information on exposure and on medical data was compiled for about 1077 of them. Evaluations included: physical examination, standard tests of psycho-physiological and psycho-motoric performances, self-report of subjective symptoms, and data on a variety of laboratory blood tests. The medical data were correlated with the length (months) of toluene exposure, and a rough estimate of the extent of exposure (i.e. highly exposed printers and their helpers versus employees working at locations with low or negligible toluene exposure). A small reference group ( n=109) was selected from companies of the paper industry. When linear regression curves were calculated (test results versus duration of exposure), extremely low overall coefficients of determination ( r 2 adj.) of a few percent were estimated within the data clouds, with sometimes statistically significant P-values. Closer analyses revealed a strong influence of the confounding factor age, no clustering of abnormal values of highly toluene-exposed volunteers, and the vast majority or all values of the highly and long-term toluene-exposed participants staying within the reference ranges. Thus, no medical relevance of P-values <0.05 could be recognized in this evaluation, and there may have been some border-line deviations or results largely occurring by chance in the large trial. In a small cluster of the many rotogravure printers toluene-exposed for more than 20 years, the highest systolic blood pressure values of the study were found, but many possible confounding factors were not taken into account. Data on acute exposure and possible effects are presented in accompanying papers (Neubert et al., 2001a, Neubert et al., 2001b). Restricting the conclusions to the end points evaluated as well as the apparent limitations of the evaluation, no evidence was found that long-term occupational toluene exposure extending over several decades in the rotogravure industry in the Western part of Germany was convincingly associated with chronic adverse health effects or convincingly altered surrogate markers in still working male volunteers. Several peculiarities and pitfalls arising when interpreting medical data associated with such a type of environmental exposure must be considered. Reversibility of alterations previously induced at higher levels of toluene-exposure, as well as a healthy workers effect, cannot be excluded for some of the medical end points evaluated.

Decreases of natural killer cells and T-lymphocyte subpopulations and increases of B lymphocytes following a 5-day occupational exposure to mixed organic solvents.

The authors examined the effects of organic solvents on lymphocyte subpopulations in blood. Natural killer and T-lymphocyte subpopulations and B (CD19+) -lymphocytes were measured with flow cytometry in 16 male rotogravure printers on a Friday and on the following Monday. Numbers of all 3 subpopulations of natural killer cells (i.e., CD57+ CD16+, CD57- CD16+, and CD57+ CD16- cells), 2 subpopulations of T lymphocytes (CD4+ CD45RA+ and total CD8+ cells), and total lymphocytes on Friday were significantly fewer than those found on the following Monday. Conversely, the number of B lymphocytes on Friday was significantly larger than the number on Monday. The number of B lymphocytes was significantly correlated with blood toluene levels on Friday. The alteration in the number of CD57+ CD16+ NK cells from Friday to the following Monday was correlated inversely with the corresponding change in exposure level of toluene on Friday. The authors suggest that the effects of mixed organic solvents (primarily toluene) are recoverable decreases of natural killer cells and T lymphocytes and increases in B lymphocytes.

Somatosensory evoked potentials in workers exposed to toluene and styrene.

Somatosensory evoked potentials (SEPs) were used to evaluate possible subclinical impairment of the nervous system due to occupational exposure to toluene and styrene. A group of 36 rotogravure printers with severe exposure to toluene, 20 workers with severe exposure to styrene in a glass laminate manufacturing plant, and a comparison group of healthy subjects were studied. The severity of exposure was documented by measurements of toluene and styrene concentrations in breathing zone air, by hippuric acid concentration in urine in the group exposed to toluene, and by urinary mandelic acid concentration in the group exposed to styrene. Somatosensory evoked potentials were measured by stimulation of the median nerve at the wrist and the tibial nerve at the ankle. Peripheral conduction velocities (CVs) in both extremities and central conduction time (CCT) after tibial nerve stimulation were significantly decreased in both exposed groups. Significantly prolonged latencies of peripheral and cortical SEPs to median nerve stimulation as well as cortical SEPs to tibial nerve stimulation were found in workers exposed to styrene. Some abnormalities in SEPs at peripheral or spinal and cortical levels were found in eight workers exposed to toluene and six workers exposed to styrene. Of these, in three workers exposed to toluene and two to styrene increased CCT and delayed latencies of cortical responses at normal conduction values in the periphery were found. A trend for increased frequency of abnormal SEPs with duration of exposure to toluene and styrene and alcohol abuse was found. Abnormalities in SEPs in the exposed groups are most probably of multifactorial origin. Central SEP abnormalities in both exposed groups could indicate early signs of subclinical dysfunction at spinal and cortical levels and could be due to toluene or styrene exposure probably potentiated by alcohol consumption in the group exposed to toluene.

