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Occupational neurotoxicology of organic solvents and solvent mixtures
Neurotoxicologyand Teratology,Vol. 11, pp. 575-578. ©Pergamon Press plc. 1989. Printed in the U.S.A.
0892-0362/89 $3.00 + .00
Occupational Neurotoxicology of Organic Solvents and Solvent Mixtures I GERHARD TRIEBIG
Institute of Occupational and Social Medicine of the University Heidelberg Hospitalstr. 1, D-6900 Heidelberg
TRIEBIG, G. Occupationalneurotoxicologyof organicsolventsand solventmixtures. NEUROTOXICOL TERATOL 11(6) 575-578, 1989.--The results of two field studies in painters and spray painters, the outcomes of examinations of workers with suspected work-related disease due to solvents, as well as data from an evaluation of an epidemiologic study in painters with confirmed occupational disease, are presented and discussed. The results of these studies and the experiences in occupational medicine in the Federal Republic of Germany do not support the assumption of high neurotoxic risks in solvent-exposed workers, which can be postulated from various epidemiologic studies from Scandinavian countries. Several factors may explain the different conclusions: 1) lower solvent exposures of German painters in the past decades; 2) false positive diagnosis of a toxic encephalopathy; 3) aetiologicai misclassification; 4) differences in legislation relevant for the acknowledgement of occupational diseases. In conclusion, there is a need for further well-designed epidemiologic studies in occupationally solvent-exposed workers. Suggestions regarding assessment of exposure and neurobehavioral tests are given. Occupational neurotoxicology
Organic solvents
Solvent mixtures
THE issue of neurotoxicity of organic solvents and solvent mixtures in humans is closely related to the central nervous system (CNS), which can be regarded as a main target organ for adverse effects of this group of chemicals. Besides the CNS, the peripheral and autonomic nervous system may also be involved. Figure 1 demonstrates a general model of the casual relationship between solvent exposure and neurobehavioral effects. During the past decades, numerous experimental, clinical and epidemiological studies were performed predominately in the Scandinavian countries and also later in other industrial countries [for reviews, see (1, 3, 7, 11, 13)]. The proceedings of several international meetings contributed to a better understanding of the manifold discrepancies and difficulties in the evaluation of neurotoxic effects of solvents in the human brain (ICOH 1982, WHO 1983 and 1985, Raleigh Meeting 1985). However, some important questions are still unanswered:
4. What are the reasons for the discrepancy between the high number of patients with toxic encephalopathy in Denmark and the small number of cases in other industrialized European countries?
1. Are the "Painter's syndrome," chronic solvent syndrome, chronic mental impairment, toxic encephalopathy, neurobehavioral effects, CNS effects, dementia, etc., the same health disorders? 2. Which substance or combination of substances in the solvent mixtures is the real cause of the neurobehavioral effects? 3. Can chronic CNS effects occur without acute solvent-related effects of the brain and to what extent are the neurobehavioral effects reversible?
In a multi-disciplinary retrospective study in 1984--1986, 105 house painters were examined. They were employed for at least ten years (median 27 years, range 10-36 years) (15). Fifty-three workers from various professions (nonpainters), who were matched with regard to age, occupational and socio-economic status and preexposure intelligence level, served as control group. Preexposure IQ is equal to verbal IQ, which can be regarded as relatively resistant to (minor) toxic influences (9). The neurobehavioral tests used (questionnaire, self rating
Because it is impossible to deal with all known aspects of this topic, it is the main purpose of this paper to present the current knowledge from our viewpoint of occupational medicine in the Federal Republic of Germany. For this reason, the results of two field studies performed in the Erlangen Institute of Occupational and Social Medicine, and the experiences of examining workers with suspected occupational disease, are given (15,17). In addition, the outcome of an epidemiological evaluation of confirmed occupational disease in German painters is presented (2). FIELD STUDIESIN HOUSEPAINTERSAND SPRAYPAINTERS
1presented at the International Minisymposium "Interdisciplinary Aspects of Neurotoxicology," Dtisseldorf, September 6-9, 1988.
