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Neurobehavioral Effects of Occupational Exposure to Organic Solvents Among Male Printing Workers in Hong Kong a
b
b
Hong Song , Ignatius Tak-Sun Yu & Xiang Qian Lao a
Department of Preventive Medicine, School of Public Health, Sun Yat-Sen University, Guangzhou, China b
Division of Occupational and Environmental Health, School of Public Health and Primary Care, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China Accepted author version posted online: 01 Aug 2013.
Click for updates To cite this article: Hong Song, Ignatius Tak-Sun Yu & Xiang Qian Lao (2015) Neurobehavioral Effects of Occupational Exposure to Organic Solvents Among Male Printing Workers in Hong Kong, Archives of Environmental & Occupational Health, 70:3, 147-153, DOI: 10.1080/19338244.2013.828676 To link to this article: http://dx.doi.org/10.1080/19338244.2013.828676
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Archives of Environmental & Occupational Health (2015) 70, 147–153 C Taylor & Francis Group, LLC Copyright ISSN: 1933-8244 print / 2154-4700 online DOI: 10.1080/19338244.2013.828676
Neurobehavioral Effects of Occupational Exposure to Organic Solvents Among Male Printing Workers in Hong Kong HONG SONG1, IGNATIUS TAK-SUN YU2, and XIANG QIAN LAO2 1
Department of Preventive Medicine, School of Public Health, Sun Yat-Sen University, Guangzhou, China Division of Occupational and Environmental Health, School of Public Health and Primary Care, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China 2
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Received 6 March 2013, Accepted 25 June 2013
The objective of this study was to investigate the neurobehavioral effects of long-term occupational exposure to low levels of organic solvent among male printing workers in Hong Kong. A total of 115 printing workers exposed to organic solvents were recruited from the printing divisions of 3 printing factories, and 101 workers from the binding divisions of the same factories constituted the comparison group. Active and passive samplings were used to assess the occupational exposures to solvents. The World Health Organization Neurobehavioral Core Test Battery (WHO-NCTB) was applied to assess the neurobehavioral functions. Both active and passive sampling results showed that solvent levels were higher in the printing divisions than the binding divisions. The scores of Digit Symbol and Pursuit Aiming were poorer among workers in the printing divisions (all p values < .05). There were no significant differences found between the 2 divisions for other WHO-NCTB tests. The scores of Digit Symbol and Pursuit Aiming showed exposure-response relationship with various solvent exposure indices. Prolonged occupational exposure to low levels of organic solvents was associated with adverse neurobehavioral effects among male printing workers in Hong Kong. Keywords: neurobehavioral, organic solvents, printing
Organic solvents are widely used in painting, dry cleaning, printing, and adhesive manufacturing industries. It is well established that occupational exposure to high levels of organic solvent in air may impair the functions of the central nervous system.1–3 Threshold limit values have been set up in most developed countries, and high level exposures to solvents are expected to become less common. However, the neurotoxic effects of long-term, low-level exposure to organic solvents remain unclear.2 Some studies in the past several decades have shown that low-level exposures to organic solvents were associated with poor cognitive and motor performance,4–10 but the results were not always consistent.11–14 Several reviews have criticized the methodological flaws of the individual studies, including small sample size, selection bias, poor choice of matching controls, and the lack of standardized neuropsychological assessment methods.2,15–18 Therefore, although the
Address correspondence to Professor Ignatius Tak-Sun Yu, School of Public Health and Primary Care, 4th Floor, School of Public Health, Prince of Wales Hospital, Shatin, New Territories, Hong Kong. E-mail: [email protected]
volume of literature is great, the association between neurological dysfunction and prolonged low-level occupational exposure to solvents has remained a focus of research. The association between neurological dysfunction and prolonged low-level occupational exposure to solvents has remained a focus of research.17 Offset lithography printing and letterpress printing are the most widely used printing methods today. The ink, fountain solution, and cleaning materials used in the printing industry contain volatile organic compounds (VOCs), and printing workers are typically exposed to low levels of organic solvents in air during the operations. In the United States, the printing industry consisted of more than 36,000 establishments, with around 1 million employees and generated over $166 billion in sales in 2008.19 In Hong Kong, statistics for the year 2007 showed that 38,563 employees were working in 4,105 printing, publishing, and allied establishments.20 We have shown that exposure to mixtures of organic solvents increased the risk of neurological symptoms among printing workers in Hong Kong.21 However, data concerning neurobehavioral effects of low-level exposure to solvents are limited. We therefore investigated the chronic neurobehavioral effects of low-level occupational exposure to organic solvents among printing workers in Hong Kong.
