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Influence of occupational styrene exposure on memory and attention
Neurotoxicologyand Teratology, Vol. 11, pp. 585-586. ©Pergamon Press plc, 1989. Printed in the U.S.A.
0892-0362/89 $3.00 + .00
Influence of Occupational Styrene Exposure on Memory and Attention RUDOLF SCHOENHUBER t AND MASSIMO GENTILINI
Clinica Neurologica, UniversiM degli Studi, 1-41100 Modena, Italy
SCHOENHUBER, R. AND M. GENTILINI. Influence of occupational styrene exposure on memory and attention. NEUROTOXICOL TERATOL 11(6) 585-586, 1989.--Short-term memory, perceptual speed, attention and psychomotor function were studied in 55 workers professionally exposed to styrene. The subjects were grouped according to their urinary styrene metabolites. Those with higher styrene exposure showed a significant impairment of short-term memory only. Occupational styrene exposure
Memory
Attention
Neuropsychological testing
NEUROLOGICAL symptoms, reduced short-term memory and low psychomotor performance have been reported following occupational exposure to styrene. However, the real incidence of neurological impairment is still being debated. Cognitive dysfunction has been shown by simple reaction times (RT), visuomotor coordination (3) and short-term memory investigations. In acute experimental studies and also in some long-term field studies at 25 ppm styrene, threshold for cognitive dysfunction was found. Unfortunately, these abnormalities are similar to those occurring after exposure to other toxic agents and cannot, therefore, be considered specific. Moreover, environmental concentrations do not reflect individual styrene absorption, which is best measured by biological monitoring of the final product of styrene metabolism, mandelic acid (MA). This is eliminated as such in urine, or after being converted to phenylgliossilic acid (PGA). Urinary MA and PGA concentrations, both representing about 85% of styrene metabolised in man, are reliable individual exposure indices. In the present field study, neuropsychological measurements of shortterm memory and various aspects of attention were compared in styrene-exposed workers according to their urinary MA and PGA concentrations.
Subjects were grouped according to their urinary styrene metabolites with a cut-off value of 700 mg/1 MA + PGA, chosen according to cited law. All subjects were first examined after 4 work days, on Friday, and again after 2 rest days, on Monday. Styrene exposure was monitored by gas chromatography of urinary MA and PGA levels. Tests were selected to evaluate short-term memory, perceptual speed, attention and psychomotor function.
Digit Forward Test Strings of digits, from 2 to 8, had to be repeated. For each length the subject had to repeat two strings and the test was discontinued with failure on both strings at a given length. At each length 1 point was given for the first list of each length correctly repeated and an additional 0.5 point if the second list was also repeated correctly (2).
Symbol Digit Test (WAIS) Subjects were presented with a list consisting of alternate rows of abstract symbols and corresponding digits from 1 to 9 and were told to enter the symbols in the blank spaces next to a list of random digits on a form. The subject was asked to fill the blanks with the symbols corresponding to each number. The total score was calculated by the number of blanks filled in 120 seconds.
METHOD The present study refers to all 55 workers (mean age 28 -+ 10 years; 38 males, 17 females), who had to be examined according to the Italian health legislation (Art. 33, DPR 303/56). They were all employed in factories in which at least 5% of workers had urinary levels above 700 mg/1 MA + PGA in previous determinations.
Selective Attention Test Each subject was presented with a matrix of 13 rows of 10 numbers and asked to mark each occurrence of the numbers
IRequests for reprints should be addressed to Prof. R. Schoenhuber, Clinica Neurologica, Largo del Pozzo, 1-41100 Modena, Italy.
585
586
SCHOENHUBER AND GENTILINI
TABLE 1 MEAN TEST RESULTS IN THE 2 GROUPS OF SUBJECTS WITH HIGH (>700 mg/l PGA + MA) AND LOW STYRENE EXPOSURE EXAMINED AFTER 4 DAYS OF EXPOSURE AND AFTER 2 DAYS OFF WORK Low Styrene Exposure Exposure Sel. attention Digits forward Digit-Number Reaction Time
56.49 6.54 57.10 214.60
___ 4.06 ± 1.79 ___ 12.34 ± 34.69
High Styrene Exposure
Rest 55.80 6.38 52.91 233.29
± ± ± ---
Exposure 4.90 1.86 13.25 52.33
56.21 5.71 56.29 202.81
± 5.60 + 2.24 _ 11.56 ± 63.56
Rest 54.64 5.61 52.68 231.89
_+ 6.97 ± 2.04 ± 14.86 ± 41.78
indicated at the top of the matrix. The test was repeated three times. Scores were calculated by the number of correct answers provided in the three matrices in a maximum time of 45 sec per matrix.
exposure group on the digit forward test, t(53) = 2.8157, p < 0 . 0 0 6 , only. However, no differences were found between the subjects in these two groups when the tests were repeated on Monday.