575
576
TRIEBIG
MODEL OF THE CAUSALRELATIONSHIPSBETWEENEXPOSURETO
TABLE 1
SOl.VENTS AND NEUROBEHAVIORALEFFECTS
MEAN VALUES (MV) AND STANDARD DEVIATIONS (SD) AS WELL AS AGE- AND INTELLIGENCE-ADJUSTED MEAN VALUES (MV-A) OF NEUROBEHAVIORAL TEST RESULTS
EFFECTS
EXPOSURE Duration
Painters (N = 84)
Controls (N = 39)
MV
SD
MV-A
MV
SD
MV-A
Difference (significant p<0.05)
Age (years) IQ
40.0 100.4
10.8 12.3
--
44.6 101.2
10.6 12.7
--
0.03 0.75
d2-F% KAI-TR KAI-C K KAI-IQ KAI-GQ WES SVF
11.7 6.3 13.3 102.3 97.6 15.5 6.4
9.6 1.6 3.1 16.3 13.7 8.8 3.8
12.3 6.2 13.0 100.6 97.1 15.6 6.6
11.8 6.4 13.3 102.8 98.4 12.7 7.7
10.0 1.7 2.9 16.9 14.1 7.1 4.5
11.3 6.5 13.6 104.5 98.9 12.6 7.5
0.29 0.13 0.12 0.08 0.25 0.04 0.87
Intensity lOW
L
acute syndrome unlikely, no irreversible syndrome
s h o r t term
high
acute, reversible syndrome irreversible syndrome possible
lOW
~
irreversible syndrome questionable
hlgh
~
irreversible syndrome possible
long term
FIG. 1. General model to illustrate the causal relationships between solvent exposure and neurobehavioral effects.
scales, performance tests, etc.) are closely related to the concept of the "organic brain syndrome" [for details, see (8)]. The battery also includes tests which are similar to those recommended by a WHO expert group in 1985 (19). Table 1 shows the mean values and standard deviations of the test results after controlling for confounders (exclusion criteria) such as former neurological diseases, severe head injuries, excessive alcohol consumption (more than 80 grams per day), hypertension, etc. Because the controls were 4.6 years older on an average, an analysis of covariance was carried out to consider possible effects of age and also of preexposure intelligence level. Therefore, "adjusted mean values ( M V - A ) " should be regarded rather than the " r a w mean values ( M V ) " for comparison of the two groups. The probabilities of error demonstrate only one significant difference: painters had, on average, a higher degree in the subtest "change of personality ( W E S ) . " In all other test variables, the zero-hypothesis (no difference between painters and controls) was maintained. Painters who reported repeated workplace-related prenarcotic symptoms, e.g., when painting in badly ventilated rooms (N = 22), showed a tendency for worse results in the "defect test." Considering the 84 painters, the variable "intensity of exposure" correlated significantly ( p < 0 . 0 5 ) with the values for "change of personality" (r = + . 19) and for "short-term memory capacity" ( r = - . 16). Multiple regression analyses considering years of exposure as well as magnitude of exposure to solvents as parameters of dose however, gave no clear cutoff correlations with the various neurobehavioral parameters (effects) as indicators for a dose-effect relationship. To examine peripheral nervous system functions (PNS), twelve neurophysiological parameters (NCV, latency, amplitudes) were measured. The results for both groups are given in Table 2. There were no significant differences, except in two parameters. These findings, however, do not support the hypothesis of solventinduced dysfunctions of the peripheral nervous, because the mean NCV were faster in painters than in controls. Additionally, there were no consistent correlations which might show higher prevalence rates of abnormal findings with increasing intensity and longer duration of exposure (15). In conclusion, the "Erlangen Painter Study" demonstrated that the solvent exposures common in German house painters did not contribute to an increased morbidity risk of a "chronic encephalopathy," even when painting with solvent-based paints had been practised for decades. Air monitoring with passive and active
sampling devices at 30 current typical workplaces showed that the actual M A K values in the Federal Republic of Germany as well as the "exposure index" is not exceeded (Table 3). However, there are certain indications of a relationship between repeated workrelated complaints after elevated solvent exposures and abnormal test results concerning the variable "change of personality" in 13 out of a total of 18 (72%) painters. It must be emphasized, however, that these findings apply only to the group sample and not for the individual case. RETROSPECTIVE STUDY
In a retrospective study, we analyzed more than 4500 patient records from our Erlangen Institute. In the time period 1964-1984, a total of 74 painters were examined in order to evaluate whether the patient suffered from an occupational disease. Regarding the criteria of our legal insurance system of occupational diseases, a causal relationship between chemicals at the workplace and the disease was probably present in 16 painters (21%). Main diagnosis in 7 cases was a toxic asthma. In this 20-year period, no case of toxic polyneuropathy or encephalopathy as confirmed occupational disease was recognized in house painters (14). However, during the past decade, we have seen several patients from other workplaces with a mild to moderate encephalopathy due to chronic and heavy exposures to various solvents (16). In this context, the halogenated hydrocarbons trichloroethylene, tetrachloroethylene and dichloromethane for degreasing operations have to be mentioned. Aromatic and aliphatic hydrocarbons were relevant only in three cases of spray painters (16). Concerning the results of reexamination of a few patients 2 or 3 years later, there was no improvement in one case of severe acute tetrachloroethylene poisoning. Another patient with a light encephalopathy showed a normal neuropsychiatric status 3 years later (12). These results may be generalized only in a very restricted way and with caution, since the patients came from a limited area located in southern West Germany. However, with regard to the long period of observation of more than 20 years, it is concluded that solvent exposures at current workplaces in the Federal Republic of Germany are in general not associated with high neurotoxic risk. STATISTICS OF OCCUPATIONAL DISEASES IN THE FEDERAL REPUBLIC OF GERMANY
In view of the experiences in occupational medicine with
OCCUPATIONAL NEUROTOXICOLOGY OF SOLVENTS
577
TABLE 2
TABLE 4
RESULTS OF NERVE CONDUCTION VELOCITIES, LATENCIES AND HEIGHT OF AMPLITUDES FINDINGS IN PAINTERS AND CONTROLS
CONFIRMED CASES OF THE SIX MOST FREQUENT OCCUPATIONAL DISEASES IN PAINTERS IN THE TIME PERIOD 1978 TO 1983 IN THE FEDERAL REPUBLIC OF GERMANY
Neurophysiological Parameter
Painters N = 86
Controls N = 39
Differences s = significant n.s. = not significant
N. medianus MCVmax m/sec distal latency
56.7 --- 6.2 3.6 --- 0.5
56.5 --- 5.6 3.7 ± 0.8
n.s. n.s.