148 Methods
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Setting and Participants An on-site investigation on the manufacture flow in local printing factories was conducted prior to the present study. Workers in printing divisions were generally exposed to mixed solvents on a daily basis, since they were involved in operating machines, assembling films, making plates, and cleaning equipment that used organic solvents. On the other hand, workers in binding divisions were generally not exposed to solvents, since their work only involved binding paper and packing products. We identified 3 printing factories of different employment sizes in Hong Kong and recruited workers from the printing divisions as the exposed group and workers in the binding divisions as the comparison group. In order to ensure consistent exposure levels over the past years for the workers, we selected the factories in which there were no substantial changes (including equipments and spaces) in the work environments over the past decade. The study was approved by Ethics Committee of the Chinese University of Hong Kong. Each participant signed a written consent prior to participation in the study. Previous studies have shown that the differences in the scores of Santa Ana Dexterity and Digit Symbol by solvent exposure status ranged from 4 to 9.7,22 We therefore estimated that a total of 200 workers would be sufficient to detect differences in the neurobehavioral test scores between the exposed and control groups in our study. Since the proportion of female workers was very low in the local printing industry,21 we only included male workers in the present study. Among the total 320 male workers in the 2 divisions of the 3 selected factories, 12 were excluded due to 1 or more of the following: aged over 55 years, taking sedative medication, and history of a disease that could affect neurobehavioral performance (eg, head injury with loss of consciousness). Of the remaining 308 workers eligible, 216 agreed to participate in the study and completed the interview and neurobehavioral tests (response rate: 70.1%), with 115 workers from the printing divisions and the other 101 from the binding divisions.
Song et al. The interviews and tests were conducted at the beginning of work shifts to ensure at least 12 hours without from solvent exposure at work, so that acute effects of solvent exposure on test performances could be minimized. Questionnaire The WHO -NCTB pretest interview questionnaire was adapted and applied in the present study, with questions covering general personal information, work histories, health statuses and living habits, history of diseases, current symptoms, nonoccupational exposures, and pretest conditions. Neurobehavioral Tests The WHO-NCTB was applied in the present study to assess neurobehavioral functions.23,24 The WHO-NCTB consists of the Profile of Mood States test (POMS), Digit Span test (DSP), Santa Ana Dexterity test (SA), Digit Symbol test (DSY), Benton Visual Retention test (BVR), Pursuit Aiming (PA), and Simple Reaction Time test (SRT). The tests were performed and interpreted strictly in accordance with the operational guide.23,24 All examiners received training before the formal investigation. The POMS test form was adapted using the local dialect, Cantonese. The form was translated into Cantonese based on the simple Chinese version, which had been used in China widely and proven to be of good validity.25 Before we used the Cantonese version in the field, the form were checked by 2 native Cantonese speakers and tested in another 2 Cantonese speakers to make sure that the description in Cantonese is appropriate and understandable. The neurobehavioral test scores were modified to standard scores in order to make the results easy to compare with other studies. In addition, standard scores could change the results to the same direction by reversing the Z score when larger scores indicated a negative effect. The standard scores were calculated by the following formula: Standard score = [(raw score minus mean) /standard deviation] × 10 + 50 The mean and standard deviation were computed from scores of all subjects.
Data Collection Each worker first signed a letter of consent to participate, and then completed a questionnaire through an interview by a trained investigator. The contents of the questionnaire were mainly based on the World Health Organization Neurobehavioral Core Test Battery (WHO-NCTB) annex pretest interview questionnaire. Neurobehavioral tests were then performed using the WHO-NCTB.23,24 The interview and tests were conducted in interview/test rooms set up especially for the study in each factory. The rooms were air conditioned, free from distracting noise, with adequate lighting and several sets of comfortable tables and chairs. Each NCTB test station was manned by a trained researcher, and each worker went through all the test stations in turn. All tests in each factory were completed within 2 to 3 days, during which production was pretty stable.