Cardiac autonomic dysfunction in rotogravure printers exposed to toluene in relation to peripheral nerve conduction.

The autonomic nervous effects of toluene remain less clear. To clarify this neurotoxicity, ten rotogravure printers and the same number of age-matched unexposed controls were examined, by using the coefficient of variation in electrocardiographic R-R intervals (CVRR), the distribution of nerve conduction velocities (DCV) and the maximal motor and sensory nerve conduction velocities (MCV and SCV) in the median nerve. Also, the C-CVHF and C-CVLF (two component CVs of the CVRR reflecting parasympathetic and sympathetic activities, respectively) were computed from component spectral powers using autoregressive spectral and component analyses. These printers had been exposed to toluene (estimated exposure levels of toluene at 83 ppm) for 1-36 years. The CVRR and C-CVHF were significantly lower in the printers than in the controls. No significant difference between the printers and the controls was found in either any DCV parameters or the SCV in the forearm, except the MCV and the SCV in the palm. In the light of previous work on the brainstem/hippocampus damages due to toluene, these data suggest that toluene causes potential damages in the central autonomic nervous system, mainly parasympathetic hypoactivity.

Urinary excretion of o-cresol and hippuric acid after toluene exposure in rotogravure printing.

In 62 male rotogravure printers, the time-weighted average (TWA) toluene exposure during one workweek ranged from 8 to 496 mg/m3 (median 96). Post-shift urinary excretion of hippuric acid showed a poor correlation with the air toluene concentration. Level of o-cresol excretion ranged from 0.08 to 2.37 mmol/mol creatinine and was associated with the exposure (rS = 0.57, P less than 0.0001), although the variation was considerable. However, this metabolite was significantly influenced by smoking habits, both in the workers (0.34 vs 0.10 mmol/mol creatinine after adjustment to zero exposure for the smokers and non-smokers, respectively; P = 0.03) and in 21 unexposed controls (0.18 vs 0.06 mmol/mol creatinine; P = 0.002). The excretion of these metabolites was followed during vacation, when the workers were unexposed. The shared one-compartment half-time was 44 h (+/- SE 30, 82). After 2-4 weeks of vacation, the concentration of o-cresol was significantly higher for the smokers than the non-smokers (0.14 vs 0.06 mmol/mol creatinine; P = 0.02). No smoking-associated difference was found for the urinary hippuric acid concentration. However, there was an association between alcohol consumption and hippuric acid excretion (P = 0.03); no such difference was shown for o-cresol. These results demonstrate that hippuric acid excretion is unsuitable for biological monitoring of toluene exposure when the exposure level is below 200 mg/m3. Also, in spite of the favourable excretion kinetics, the impact of smoking and the large interindividual variation warrant the same conclusion for o-cresol as a means of monitoring low level exposure in an individual worker.

Hormone status in occupational toluene exposure.

Twenty toluene-exposed rotogravure printers, without signs of solvent-induced toxic encephalopathy, had lower median plasma levels of follicle stimulating hormone (FSH) (3.2 vs. 4.9 IU/L; p = .02) and luteinizing hormone (LH) (6.4 vs. 7.2 IU/L; p = .05) and also lower serum levels of free testosterone (7.8 vs. 86.8 pmol/L; p = .05), respectively, than 44 unexposed referents. The individual time-weighted toluene levels in air were 36 (median; range 8-111) ppm. The printers' median toluene levels in blood were 1.7 (1.0-6.6) mumol/l, and in subcutaneous adipose tissue 5.7 (2.5-21) mg/kg fat. There was a negative association between blood toluene and plasma levels of prolactin. In eight printers, the levels of FSH and LH increased during a 4 week vacation, while the levels of thyroid stimulating hormone, free triiodothyronine, and free thyroxine decreased during the same period. The results indicate a slight, reversible effect of toluene on the cortical level or on the hypothalamic-pituitary axis at exposures well below the permissible levels, possibly mediated through an effect on catecholamine neurotransmission.