48.3 _ 5.3 7.5 4- 4.5
50.9 ___ 10.3 5.7 --- 2.8
n.s. n.s.
msec
dSCV m/sec distal amplitude IxV N. ulnaris MCVmax m/sec dSCV m/sec pSCV m/sec
60.3 ___ 5.9 49.4 4- 5.4 56.9 __- 5.5
61.1 ----_ 9.3 49.1 4- 10.5 54.4 ± 6.4
n.s. n.s. n.s.
N. peroneus MCVmax m/sec distal latency msec
51.0 4- 6.9 5.0 ± 0.9
50.0 --- 6.5 5.0 ± 1.0
n.s. n.s.
N. suralis distal latency msec dSCV m/sec distal amplitude ~V Skin temperature °C Age (years)
Number of Cases
Heavy dermatosis (BK 51 01) Noise deafness (BK 23 01) Bursitis (BK 21 05) Intoxication with benzene, toluene, xylene (BK 13 03) Fluorosis (BK 13 08) Obstructive airways disease (BK 43 02)
72/38.5% 41/22% 11/6% 10/5% 9/5% 8/4%
Total number of confirmed cases: 187. Data given by Butz (2). Total number of employed painters (1978): 160,000.
3.5 ±
0.5
3.5 ___ 0.7
n.s.
43.2 ± 5.9 ±
5.4 2.9
45.0 --- 8.4 5.0 ± 1.6
n.s. n.s.
firmed occupational diseases in the time period 1978-1983 in painters (2) (see Table 4). Regarding about 160,000 employees, heavy dermatosis in accordance with BK 51 01 was the most frequent occupational disease followed by noise-induced deafness (BK 23 01) and bursitis (BK 21 06). Next, a total of 10 cases of chronic intoxication due to the aromatic hydrocarbons toluene and xylene (BK 13 03) are mentioned. Because individual diagnosis is not available, it cannot be determined what organ, liver, kidney, nervous system, etc., was responsible for compensation. However, the total number of cases is very small.
29
n.s.
DISCUSSION AND CONCLUSIONS
n.s.
At present, our results and experiences in occupational medicine do not agree with some findings of other study groups predominantly from the Scandinavian countries. However, there are several reasons which may help to explain the different outcomes.
30
4- 2
39.7 4- 10.8
--- 2
44.6 ± 10.6
Given are mean values with standard deviation.
regard to possible health risks, it is now questioned what prevalence/incidence rates of work-related diseases are observed in German painters. The list of occupational diseases of 1976, revised in 1988, is relevant for this in terms of insurance law. Butz (2) published a documentation on "occupational diseases incidence" based on data on the Employer's Liability of con-
TABLE 3 RESULTS OF AMBIENT AIR MONITORING BY PASSIVE SAMPLING OVER 6 TO 8 HR AT 30 DIFFERENT WORKPLACES
ppm
MAK-Value 1988 (ppm)
EI = (CMax)/(MAK)
Ethylacetate Toluol Butylacetate Methylisobutylketone Xylene Ethylbenzene
50 15 11 11 7 3
400 100 200 100 100 I00
0.13 0.15 0.06 0.09 0.07 0.03
Total
97
CMax
EI = exposure index.