Exposure Assessment Solvent exposure was assessed using both active and passive sampling. For active sampling, the sampling locations were closed to the workstations where the workers operated. The height of the samplers was around 1.5 m, which is the height of the breathing zone of a typical worker. The sampling was performed for a work shift during the normal operation once, and time-weighted average was calculated. The sampling system consisted of the charcoal tube (800B; Kitagawa; Komyo Rikagaku Kogyo K.K., Kawasaki-City, Japan) and sampling pumps (Gilian GilAir 5; Sensidyne, St. Petersburg, FL, USA). The sampling pumps were calibrated by the Gilibrator calibrator in the field before and after each sampling. To validate the exposure levels measured by active sampling, a total of 71 workers in the 2 divisions of the 3 factories were randomly selected and personal passive diffusion monitors (3M Organic
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Table 1. General Characteristics of the Participants Printing division (n = 111) Variable Age (years) Education (years) Duration in current job (years) Working hours per day
Mean
SD
Mean
SD
p value
36.8 8.7 9.8 7.7
7.8 2.1 7.3 0.26
40.6 8.8 12.7 7.8
8.5 2.1 7.4 0.26
.001 .79 .005 .64
n
%
n
%
5 4 35 24 21 14
4.5 3.6 31.5 21.6 18.9 12.6
7 7 34 26 16 9
6.7 6.7 32.4 24.8 15.2 8.6
Poor general health status Alcohol drinking Smoking Poor sleep on previous night Recent frustrating events Current emotional problems
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Binding division (n = 105)
Vapor Monitors 3500; 3M Corporate Headquarters, St. Paul, MN, USA) were attached to the collar of their clothes for a whole work shift to measure time-weighted average personal solvents exposures. Temperature and humidity of the workshops were recorded simultaneously. Chemical analyses were done with gas chromatography (Shimadzu GC-9A; Shimadzu Corporation, Kyoto, Japan). Two representative compounds, toluene and n-hexane, were analyzed, as they were the most common toxic ingredients in the hydrocarbon solvents used in local printing factories. Total hydrocarbon (THC) was also assayed and used to estimate the intensity of mixed solvent exposure.
Data Analysis All data were double entered into computers independently by 2 research assistants using Epi-Info version 6.0 (CDC, Atlanta, GA, USA) and compared subsequently. Any mismatch would be corrected after checking with the original questionnaire and the test records. t tests and chi-square tests were used to compare the basic characteristics and relevant symptoms between the exposed group and the control group. The neurobehavioral test scores
.36 .48 .89 .58 .47 .34
were compared between the 2 groups by analysis of covariance, adjusting for potential confounding factors, including age and education. Multiple linear regression models were applied to assess the exposure-response relationships between the NCTB scores and the different exposure indices.
Results Table 1 presents the general characteristics of the workers stratified by working division. Workers in the printing division were younger and had worked for a shorter period of time in their current job than the workers in the binding division. There were no significant differences between these 2 divisions in other potential confounders. Table 2 shows the solvent levels in the 2 divisions. For active sampling, the levels in the printing divisions were much higher than those of the binding divisions. The passive sampling results were in line with the active sampling results. Figure 1 shows the correlations between the solvent levels measured by active sampling and passive sampling for the same subjects. The coefficient R for toluene, n-hexane, and THC was .72, .95, and .63, respectively (all p < .001).
Table 2. Solvent Levels in Printing and Binding Divisions (ppm) Printing division Solvent
Mean
Active sampling Toluene n-Hexane THC Personal sampling Toluene n-Hexane THC
n = 54 9.95 7.91 49.5 n = 43 6.73 3.54 36.8
Note. THC = total hydrocarbon.
Binding division
SD
Range
9.43 11.1 45.1
0.1–41.5 0.0–40.2 4.3–258.9
5.89 4.28 15.1
1.8–32.9 0.8–19.5 10.9–86.7
Mean n = 35 1.63 0.48 6.93 n = 28 1.39 0.30 4.69
SD
Range
p value
2.68 1.09 12.1
0.04–13.1 0.0–5.54 0–63.6
.001 .001 .001
1.41 0.51 6.74
0.03–5.6 0.0–1.7 0.0–31.4
.001 .001 .001
150
Song et al. Table 5 shows the associations between different exposure indices and NCTB test scores among all study subjects. The scores of Digit Symbol test, Pursuit Aiming Correct, Pursuit Aiming Incorrect, and Sum of Pursuit Aiming were inversely associated with various exposure indices. There were no significant associations between other NCTB test scores and the exposure indices (data not shown).
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Comment
Fig. 1. Correlations between solvent levels measured by active sampler and passive sampler.
The Profile of Mood States scores were not significantly different between the 2 divisions after adjusting for potential confounding factors (Table 3). Mean test performance of the 2 divisions is shown in Table 4. The scores of Digit Symbol test, Pursuit Aiming Correct, and Sum of Pursuit Aiming were significantly lower among the workers in the printing divisions. Further adjustment for potential confounders did not change the significant associations. There were no significant associations found between the 2 divisions for other tests.