Cytogenetic effects in rotogravure printers exposed to toluene (and benzene)

Comparing 21 rotogravure printers exposed to toluene (medians: time-weighted air level 150 mg/m 3, blood toluene 1.6 μmole/1) and 21 unexposed controls (median blood toluene ≤0.01 μmole/1 there was a significant increase in the frequency of micronuclei (MN) in pokeweed mitogen (PWM)-stimulated peripheral blood lymphocytes in the printers, as compared to the controls (2.8‰ vs. 1.5‰; p = 0.03; all p adjusted for age and smoking). The frequency of small MN (size ratio MN/main nucleus ≤0.03) in PWM-stimulated lymphocytes was associated with the exposure (1‰ vs. 0.3‰; p = 0.05). Furthermore, among the exposed subjects there was an association between blood toluene and small MN (0.17‰ per μmole/1; p = 0.0005). Small MN in phytohemagglutinin (PHA) cultures displayed no association with any exposure parameter. However, in the printers, an estimated cumulative exposure index was weakly correlated with the frequency of total MN in PHA-stimulated cells (0.00003‰ per mg/m 3 × year; p = 0.07). Among the printers, chromosomal breaks in PHA-stimulated cells were associated with the duration of earlier benzene exposure (0.03% per year; p = 0.01). The results of this study strongly indicate that toluene causes a clastogenic effect on the B-cells even at low exposure levels. Further, earlier benzene exposure seems to have caused chromosomal breaks in T-cells.

Visual evoked potentials in rotogravure printers exposed to toluene.

Visual evoked potentials (VEPs) from stimulation by checkerboard pattern reversal were examined in 54 rotogravure printers exposed to toluene (all men, aged 22-64 years, duration of exposure 1-41 years). A control group consisted of 46 subjects (23 men and 23 women; aged 22-54 years). Compared with controls the exposed group showed more frequent responses with reduced reproducibility or absence of some waves, or both; the mean P1 wave latency was prolonged and mean amplitudes N1P1 and P1N2 were reduced. The VEPs were abnormal in 24% of workers. The frequency of abnormal VEPs correlated positively with the duration of exposure to toluene and also with the degree of alcohol drinking. No association was found between measurements of VEP and electroencephalogram (EEG) or electromyogram (EMG) examinations. A VEP measurement was made in 78% of the exposed workers two years after the first examination. No statistically significant difference between the two results was found. This suggests a marked stability of the observed VEP changes. These changes can be interpreted as a subclinical sign of dysfunction of the central nervous system (CNS) related to exposure to toluene and also to alcohol consumption.

Chromosome aberrations in rotogravure printing plant workers

Chromosome analysis was carried out in peripheral lymphocytes of 3 groups of workers. In 42 rotogravure printers exposed to rotogravure printing dyes and highly purified toluene at working air concentrations in the range of 104–1170 ppm (390–4380 mg/m 3 for 13 years on average, an increased incidence of aberrant cells and chromatid breaks was observed. In 28 office and technical employees of the same plant, more than half of whom worked 2 h daily in the rotogravure workshop, an increased percentage of aberrant cells and chromatid breaks was also found. The difference between the 2 groups working in the printing plant and 32 controls was highly significant. The high incidence of aberrations could be explained by the exposure to toluene, but the influence of rotogravure printing dyes cannot be excluded. Smoking and high air pollution in the urban area were contributing factors in all 3 groups.

Deaths and tumours among rotogravure printers exposed to toluene.