Disease
Sum of E1 = 0.53
1. The solvent exposures of German house and construction painters in the past decades were probably lower than for painters in other countries, especially in Denmark. It is assumed that some Danish painters were exposed to higher solvent concentrations 1950 to 1960 during spray painting indoors without protection equipment. 2. It was claimed that the diagnosis of cerebral damage in workers in Denmark has no scientific basis, but was arbitrary (4). Gade et al. (5), from the Neurological Clinic in Copenhagen, performed a reanalysis of psychological test data in a small group of diagnosed cases, based on comparisons with matched controls. The authors concluded that previous impressions of significant intellectual impairment in the solvent-exposed patients could not be confirmed when the influence of age, education, and intelligence was taken into consideration. At present, it is, however, questionable whether these results are representative and can be generalized. 3. Studies and experiences in various occupational groups like house painters, spray painters, chemical workers, printers, chemical cleaners, floor layers, etc., demonstrate that there are significant differences in the solvent exposures both from a qualitative and a quantitative point of view. Therefore, estimations of neurotoxic risks should include a reliable evaluation of the past and present solvent exposure preferable on the basis of personal air and biological monitoring data.
578
TRIEBIG
4. Because of differences in legal and insurance law criteria for the acknowledgement and compensation of job-related diseases, the figures from other countries are not directly comparable to the conditions in the Federal Republic of Germany. 5. Neurobehavioral tests are important tools in the diagnostic procedure, but they must satisfy a number of requirements like sensitivity, reliability, specificity (6). It must be stressed that for relevant neurobehavioral, psychological and psychiatric evaluation, several confounding factors are of great importance. These are age, preexposure (premorbid, primary) IQ,
intake of alcohol and drugs, former diseases. To avoid aetiological misclassification and to reach substantiated conclusions, these factors have to be controlled. In further studies, the control of age and education as well as preexposure intelligence level should be considered. According to our experience the last parameter is more important than education because it determines the actual efficiency in performance tests far more (9).
REFERENCES 1. Baker, E. L.; Smith, Th. J.; Landrigan, Ph. J. The neurotoxicity of industrial solvents: A review of the literature. Am. J. Ind. Med. 8:207-217; 1985. 2. Butz, M. Die Belastung der Berufe durch Berufskrankheiten. Schriftenreihe des Hauptverbandes der gewerblichen Berufsgenossenschaften, Sankt Augustin, 1986. 3. Cranmer, J. M; Goldberg, L. Proceedings of the workshop on neurobehavioral effects of solvents. Neurotoxicology 7:1-125; 1986. 4. Errebo-Knudsen, E. O.; Olsen, F. Organic solvents and presenile dementia (the painters' syndrome). A critical review of the Danish literature. Sci. Total Environ. 48:45-67; 1986. 5. Gade, A.; Mortensen, E. L.; Bruhn, P. "Chronic painters' syndrome". A reanalysis of psychological test data in a group of diagnosed cases, based on comparisons with matched controls. Acta Neurol. Scand. 77:293-306; 1988. 6. Gamberale, F. Use of behavioral performance tests in the assessment of solvent toxicity. Scand. J. Work Environ. Health 11:65-74; 1985. 7. Grasso, P.; Sharratt, M.; Davies, D. M.; Irvine, D. Neurophysiological and psychological disorders and occupational exposure to organic solvents. Food Chem. Toxicol. 22:819-852; 1984. 8. Lehrl, S.; Kinzel, W.; Fischer, B.; Weidenhammer, W. Psychiatrische und medizinpsychologische Me[3verfahren des deutschsprachigen Raumes. Ebersberg, Vless Verlag; 1986. 9. Lehrl, S. Personal communication; 1988.
10. Spencer, P. S.; Schaumburg, H. H. Organic solvent neurotoxicity. Scand. J. Work. Environ. Health 11:53-60; 1985. 11. Triebig, G. Arbeitsstoff-bedingte Nervenerkrankungen--Aspekte der Begutachtung. Arbeitsmed. Sozialmed. Praventivmed. 19:29-34; 1984. 12. Triebig. G. Gesundheitsgefahrdungen dutch organische Lrsemittel. Arbeitsmedizin aktuell. Lieferung 18. Stuttgart: Gustav Fischer Verlag; 1986. 13. Triebig, G.; Gr(Jner, Ph.; Valentin, H. Berufskrankheiten bei Malern, Anstreichern und Lackierern. Retrospektive empirischkasuistische Analyse von Erkrankungsf~illen der Jahre 1964-1984. Arbeitsmed. Sozialmed. Pr~iventivmed. 21:81-86; 1986. 14. Triebig, G. ErlangerMalerstudie. Multidisziplin~ireQuerschnittsuntersuchung zur Neurotoxizit~it von Lrsemitteln in Farben und Lacken. Arbeitsmed Sozialmed Praventivmed Sonderheft 9. Stuttgart: Gentner Verlag; 1986. 15. Triebig, G.; Grobe, Th. Toxische Enzephalopathie durch chronische Lrsemittel-Exposition als Berufskrankheit. Arbeitsmed. Sozialmed. Praventivmed. 22:222-228; 1987. 16. World Health Organization. Neurobehavioral methods in occupational and environmental health: Extended abstracts from the Second International Symposium. WHO, Document 3, Copenhagen; 1983. 17. World Health Organization. Chronic effects of organic solvents on the central nervous system and diagnostic criteria. WHO, Document 5, Copenhagen; 1985.