Our results provide evidence to support an association between prolonged low-level exposure to organic solvents and adverse neurobehavioral effects among male printing workers in Hong Kong. Compared with workers in binding divisions, workers in printing divisions had lower performance scores of Digit Symbol test, Pursuit Aiming Correct, and Sum of Pursuit Aiming, which reflected decreased functions of perceptual-motor speed and motor steadiness.3 There were no significant associations for the POMS and other NCTB tests in the present study. Our findings were in line with most previous studies that showed that exposure to organic solvents were associated with increased risk of neurobehavioral dysfunction. Digit Symbol test, which is associated with both learning ability and perceptual motor function, has been reported to be associated with solvent exposure previously.7–10 Slower reaction times and impaired memory were also reported in carpet layers, painters, and car painters,6,8,26,27 who were exposed to solvents in their occupations. However, previous studies generally assessed the associations between the functions and the exposure to organic solvent mixtures rather than specific chemical components of the solvent. We measured the common components of solvent in the present study, including n-hexane, toluene, and total hydrocarbon, and found that these components were associated with the score of NCTB tests, which provided more specific evidences supporting the adverse neurobehavioral effects of exposure to low levels of organic solvents. The mechanisms of the damage of the central nervous system by organic solvents remain uncertain. Brain dopamine was once suggested as the target for solvent toxicity.28 Another hypothesis was the alteration of synaptosomal membrane function by solvents.29–31 Solvents may disrupt neurotransmitters or membrane integrity of neurons and cause impairment of axonal transmission. However, the exact mechanisms are not clear. Furthermore, as solvents generally contain many different chemical components, which components and how the components cause the effects are not clear.6 Further investigations on the mechanisms are warranted. Exposure assessment is not an easy task, but it is of utmost importance in many occupational epidemiological studies, and defining the exposure statuses of individual workers can be a real challenge. The present study used both active and passive sampling methods to confirm that the workers in printing divisions were exposed to low levels of organic solvents below the current threshold limit values used by the Hong Kong Government (50 ppm for toluene and 20 ppm for n-hexane).32 The active area sampling method enabled us to
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Table 3. Comparison of Scores of the Profile of Mood States Subscales Between the 2 Groups Printing division (n = 111)
Binding division (n = 105)
Subscale
Mean
SD
Adjusted mean
SD
Mean
SD
Adjusted mean
SD
p value
POMA POMC POMD POMF POMT POMV
49.3 48.4∗ 49.5 48.7 49.1 49.5
9.5 10.5 9.7 10.1 9.8 10.1
49.8 48.9 49.9 49.2 49.8 49.3
9.4 10.3 9.7 9.9 9.6 9.8
50.7 51.6 50.4 51.3 50.8 50.4
10.5 9.1 10.2 9.7 10.0 9.8
50.1 51.1 50.1 50.8 50.1 50.6
10.1 8.9 10.0 9.4 9.5 9.7
.81 .09 .88 .18 .82 .32
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Note. POMA = Profile of Mood States of Anger; POMC = POMS of Confusion; POMD = POMS of Depression; POMF = POMS of Fatigue; POMT = POMS of Tension; POMV = POMS of Vigor. ∗ Statistical significant at .05 level, compared with the control group before adjustment.
assess the occupational exposure for all workers in the workplaces and increased the sample size. The high correlation between results from active area sampling and passive personal sampling supported the validity of using active area sampling results to represent exposures of individual workers in our study. The mean duration in current job for the workers in printing divisions was 9.8 years, suggesting long-term exposures. Furthermore, the NCTB tests were performed at the beginning of work shifts to minimize acute effects of solvent exposures. The strengths of our study include the relatively large sample size, which enabled us to detect small neurobehavioral effects of low-level exposures to organic solvents. In addition, the relatively high response rate in our study could minimize the volunteer bias. Furthermore, we selected the workers in the binding divisions of the same factories as control groups, which could improve homogeneity between control groups and exposed groups in terms of socioeconomic
backgrounds, education, work/life habits, and other environmental factors and reduce possible confounding. However, there were limitations in our study. The cross-sectional nature of our study limited the interpretation of the causal relationship. Some potential confounding factors such as noise could not be taken into account in this cross-sectional study. Longitudinal prospective design with comprehensive information on potential confounding factors would be ideal but might be impractical, since the effect size is small and longterm follow up of a large cohort would be required. The assessment of exposure to solvents was limited to the inhalation route. Furthermore, the exposure indices in the present study were based on the measurements of a single working shift. There were no regular monitoring data on solvents exposure in the past 10 years for these 3 factories. The one-off measurement might not accurately represent the long-term exposure. More comprehensive investigations are required in the future.