A cohort of 1020 rotogravure printers exposed to toluene and employed for a minimum period of three months in eight plants during 1925-85 was studied. Air levels of toluene were available since 1943 in one plant and since 1969 in most. Based on these measurements and on present concentrations of toluene in blood and subcutaneous fat, the yearly average air levels in each plant were estimated. They reached a maximum of about 450 ppm in the 1940s and 1950s but were only about 30 ppm by the mid-1980s. Exposure to benzene had occurred up to the beginning of the 1960s. Compared with regional rates, total mortality did not increase during the observation period 1952-86 (129 observed deaths v 125 expected; SMR = 1.03). There was no increase in mortality from non-malignant diseases of the lungs, nervous system, or gastrointestinal and urinary tracts. There was no overall excess of tumours 1958-85 (68 v 54, SMR = 1.26; 95% confidence interval, CI = 0.95-1.7). Among the specific cancers, only those of the respiratory tract were significantly increased (16 v 9; SMR = 1.76, CI = 1.03-2.9). Statistical significance was not attained, however, when only subjects with an exposure period of at least five years and a latency period of at least 10 years were considered. Further, there were no dose response relations with cumulated toluene dose (ppm years). There were no significant increases of tumours at other sites, including leukaemias/lymphomas/myelomas.

Neurasthenic complaints and psychometric function of toluene-exposed rotogravure printers.

In 1985, 30 rotogravure printers exposed to toluene for 4-43 years (median 29) were examined by means of interviews and psychometric testing. They were 33-61 years of age (mean 50). Comparisons were made with a reference group of 72 men aged 27-69 (mean 47). The referents had never been exposed to solvents and were all in good health. The printers were employed by two Swedish companies. The mean exposure levels were 43 and 157 mg/m3 of toluene, respectively, at the two printing shops. Before 1980 the exposure levels had exceeded 300 mg/m3. On Monday mornings, before psychometric testing at the department of occupational medicine, toluene was measured in venous blood samples from most of the exposed subjects. A high proportion of the printers reported fatigue (60%), recent short-term memory problems (60%), concentration difficulties (40%), mood lability (27%), and other neurasthenic symptoms. In the psychometric tests their performance was poorer than the reference group's in most of the tests applied. Even performance on the synonyms test, usually considered resistant to mild brain affliction, was worse in the group of printers. Adjusting for this difference in the group comparisons reduced the group differences substantially. Alcohol consumption above 200 g/week was found to reduce the subjects' psychometric function more than toluene exposure. The printers' sum of neurasthenic complaints correlated negatively with their score in several tests. Exposure variables showed only weak associations with test results. Blood toluene levels were positively correlated with scores in spatial tests. The direction of the correlations suggests that the influence of acute pharmacologic effects is undetectable on Monday mornings before work. In conclusion, we found that exposure to toluene at levels below 157 mg/m3 following long-term exposure did induce neurasthenic problems and might reduce psychometric test performance.

Toluene in venous blood during and after work in rotogravure printing.

Toluene exposure was studied in 62 male rotogravure printers, employed in three plants. The exposure level as measured by personal sampling during a week ranged from 8 to 1080 mg/m3 (median 96). The concentration of toluene in venous blood sampled directly after work correlated significantly with the time-weighted average (TWA) for toluene in air during the preceding workshift (n = 57, Spearman's r = 0.84, P less than 0.00001). The post-shift toluene level in venous blood is usable for biological monitoring of exposure. An air level of 100 mg/m3 corresponds to an average blood toluene level of 2.9 mumol/l; an air level of 300 mg/m3 to 8.2 mumol/l. The elimination of toluene is slow. Thus, toluene was detected in most Monday pre-shift blood samples and the levels increased statistically significantly during the work week (median 0.21 versus 0.42 mumol/l, P less than 0.0001). The toluene level in venous blood sampled directly before work on Thursday/Friday was found to be a function of the estimated mean exposure during the work week. In a multiple linear regression analysis, the mean exposure during the week was a good predictor for the concentration of toluene in venous blood before work at the end of the week (n = 52, r = 0.71). Thus, pre-shift blood values at the end of the week can be used as a biological index for the weekly exposure, when the variation of the ambient toluene concentration is known. The slow decrease of toluene in venous blood was followed in six workers for two weeks after cessation of exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Psychological performance, toluene exposure and alcohol consumption in rotogravure printers.

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.

Occupational exposure to toluene: neurotoxic effects with special emphasis on drinking habits

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.