0892-0362/89 $3.00 + .00
Occupational Neurotoxicology of Organic Solvents and Solvent Mixtures I GERHARD TRIEBIG
Institute of Occupational and Social Medicine of the University Heidelberg Hospitalstr. 1, D-6900 Heidelberg
TRIEBIG, G. Occupationalneurotoxicologyof organicsolventsand solventmixtures. NEUROTOXICOL TERATOL 11(6) 575-578, 1989.--The results of two field studies in painters and spray painters, the outcomes of examinations of workers with suspected work-related disease due to solvents, as well as data from an evaluation of an epidemiologic study in painters with confirmed occupational disease, are presented and discussed. The results of these studies and the experiences in occupational medicine in the Federal Republic of Germany do not support the assumption of high neurotoxic risks in solvent-exposed workers, which can be postulated from various epidemiologic studies from Scandinavian countries. Several factors may explain the different conclusions: 1) lower solvent exposures of German painters in the past decades; 2) false positive diagnosis of a toxic encephalopathy; 3) aetiologicai misclassification; 4) differences in legislation relevant for the acknowledgement of occupational diseases. In conclusion, there is a need for further well-designed epidemiologic studies in occupationally solvent-exposed workers. Suggestions regarding assessment of exposure and neurobehavioral tests are given. Occupational neurotoxicology
Organic solvents
Solvent mixtures
THE issue of neurotoxicity of organic solvents and solvent mixtures in humans is closely related to the central nervous system (CNS), which can be regarded as a main target organ for adverse effects of this group of chemicals. Besides the CNS, the peripheral and autonomic nervous system may also be involved. Figure 1 demonstrates a general model of the casual relationship between solvent exposure and neurobehavioral effects. During the past decades, numerous experimental, clinical and epidemiological studies were performed predominately in the Scandinavian countries and also later in other industrial countries [for reviews, see (1, 3, 7, 11, 13)]. The proceedings of several international meetings contributed to a better understanding of the manifold discrepancies and difficulties in the evaluation of neurotoxic effects of solvents in the human brain (ICOH 1982, WHO 1983 and 1985, Raleigh Meeting 1985). However, some important questions are still unanswered:
4. What are the reasons for the discrepancy between the high number of patients with toxic encephalopathy in Denmark and the small number of cases in other industrialized European countries?
1. Are the "Painter's syndrome," chronic solvent syndrome, chronic mental impairment, toxic encephalopathy, neurobehavioral effects, CNS effects, dementia, etc., the same health disorders? 2. Which substance or combination of substances in the solvent mixtures is the real cause of the neurobehavioral effects? 3. Can chronic CNS effects occur without acute solvent-related effects of the brain and to what extent are the neurobehavioral effects reversible?
In a multi-disciplinary retrospective study in 1984--1986, 105 house painters were examined. They were employed for at least ten years (median 27 years, range 10-36 years) (15). Fifty-three workers from various professions (nonpainters), who were matched with regard to age, occupational and socio-economic status and preexposure intelligence level, served as control group. Preexposure IQ is equal to verbal IQ, which can be regarded as relatively resistant to (minor) toxic influences (9). The neurobehavioral tests used (questionnaire, self rating
Because it is impossible to deal with all known aspects of this topic, it is the main purpose of this paper to present the current knowledge from our viewpoint of occupational medicine in the Federal Republic of Germany. For this reason, the results of two field studies performed in the Erlangen Institute of Occupational and Social Medicine, and the experiences of examining workers with suspected occupational disease, are given (15,17). In addition, the outcome of an epidemiological evaluation of confirmed occupational disease in German painters is presented (2). FIELD STUDIESIN HOUSEPAINTERSAND SPRAYPAINTERS
1presented at the International Minisymposium "Interdisciplinary Aspects of Neurotoxicology," Dtisseldorf, September 6-9, 1988.
575
576
TRIEBIG
MODEL OF THE CAUSALRELATIONSHIPSBETWEENEXPOSURETO
TABLE 1
SOl.VENTS AND NEUROBEHAVIORALEFFECTS
MEAN VALUES (MV) AND STANDARD DEVIATIONS (SD) AS WELL AS AGE- AND INTELLIGENCE-ADJUSTED MEAN VALUES (MV-A) OF NEUROBEHAVIORAL TEST RESULTS
EFFECTS
EXPOSURE Duration
Painters (N = 84)
Controls (N = 39)
MV
SD
MV-A
MV
SD
MV-A
Difference (significant p<0.05)
Age (years) IQ
40.0 100.4
10.8 12.3
--
44.6 101.2
10.6 12.7
--
0.03 0.75
d2-F% KAI-TR KAI-C K KAI-IQ KAI-GQ WES SVF
11.7 6.3 13.3 102.3 97.6 15.5 6.4
9.6 1.6 3.1 16.3 13.7 8.8 3.8
12.3 6.2 13.0 100.6 97.1 15.6 6.6
11.8 6.4 13.3 102.8 98.4 12.7 7.7
10.0 1.7 2.9 16.9 14.1 7.1 4.5
11.3 6.5 13.6 104.5 98.9 12.6 7.5
0.29 0.13 0.12 0.08 0.25 0.04 0.87
Intensity lOW
L
acute syndrome unlikely, no irreversible syndrome
s h o r t term
high
acute, reversible syndrome irreversible syndrome possible
lOW
~
irreversible syndrome questionable
hlgh
~
irreversible syndrome possible
long term
FIG. 1. General model to illustrate the causal relationships between solvent exposure and neurobehavioral effects.