Table 4. Comparison of Scores for Performance Tests Between the 2 Groups Printing division (n = 111)
Binding division (n = 105)
Subtest
Mean
SD
Adjusted mean
SD
Mean
SD
Adjusted mean
SD
p value
BVR DSPF DSPB DSPS DSY PAC PAINC PAS SAP SANP SRTM
50.6 49.5 50.1 49.8 48.2∗ 47.6∗ 49.4 47.9∗ 50.8 50.3 50.1
9.8 10.2 10.4 10.5 9.7 8.8 9.8 9.8 10.1 10.0 10.0
50.3 49.6 49.8 49.5 47.5 47.1 49.1 47.4 50.4 50.0 49.9
9.7 10.1 10.2 10.2 9.4 8.6 9.5 9.6 9.8 9.9 10.0
49.3 50.4 49.8 50.1 51.8 52.4 50.6 52.1 49.1 49.6 49.8
10.1 9.7 9.6 9.3 9.9 10.6 10.1 9.6 9.7 9.9 10.0
49.5 50.3 50.1 50.4 52.6 52.9 50.8 52.7 49.4 49.9 50.0
10.0 9.7 9.5 9.1 9.4 10.4 10.0 9.5 9.5 9.6 10.0
.54 .55 .83 .51 .01† .01† .23 .01† .44 .88 .90
Note. BVR = Benton Visual Retention; DSPF = Digit Span Forward; DSPB = Digit Span Backward; DSPS = Digit Span Sum; DSY = Digit Symbol; PAC = Pursuit Aiming Correct; PAINC = Pursuit Aiming Incorrect; PAS = Sum of Pursuit Aiming; SAP = Santa Ana (preferred hand); SANP = Santa Ana (nonpreferred hand); SRTM = Simple Reaction Time Mean. ∗ Statistical significant at .05 level, compared with the control group before adjustment. †p < .05 on analysis of covariance adjusting for potential confounding factors.
152
Song et al.
Table 5. Relationships Between Solvent Exposure Indices and NCTB Scores Among Male Printing Workers in Hong Kong (Adjusted for Age and Education) Exposure index Solvent
DSY β coefficient
PAC β coefficient
PAINC β coefficient
PAS β coefficient
Hexane Toluene THC
−.22 −.21∗ −.13∗
−.34∗ −.27∗ −.15∗
−.44∗ −.33∗ −.041
−.052 −.048 −.13∗
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Note. DSY = Digit Symbol; PAC = Pursuit Aiming Correct; PAINC = Pursuit Aiming Incorrect; PAS = Sum of Pursuit Aiming correct and incorrect; THC = total hydrocarbon. ∗ p < .05.
Our findings have important public health implications. The concentrations of solvent components in our study were less than the threshold limit values (TLVs) by the Hong Kong Government as well as those by American Conference of Industrial Hygienists (ACGIH). In Hong Kong, the TLVs for n-hexane and toluene are 20 and 50 ppm, respectively; for the ACGIH, the figures are 50 and 50 ppm, respectively.32,33 But adverse neurobehavioral effects were detected among the printing workers, suggesting that the present threshold limit values may not be sufficiently protective for those workers with long-term exposure to low-level organic solvents. Further actions such as adopting more stringent threshold limit values, improving ventilation, and increasing the awareness and knowledge of organic solvents among printing workers are recommended based on these findings. In summary, we found that long-term occupational exposure to low levels of organic solvents in air was associated with adverse neurobehavioral effects among male printing workers in Hong Kong. The present threshold limit values might not offer enough protection for the workers who have prolonged exposure to low levels of organic solvents. Further prevention actions should be considered for these workers.
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Neurobehavioral Effects of Occupational Exposure to Organic Solvents Among Male Printing Workers in Hong Kong a
b
b
Hong Song , Ignatius Tak-Sun Yu & Xiang Qian Lao a
Department of Preventive Medicine, School of Public Health, Sun Yat-Sen University, Guangzhou, China b
Division of Occupational and Environmental Health, School of Public Health and Primary Care, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China Accepted author version posted online: 01 Aug 2013.