Distributed Attention Test
Alterations of vigilance, visuomotor coordination and slowing of simple RT are reported in subjects exposed to various styrene concentrations and studied with large comprehensive test batteries (1, 3~5). Even if it seems reasonable to assess the behavioral performance by means of test batteries specifically devised for monitoring and controlling professional exposure to toxic agents, it is very difficult to define what is actually measured by each test. Impairment of such test performances is not necessarily related to the mental function the test is supposed to investigate. For these reasons, results should be interpreted with caution. In addition, the abnormalities seen following exposure to toxic agents are similar to those occurring in other CNS disorders. The deficits noted in chronic alcohol or drug abuse are in some ways similar to those seen following exposure to industrial solvents. Therefore, neuropsychological testing should be used as part of an integrated team approach to assess individuals with a history of exposure. In the present study, care was taken to exclude drug and alcohol consumption. Moreover, specific tests were chosen. Nevertheless, no test differences were found two days after the last exposure. Long-lasting effects of styrene seem thus excluded, in agreement with previous field study results (1). Data from our study provide evidence only for a specific short-term memory ability impairment. Although other abnormalities are reported, this pattern is reasonably consistent between studies (6). The differences could relate to intensity and duration of exposure and in measurement techniques.
DISCUSSION
Subjects' ability to distribute attention across both visual fields was studied by asking them to respond to the simultaneous appearance of stimuli on a computer screen. Reaction time of correct responses was measured. The mean test scores were compared in the two groups with high ( > 7 0 0 mg/1 PGA + MA) and low styrene exposure using Student's t-test. RESULTS After 4 days' exposure, irrelevant styrene exposure (less than 100 mg/1) was found in 22, low (between 100 and 700 mg/l) in 19 and high (above 700 mg/1) in 14. After 2 rest days, irrelevant styrene exposure ( < 1 0 0 mg) was found in 47 workers, in the remaining 8, exposure was below 400 mg/1. The mean urinary PGA and M A for the 2 groups were, respectively, 168.05 --- 191.79 and 1851.36±2546.30 mg/1 on Friday and 2 4 . 7 3 ± 4 0 . 1 9 and 91.43 ± 106.74 mg/1 on Monday. A similar age distribution was found in the two groups with high and low exposure (25.79 ± 10.42 vs. 28.32---10.22 years, n.s.). Comparing mean test scores of the 41 subjects with irrelevant and low styrene exposure after 4 consecutive working days and the 14 subjects with high styrene exposure (MA + PGA > 700 mg/1), a markedly poorer performance was found in the high styrene
REFERENCES 1. Cherry, N.; Rodgers, B.; Venables, M.; Waldron, H. A.; Wells, G. C. Acute behaviour effects of styrene exposure: a further analysis. Br. J. Ind. Med. 38:346-350; 1981. 2. De Renzi, E.; Nichelli, P. Verbal and non-verbal short-term memory impairment following hemispheric damage. Cortex 11:341-354; 1975. 3. Gamberale, F.; Lisper, H. O.; Olson, B. A. The effect of styrene vapour on the reaction time of workers in the plastic boat industries. Adverse effects on environmental, chemical and psychotropic drugs. 2:135-148; 1976. 4. Gamberale, F. Use of behavioral performance tests in the assessment of
solvent toxicity. Scand. J. Work Environ. Health 1 l(Suppl. 1):65-74; 1985. 5. Haerkoenen. H.; Lindstrom, K.; Seppaelaeinen, A. M.; Asp, S.; Ernberg, S. Exposure-response relationship between styrene exposure and central nervous system functions. Scand. J. Work Environ. Health 4:53-59; 1978. 6. Mutti, A.; Mazzucchi, A.; Rustichelli, P.; Arfini, G.; Frigeri, G.; Franchini, I, Exposure-effect and exposure-response relationships between occupational exposure to styrene and neuropsychological functioning. Am. J. Ind. Med. 5:275-286; 1984.