scales, performance tests, etc.) are closely related to the concept of the "organic brain syndrome" [for details, see (8)]. The battery also includes tests which are similar to those recommended by a WHO expert group in 1985 (19). Table 1 shows the mean values and standard deviations of the test results after controlling for confounders (exclusion criteria) such as former neurological diseases, severe head injuries, excessive alcohol consumption (more than 80 grams per day), hypertension, etc. Because the controls were 4.6 years older on an average, an analysis of covariance was carried out to consider possible effects of age and also of preexposure intelligence level. Therefore, "adjusted mean values ( M V - A ) " should be regarded rather than the " r a w mean values ( M V ) " for comparison of the two groups. The probabilities of error demonstrate only one significant difference: painters had, on average, a higher degree in the subtest "change of personality ( W E S ) . " In all other test variables, the zero-hypothesis (no difference between painters and controls) was maintained. Painters who reported repeated workplace-related prenarcotic symptoms, e.g., when painting in badly ventilated rooms (N = 22), showed a tendency for worse results in the "defect test." Considering the 84 painters, the variable "intensity of exposure" correlated significantly ( p < 0 . 0 5 ) with the values for "change of personality" (r = + . 19) and for "short-term memory capacity" ( r = - . 16). Multiple regression analyses considering years of exposure as well as magnitude of exposure to solvents as parameters of dose however, gave no clear cutoff correlations with the various neurobehavioral parameters (effects) as indicators for a dose-effect relationship. To examine peripheral nervous system functions (PNS), twelve neurophysiological parameters (NCV, latency, amplitudes) were measured. The results for both groups are given in Table 2. There were no significant differences, except in two parameters. These findings, however, do not support the hypothesis of solventinduced dysfunctions of the peripheral nervous, because the mean NCV were faster in painters than in controls. Additionally, there were no consistent correlations which might show higher prevalence rates of abnormal findings with increasing intensity and longer duration of exposure (15). In conclusion, the "Erlangen Painter Study" demonstrated that the solvent exposures common in German house painters did not contribute to an increased morbidity risk of a "chronic encephalopathy," even when painting with solvent-based paints had been practised for decades. Air monitoring with passive and active
sampling devices at 30 current typical workplaces showed that the actual M A K values in the Federal Republic of Germany as well as the "exposure index" is not exceeded (Table 3). However, there are certain indications of a relationship between repeated workrelated complaints after elevated solvent exposures and abnormal test results concerning the variable "change of personality" in 13 out of a total of 18 (72%) painters. It must be emphasized, however, that these findings apply only to the group sample and not for the individual case. RETROSPECTIVE STUDY
In a retrospective study, we analyzed more than 4500 patient records from our Erlangen Institute. In the time period 1964-1984, a total of 74 painters were examined in order to evaluate whether the patient suffered from an occupational disease. Regarding the criteria of our legal insurance system of occupational diseases, a causal relationship between chemicals at the workplace and the disease was probably present in 16 painters (21%). Main diagnosis in 7 cases was a toxic asthma. In this 20-year period, no case of toxic polyneuropathy or encephalopathy as confirmed occupational disease was recognized in house painters (14). However, during the past decade, we have seen several patients from other workplaces with a mild to moderate encephalopathy due to chronic and heavy exposures to various solvents (16). In this context, the halogenated hydrocarbons trichloroethylene, tetrachloroethylene and dichloromethane for degreasing operations have to be mentioned. Aromatic and aliphatic hydrocarbons were relevant only in three cases of spray painters (16). Concerning the results of reexamination of a few patients 2 or 3 years later, there was no improvement in one case of severe acute tetrachloroethylene poisoning. Another patient with a light encephalopathy showed a normal neuropsychiatric status 3 years later (12). These results may be generalized only in a very restricted way and with caution, since the patients came from a limited area located in southern West Germany. However, with regard to the long period of observation of more than 20 years, it is concluded that solvent exposures at current workplaces in the Federal Republic of Germany are in general not associated with high neurotoxic risk. STATISTICS OF OCCUPATIONAL DISEASES IN THE FEDERAL REPUBLIC OF GERMANY
In view of the experiences in occupational medicine with
OCCUPATIONAL NEUROTOXICOLOGY OF SOLVENTS
577
TABLE 2
TABLE 4
RESULTS OF NERVE CONDUCTION VELOCITIES, LATENCIES AND HEIGHT OF AMPLITUDES FINDINGS IN PAINTERS AND CONTROLS
CONFIRMED CASES OF THE SIX MOST FREQUENT OCCUPATIONAL DISEASES IN PAINTERS IN THE TIME PERIOD 1978 TO 1983 IN THE FEDERAL REPUBLIC OF GERMANY
Neurophysiological Parameter
Painters N = 86
Controls N = 39
Differences s = significant n.s. = not significant
N. medianus MCVmax m/sec distal latency
56.7 --- 6.2 3.6 --- 0.5
56.5 --- 5.6 3.7 ± 0.8
n.s. n.s.