Click for updates To cite this article: Hong Song, Ignatius Tak-Sun Yu & Xiang Qian Lao (2015) Neurobehavioral Effects of Occupational Exposure to Organic Solvents Among Male Printing Workers in Hong Kong, Archives of Environmental & Occupational Health, 70:3, 147-153, DOI: 10.1080/19338244.2013.828676 To link to this article: http://dx.doi.org/10.1080/19338244.2013.828676
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Archives of Environmental & Occupational Health (2015) 70, 147–153 C Taylor & Francis Group, LLC Copyright ISSN: 1933-8244 print / 2154-4700 online DOI: 10.1080/19338244.2013.828676
Neurobehavioral Effects of Occupational Exposure to Organic Solvents Among Male Printing Workers in Hong Kong HONG SONG1, IGNATIUS TAK-SUN YU2, and XIANG QIAN LAO2 1
Department of Preventive Medicine, School of Public Health, Sun Yat-Sen University, Guangzhou, China Division of Occupational and Environmental Health, School of Public Health and Primary Care, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China 2
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Received 6 March 2013, Accepted 25 June 2013
The objective of this study was to investigate the neurobehavioral effects of long-term occupational exposure to low levels of organic solvent among male printing workers in Hong Kong. A total of 115 printing workers exposed to organic solvents were recruited from the printing divisions of 3 printing factories, and 101 workers from the binding divisions of the same factories constituted the comparison group. Active and passive samplings were used to assess the occupational exposures to solvents. The World Health Organization Neurobehavioral Core Test Battery (WHO-NCTB) was applied to assess the neurobehavioral functions. Both active and passive sampling results showed that solvent levels were higher in the printing divisions than the binding divisions. The scores of Digit Symbol and Pursuit Aiming were poorer among workers in the printing divisions (all p values < .05). There were no significant differences found between the 2 divisions for other WHO-NCTB tests. The scores of Digit Symbol and Pursuit Aiming showed exposure-response relationship with various solvent exposure indices. Prolonged occupational exposure to low levels of organic solvents was associated with adverse neurobehavioral effects among male printing workers in Hong Kong. Keywords: neurobehavioral, organic solvents, printing
Organic solvents are widely used in painting, dry cleaning, printing, and adhesive manufacturing industries. It is well established that occupational exposure to high levels of organic solvent in air may impair the functions of the central nervous system.1–3 Threshold limit values have been set up in most developed countries, and high level exposures to solvents are expected to become less common. However, the neurotoxic effects of long-term, low-level exposure to organic solvents remain unclear.2 Some studies in the past several decades have shown that low-level exposures to organic solvents were associated with poor cognitive and motor performance,4–10 but the results were not always consistent.11–14 Several reviews have criticized the methodological flaws of the individual studies, including small sample size, selection bias, poor choice of matching controls, and the lack of standardized neuropsychological assessment methods.2,15–18 Therefore, although the
Address correspondence to Professor Ignatius Tak-Sun Yu, School of Public Health and Primary Care, 4th Floor, School of Public Health, Prince of Wales Hospital, Shatin, New Territories, Hong Kong. E-mail: [email protected]
volume of literature is great, the association between neurological dysfunction and prolonged low-level occupational exposure to solvents has remained a focus of research. The association between neurological dysfunction and prolonged low-level occupational exposure to solvents has remained a focus of research.17 Offset lithography printing and letterpress printing are the most widely used printing methods today. The ink, fountain solution, and cleaning materials used in the printing industry contain volatile organic compounds (VOCs), and printing workers are typically exposed to low levels of organic solvents in air during the operations. In the United States, the printing industry consisted of more than 36,000 establishments, with around 1 million employees and generated over $166 billion in sales in 2008.19 In Hong Kong, statistics for the year 2007 showed that 38,563 employees were working in 4,105 printing, publishing, and allied establishments.20 We have shown that exposure to mixtures of organic solvents increased the risk of neurological symptoms among printing workers in Hong Kong.21 However, data concerning neurobehavioral effects of low-level exposure to solvents are limited. We therefore investigated the chronic neurobehavioral effects of low-level occupational exposure to organic solvents among printing workers in Hong Kong.
148 Methods
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Setting and Participants An on-site investigation on the manufacture flow in local printing factories was conducted prior to the present study. Workers in printing divisions were generally exposed to mixed solvents on a daily basis, since they were involved in operating machines, assembling films, making plates, and cleaning equipment that used organic solvents. On the other hand, workers in binding divisions were generally not exposed to solvents, since their work only involved binding paper and packing products. We identified 3 printing factories of different employment sizes in Hong Kong and recruited workers from the printing divisions as the exposed group and workers in the binding divisions as the comparison group. In order to ensure consistent exposure levels over the past years for the workers, we selected the factories in which there were no substantial changes (including equipments and spaces) in the work environments over the past decade. The study was approved by Ethics Committee of the Chinese University of Hong Kong. Each participant signed a written consent prior to participation in the study. Previous studies have shown that the differences in the scores of Santa Ana Dexterity and Digit Symbol by solvent exposure status ranged from 4 to 9.7,22 We therefore estimated that a total of 200 workers would be sufficient to detect differences in the neurobehavioral test scores between the exposed and control groups in our study. Since the proportion of female workers was very low in the local printing industry,21 we only included male workers in the present study. Among the total 320 male workers in the 2 divisions of the 3 selected factories, 12 were excluded due to 1 or more of the following: aged over 55 years, taking sedative medication, and history of a disease that could affect neurobehavioral performance (eg, head injury with loss of consciousness). Of the remaining 308 workers eligible, 216 agreed to participate in the study and completed the interview and neurobehavioral tests (response rate: 70.1%), with 115 workers from the printing divisions and the other 101 from the binding divisions.