0892-0362/89 $3.00 + .00
Influence of Occupational Styrene Exposure on Memory and Attention RUDOLF SCHOENHUBER t AND MASSIMO GENTILINI
Clinica Neurologica, UniversiM degli Studi, 1-41100 Modena, Italy
SCHOENHUBER, R. AND M. GENTILINI. Influence of occupational styrene exposure on memory and attention. NEUROTOXICOL TERATOL 11(6) 585-586, 1989.--Short-term memory, perceptual speed, attention and psychomotor function were studied in 55 workers professionally exposed to styrene. The subjects were grouped according to their urinary styrene metabolites. Those with higher styrene exposure showed a significant impairment of short-term memory only. Occupational styrene exposure
Memory
Attention
Neuropsychological testing
NEUROLOGICAL symptoms, reduced short-term memory and low psychomotor performance have been reported following occupational exposure to styrene. However, the real incidence of neurological impairment is still being debated. Cognitive dysfunction has been shown by simple reaction times (RT), visuomotor coordination (3) and short-term memory investigations. In acute experimental studies and also in some long-term field studies at 25 ppm styrene, threshold for cognitive dysfunction was found. Unfortunately, these abnormalities are similar to those occurring after exposure to other toxic agents and cannot, therefore, be considered specific. Moreover, environmental concentrations do not reflect individual styrene absorption, which is best measured by biological monitoring of the final product of styrene metabolism, mandelic acid (MA). This is eliminated as such in urine, or after being converted to phenylgliossilic acid (PGA). Urinary MA and PGA concentrations, both representing about 85% of styrene metabolised in man, are reliable individual exposure indices. In the present field study, neuropsychological measurements of shortterm memory and various aspects of attention were compared in styrene-exposed workers according to their urinary MA and PGA concentrations.
Subjects were grouped according to their urinary styrene metabolites with a cut-off value of 700 mg/1 MA + PGA, chosen according to cited law. All subjects were first examined after 4 work days, on Friday, and again after 2 rest days, on Monday. Styrene exposure was monitored by gas chromatography of urinary MA and PGA levels. Tests were selected to evaluate short-term memory, perceptual speed, attention and psychomotor function.
Digit Forward Test Strings of digits, from 2 to 8, had to be repeated. For each length the subject had to repeat two strings and the test was discontinued with failure on both strings at a given length. At each length 1 point was given for the first list of each length correctly repeated and an additional 0.5 point if the second list was also repeated correctly (2).
Symbol Digit Test (WAIS) Subjects were presented with a list consisting of alternate rows of abstract symbols and corresponding digits from 1 to 9 and were told to enter the symbols in the blank spaces next to a list of random digits on a form. The subject was asked to fill the blanks with the symbols corresponding to each number. The total score was calculated by the number of blanks filled in 120 seconds.
METHOD The present study refers to all 55 workers (mean age 28 -+ 10 years; 38 males, 17 females), who had to be examined according to the Italian health legislation (Art. 33, DPR 303/56). They were all employed in factories in which at least 5% of workers had urinary levels above 700 mg/1 MA + PGA in previous determinations.
Selective Attention Test Each subject was presented with a matrix of 13 rows of 10 numbers and asked to mark each occurrence of the numbers
IRequests for reprints should be addressed to Prof. R. Schoenhuber, Clinica Neurologica, Largo del Pozzo, 1-41100 Modena, Italy.
585
586
SCHOENHUBER AND GENTILINI
TABLE 1 MEAN TEST RESULTS IN THE 2 GROUPS OF SUBJECTS WITH HIGH (>700 mg/l PGA + MA) AND LOW STYRENE EXPOSURE EXAMINED AFTER 4 DAYS OF EXPOSURE AND AFTER 2 DAYS OFF WORK Low Styrene Exposure Exposure Sel. attention Digits forward Digit-Number Reaction Time
56.49 6.54 57.10 214.60
___ 4.06 ± 1.79 ___ 12.34 ± 34.69
High Styrene Exposure
Rest 55.80 6.38 52.91 233.29
± ± ± ---
Exposure 4.90 1.86 13.25 52.33
56.21 5.71 56.29 202.81
± 5.60 + 2.24 _ 11.56 ± 63.56
Rest 54.64 5.61 52.68 231.89
_+ 6.97 ± 2.04 ± 14.86 ± 41.78
indicated at the top of the matrix. The test was repeated three times. Scores were calculated by the number of correct answers provided in the three matrices in a maximum time of 45 sec per matrix.
exposure group on the digit forward test, t(53) = 2.8157, p < 0 . 0 0 6 , only. However, no differences were found between the subjects in these two groups when the tests were repeated on Monday.