48.3 _ 5.3 7.5 4- 4.5
50.9 ___ 10.3 5.7 --- 2.8
n.s. n.s.
msec
dSCV m/sec distal amplitude IxV N. ulnaris MCVmax m/sec dSCV m/sec pSCV m/sec
60.3 ___ 5.9 49.4 4- 5.4 56.9 __- 5.5
61.1 ----_ 9.3 49.1 4- 10.5 54.4 ± 6.4
n.s. n.s. n.s.
N. peroneus MCVmax m/sec distal latency msec
51.0 4- 6.9 5.0 ± 0.9
50.0 --- 6.5 5.0 ± 1.0
n.s. n.s.
N. suralis distal latency msec dSCV m/sec distal amplitude ~V Skin temperature °C Age (years)
Number of Cases
Heavy dermatosis (BK 51 01) Noise deafness (BK 23 01) Bursitis (BK 21 05) Intoxication with benzene, toluene, xylene (BK 13 03) Fluorosis (BK 13 08) Obstructive airways disease (BK 43 02)
72/38.5% 41/22% 11/6% 10/5% 9/5% 8/4%
Total number of confirmed cases: 187. Data given by Butz (2). Total number of employed painters (1978): 160,000.
3.5 ±
0.5
3.5 ___ 0.7
n.s.
43.2 ± 5.9 ±
5.4 2.9
45.0 --- 8.4 5.0 ± 1.6
n.s. n.s.
firmed occupational diseases in the time period 1978-1983 in painters (2) (see Table 4). Regarding about 160,000 employees, heavy dermatosis in accordance with BK 51 01 was the most frequent occupational disease followed by noise-induced deafness (BK 23 01) and bursitis (BK 21 06). Next, a total of 10 cases of chronic intoxication due to the aromatic hydrocarbons toluene and xylene (BK 13 03) are mentioned. Because individual diagnosis is not available, it cannot be determined what organ, liver, kidney, nervous system, etc., was responsible for compensation. However, the total number of cases is very small.
29
n.s.
DISCUSSION AND CONCLUSIONS
n.s.
At present, our results and experiences in occupational medicine do not agree with some findings of other study groups predominantly from the Scandinavian countries. However, there are several reasons which may help to explain the different outcomes.
30
4- 2
39.7 4- 10.8
--- 2
44.6 ± 10.6
Given are mean values with standard deviation.
regard to possible health risks, it is now questioned what prevalence/incidence rates of work-related diseases are observed in German painters. The list of occupational diseases of 1976, revised in 1988, is relevant for this in terms of insurance law. Butz (2) published a documentation on "occupational diseases incidence" based on data on the Employer's Liability of con-
TABLE 3 RESULTS OF AMBIENT AIR MONITORING BY PASSIVE SAMPLING OVER 6 TO 8 HR AT 30 DIFFERENT WORKPLACES
ppm
MAK-Value 1988 (ppm)
EI = (CMax)/(MAK)
Ethylacetate Toluol Butylacetate Methylisobutylketone Xylene Ethylbenzene
50 15 11 11 7 3
400 100 200 100 100 I00
0.13 0.15 0.06 0.09 0.07 0.03
Total
97
CMax
EI = exposure index.
Disease
Sum of E1 = 0.53
1. The solvent exposures of German house and construction painters in the past decades were probably lower than for painters in other countries, especially in Denmark. It is assumed that some Danish painters were exposed to higher solvent concentrations 1950 to 1960 during spray painting indoors without protection equipment. 2. It was claimed that the diagnosis of cerebral damage in workers in Denmark has no scientific basis, but was arbitrary (4). Gade et al. (5), from the Neurological Clinic in Copenhagen, performed a reanalysis of psychological test data in a small group of diagnosed cases, based on comparisons with matched controls. The authors concluded that previous impressions of significant intellectual impairment in the solvent-exposed patients could not be confirmed when the influence of age, education, and intelligence was taken into consideration. At present, it is, however, questionable whether these results are representative and can be generalized. 3. Studies and experiences in various occupational groups like house painters, spray painters, chemical workers, printers, chemical cleaners, floor layers, etc., demonstrate that there are significant differences in the solvent exposures both from a qualitative and a quantitative point of view. Therefore, estimations of neurotoxic risks should include a reliable evaluation of the past and present solvent exposure preferable on the basis of personal air and biological monitoring data.