Song et al. The interviews and tests were conducted at the beginning of work shifts to ensure at least 12 hours without from solvent exposure at work, so that acute effects of solvent exposure on test performances could be minimized. Questionnaire The WHO -NCTB pretest interview questionnaire was adapted and applied in the present study, with questions covering general personal information, work histories, health statuses and living habits, history of diseases, current symptoms, nonoccupational exposures, and pretest conditions. Neurobehavioral Tests The WHO-NCTB was applied in the present study to assess neurobehavioral functions.23,24 The WHO-NCTB consists of the Profile of Mood States test (POMS), Digit Span test (DSP), Santa Ana Dexterity test (SA), Digit Symbol test (DSY), Benton Visual Retention test (BVR), Pursuit Aiming (PA), and Simple Reaction Time test (SRT). The tests were performed and interpreted strictly in accordance with the operational guide.23,24 All examiners received training before the formal investigation. The POMS test form was adapted using the local dialect, Cantonese. The form was translated into Cantonese based on the simple Chinese version, which had been used in China widely and proven to be of good validity.25 Before we used the Cantonese version in the field, the form were checked by 2 native Cantonese speakers and tested in another 2 Cantonese speakers to make sure that the description in Cantonese is appropriate and understandable. The neurobehavioral test scores were modified to standard scores in order to make the results easy to compare with other studies. In addition, standard scores could change the results to the same direction by reversing the Z score when larger scores indicated a negative effect. The standard scores were calculated by the following formula: Standard score = [(raw score minus mean) /standard deviation] × 10 + 50 The mean and standard deviation were computed from scores of all subjects.
Data Collection Each worker first signed a letter of consent to participate, and then completed a questionnaire through an interview by a trained investigator. The contents of the questionnaire were mainly based on the World Health Organization Neurobehavioral Core Test Battery (WHO-NCTB) annex pretest interview questionnaire. Neurobehavioral tests were then performed using the WHO-NCTB.23,24 The interview and tests were conducted in interview/test rooms set up especially for the study in each factory. The rooms were air conditioned, free from distracting noise, with adequate lighting and several sets of comfortable tables and chairs. Each NCTB test station was manned by a trained researcher, and each worker went through all the test stations in turn. All tests in each factory were completed within 2 to 3 days, during which production was pretty stable.
Exposure Assessment Solvent exposure was assessed using both active and passive sampling. For active sampling, the sampling locations were closed to the workstations where the workers operated. The height of the samplers was around 1.5 m, which is the height of the breathing zone of a typical worker. The sampling was performed for a work shift during the normal operation once, and time-weighted average was calculated. The sampling system consisted of the charcoal tube (800B; Kitagawa; Komyo Rikagaku Kogyo K.K., Kawasaki-City, Japan) and sampling pumps (Gilian GilAir 5; Sensidyne, St. Petersburg, FL, USA). The sampling pumps were calibrated by the Gilibrator calibrator in the field before and after each sampling. To validate the exposure levels measured by active sampling, a total of 71 workers in the 2 divisions of the 3 factories were randomly selected and personal passive diffusion monitors (3M Organic
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Table 1. General Characteristics of the Participants Printing division (n = 111) Variable Age (years) Education (years) Duration in current job (years) Working hours per day
Mean
SD
Mean
SD
p value
36.8 8.7 9.8 7.7
7.8 2.1 7.3 0.26
40.6 8.8 12.7 7.8
8.5 2.1 7.4 0.26
.001 .79 .005 .64
n
%
n
%
5 4 35 24 21 14
4.5 3.6 31.5 21.6 18.9 12.6
7 7 34 26 16 9
6.7 6.7 32.4 24.8 15.2 8.6
Poor general health status Alcohol drinking Smoking Poor sleep on previous night Recent frustrating events Current emotional problems
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Binding division (n = 105)
Vapor Monitors 3500; 3M Corporate Headquarters, St. Paul, MN, USA) were attached to the collar of their clothes for a whole work shift to measure time-weighted average personal solvents exposures. Temperature and humidity of the workshops were recorded simultaneously. Chemical analyses were done with gas chromatography (Shimadzu GC-9A; Shimadzu Corporation, Kyoto, Japan). Two representative compounds, toluene and n-hexane, were analyzed, as they were the most common toxic ingredients in the hydrocarbon solvents used in local printing factories. Total hydrocarbon (THC) was also assayed and used to estimate the intensity of mixed solvent exposure.