Distributed Attention Test
Alterations of vigilance, visuomotor coordination and slowing of simple RT are reported in subjects exposed to various styrene concentrations and studied with large comprehensive test batteries (1, 3~5). Even if it seems reasonable to assess the behavioral performance by means of test batteries specifically devised for monitoring and controlling professional exposure to toxic agents, it is very difficult to define what is actually measured by each test. Impairment of such test performances is not necessarily related to the mental function the test is supposed to investigate. For these reasons, results should be interpreted with caution. In addition, the abnormalities seen following exposure to toxic agents are similar to those occurring in other CNS disorders. The deficits noted in chronic alcohol or drug abuse are in some ways similar to those seen following exposure to industrial solvents. Therefore, neuropsychological testing should be used as part of an integrated team approach to assess individuals with a history of exposure. In the present study, care was taken to exclude drug and alcohol consumption. Moreover, specific tests were chosen. Nevertheless, no test differences were found two days after the last exposure. Long-lasting effects of styrene seem thus excluded, in agreement with previous field study results (1). Data from our study provide evidence only for a specific short-term memory ability impairment. Although other abnormalities are reported, this pattern is reasonably consistent between studies (6). The differences could relate to intensity and duration of exposure and in measurement techniques.
DISCUSSION
Subjects' ability to distribute attention across both visual fields was studied by asking them to respond to the simultaneous appearance of stimuli on a computer screen. Reaction time of correct responses was measured. The mean test scores were compared in the two groups with high ( > 7 0 0 mg/1 PGA + MA) and low styrene exposure using Student's t-test. RESULTS After 4 days' exposure, irrelevant styrene exposure (less than 100 mg/1) was found in 22, low (between 100 and 700 mg/l) in 19 and high (above 700 mg/1) in 14. After 2 rest days, irrelevant styrene exposure ( < 1 0 0 mg) was found in 47 workers, in the remaining 8, exposure was below 400 mg/1. The mean urinary PGA and M A for the 2 groups were, respectively, 168.05 --- 191.79 and 1851.36±2546.30 mg/1 on Friday and 2 4 . 7 3 ± 4 0 . 1 9 and 91.43 ± 106.74 mg/1 on Monday. A similar age distribution was found in the two groups with high and low exposure (25.79 ± 10.42 vs. 28.32---10.22 years, n.s.). Comparing mean test scores of the 41 subjects with irrelevant and low styrene exposure after 4 consecutive working days and the 14 subjects with high styrene exposure (MA + PGA > 700 mg/1), a markedly poorer performance was found in the high styrene
REFERENCES 1. Cherry, N.; Rodgers, B.; Venables, M.; Waldron, H. A.; Wells, G. C. Acute behaviour effects of styrene exposure: a further analysis. Br. J. Ind. Med. 38:346-350; 1981. 2. De Renzi, E.; Nichelli, P. Verbal and non-verbal short-term memory impairment following hemispheric damage. Cortex 11:341-354; 1975. 3. Gamberale, F.; Lisper, H. O.; Olson, B. A. The effect of styrene vapour on the reaction time of workers in the plastic boat industries. Adverse effects on environmental, chemical and psychotropic drugs. 2:135-148; 1976. 4. Gamberale, F. Use of behavioral performance tests in the assessment of
solvent toxicity. Scand. J. Work Environ. Health 1 l(Suppl. 1):65-74; 1985. 5. Haerkoenen. H.; Lindstrom, K.; Seppaelaeinen, A. M.; Asp, S.; Ernberg, S. Exposure-response relationship between styrene exposure and central nervous system functions. Scand. J. Work Environ. Health 4:53-59; 1978. 6. Mutti, A.; Mazzucchi, A.; Rustichelli, P.; Arfini, G.; Frigeri, G.; Franchini, I, Exposure-effect and exposure-response relationships between occupational exposure to styrene and neuropsychological functioning. Am. J. Ind. Med. 5:275-286; 1984.