578
TRIEBIG
4. Because of differences in legal and insurance law criteria for the acknowledgement and compensation of job-related diseases, the figures from other countries are not directly comparable to the conditions in the Federal Republic of Germany. 5. Neurobehavioral tests are important tools in the diagnostic procedure, but they must satisfy a number of requirements like sensitivity, reliability, specificity (6). It must be stressed that for relevant neurobehavioral, psychological and psychiatric evaluation, several confounding factors are of great importance. These are age, preexposure (premorbid, primary) IQ,
intake of alcohol and drugs, former diseases. To avoid aetiological misclassification and to reach substantiated conclusions, these factors have to be controlled. In further studies, the control of age and education as well as preexposure intelligence level should be considered. According to our experience the last parameter is more important than education because it determines the actual efficiency in performance tests far more (9).
REFERENCES 1. Baker, E. L.; Smith, Th. J.; Landrigan, Ph. J. The neurotoxicity of industrial solvents: A review of the literature. Am. J. Ind. Med. 8:207-217; 1985. 2. Butz, M. Die Belastung der Berufe durch Berufskrankheiten. Schriftenreihe des Hauptverbandes der gewerblichen Berufsgenossenschaften, Sankt Augustin, 1986. 3. Cranmer, J. M; Goldberg, L. Proceedings of the workshop on neurobehavioral effects of solvents. Neurotoxicology 7:1-125; 1986. 4. Errebo-Knudsen, E. O.; Olsen, F. Organic solvents and presenile dementia (the painters' syndrome). A critical review of the Danish literature. Sci. Total Environ. 48:45-67; 1986. 5. Gade, A.; Mortensen, E. L.; Bruhn, P. "Chronic painters' syndrome". A reanalysis of psychological test data in a group of diagnosed cases, based on comparisons with matched controls. Acta Neurol. Scand. 77:293-306; 1988. 6. Gamberale, F. Use of behavioral performance tests in the assessment of solvent toxicity. Scand. J. Work Environ. Health 11:65-74; 1985. 7. Grasso, P.; Sharratt, M.; Davies, D. M.; Irvine, D. Neurophysiological and psychological disorders and occupational exposure to organic solvents. Food Chem. Toxicol. 22:819-852; 1984. 8. Lehrl, S.; Kinzel, W.; Fischer, B.; Weidenhammer, W. Psychiatrische und medizinpsychologische Me[3verfahren des deutschsprachigen Raumes. Ebersberg, Vless Verlag; 1986. 9. Lehrl, S. Personal communication; 1988.
10. Spencer, P. S.; Schaumburg, H. H. Organic solvent neurotoxicity. Scand. J. Work. Environ. Health 11:53-60; 1985. 11. Triebig, G. Arbeitsstoff-bedingte Nervenerkrankungen--Aspekte der Begutachtung. Arbeitsmed. Sozialmed. Praventivmed. 19:29-34; 1984. 12. Triebig. G. Gesundheitsgefahrdungen dutch organische Lrsemittel. Arbeitsmedizin aktuell. Lieferung 18. Stuttgart: Gustav Fischer Verlag; 1986. 13. Triebig, G.; Gr(Jner, Ph.; Valentin, H. Berufskrankheiten bei Malern, Anstreichern und Lackierern. Retrospektive empirischkasuistische Analyse von Erkrankungsf~illen der Jahre 1964-1984. Arbeitsmed. Sozialmed. Pr~iventivmed. 21:81-86; 1986. 14. Triebig, G. ErlangerMalerstudie. Multidisziplin~ireQuerschnittsuntersuchung zur Neurotoxizit~it von Lrsemitteln in Farben und Lacken. Arbeitsmed Sozialmed Praventivmed Sonderheft 9. Stuttgart: Gentner Verlag; 1986. 15. Triebig, G.; Grobe, Th. Toxische Enzephalopathie durch chronische Lrsemittel-Exposition als Berufskrankheit. Arbeitsmed. Sozialmed. Praventivmed. 22:222-228; 1987. 16. World Health Organization. Neurobehavioral methods in occupational and environmental health: Extended abstracts from the Second International Symposium. WHO, Document 3, Copenhagen; 1983. 17. World Health Organization. Chronic effects of organic solvents on the central nervous system and diagnostic criteria. WHO, Document 5, Copenhagen; 1985.