Data Analysis All data were double entered into computers independently by 2 research assistants using Epi-Info version 6.0 (CDC, Atlanta, GA, USA) and compared subsequently. Any mismatch would be corrected after checking with the original questionnaire and the test records. t tests and chi-square tests were used to compare the basic characteristics and relevant symptoms between the exposed group and the control group. The neurobehavioral test scores
.36 .48 .89 .58 .47 .34
were compared between the 2 groups by analysis of covariance, adjusting for potential confounding factors, including age and education. Multiple linear regression models were applied to assess the exposure-response relationships between the NCTB scores and the different exposure indices.
Results Table 1 presents the general characteristics of the workers stratified by working division. Workers in the printing division were younger and had worked for a shorter period of time in their current job than the workers in the binding division. There were no significant differences between these 2 divisions in other potential confounders. Table 2 shows the solvent levels in the 2 divisions. For active sampling, the levels in the printing divisions were much higher than those of the binding divisions. The passive sampling results were in line with the active sampling results. Figure 1 shows the correlations between the solvent levels measured by active sampling and passive sampling for the same subjects. The coefficient R for toluene, n-hexane, and THC was .72, .95, and .63, respectively (all p < .001).
Table 2. Solvent Levels in Printing and Binding Divisions (ppm) Printing division Solvent
Mean
Active sampling Toluene n-Hexane THC Personal sampling Toluene n-Hexane THC
n = 54 9.95 7.91 49.5 n = 43 6.73 3.54 36.8
Note. THC = total hydrocarbon.
Binding division
SD
Range
9.43 11.1 45.1
0.1–41.5 0.0–40.2 4.3–258.9
5.89 4.28 15.1
1.8–32.9 0.8–19.5 10.9–86.7
Mean n = 35 1.63 0.48 6.93 n = 28 1.39 0.30 4.69
SD
Range
p value
2.68 1.09 12.1
0.04–13.1 0.0–5.54 0–63.6
.001 .001 .001
1.41 0.51 6.74
0.03–5.6 0.0–1.7 0.0–31.4
.001 .001 .001
150
Song et al. Table 5 shows the associations between different exposure indices and NCTB test scores among all study subjects. The scores of Digit Symbol test, Pursuit Aiming Correct, Pursuit Aiming Incorrect, and Sum of Pursuit Aiming were inversely associated with various exposure indices. There were no significant associations between other NCTB test scores and the exposure indices (data not shown).
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Comment
Fig. 1. Correlations between solvent levels measured by active sampler and passive sampler.
The Profile of Mood States scores were not significantly different between the 2 divisions after adjusting for potential confounding factors (Table 3). Mean test performance of the 2 divisions is shown in Table 4. The scores of Digit Symbol test, Pursuit Aiming Correct, and Sum of Pursuit Aiming were significantly lower among the workers in the printing divisions. Further adjustment for potential confounders did not change the significant associations. There were no significant associations found between the 2 divisions for other tests.
Our results provide evidence to support an association between prolonged low-level exposure to organic solvents and adverse neurobehavioral effects among male printing workers in Hong Kong. Compared with workers in binding divisions, workers in printing divisions had lower performance scores of Digit Symbol test, Pursuit Aiming Correct, and Sum of Pursuit Aiming, which reflected decreased functions of perceptual-motor speed and motor steadiness.3 There were no significant associations for the POMS and other NCTB tests in the present study. Our findings were in line with most previous studies that showed that exposure to organic solvents were associated with increased risk of neurobehavioral dysfunction. Digit Symbol test, which is associated with both learning ability and perceptual motor function, has been reported to be associated with solvent exposure previously.7–10 Slower reaction times and impaired memory were also reported in carpet layers, painters, and car painters,6,8,26,27 who were exposed to solvents in their occupations. However, previous studies generally assessed the associations between the functions and the exposure to organic solvent mixtures rather than specific chemical components of the solvent. We measured the common components of solvent in the present study, including n-hexane, toluene, and total hydrocarbon, and found that these components were associated with the score of NCTB tests, which provided more specific evidences supporting the adverse neurobehavioral effects of exposure to low levels of organic solvents. The mechanisms of the damage of the central nervous system by organic solvents remain uncertain. Brain dopamine was once suggested as the target for solvent toxicity.28 Another hypothesis was the alteration of synaptosomal membrane function by solvents.29–31 Solvents may disrupt neurotransmitters or membrane integrity of neurons and cause impairment of axonal transmission. However, the exact mechanisms are not clear. Furthermore, as solvents generally contain many different chemical components, which components and how the components cause the effects are not clear.6 Further investigations on the mechanisms are warranted. Exposure assessment is not an easy task, but it is of utmost importance in many occupational epidemiological studies, and defining the exposure statuses of individual workers can be a real challenge. The present study used both active and passive sampling methods to confirm that the workers in printing divisions were exposed to low levels of organic solvents below the current threshold limit values used by the Hong Kong Government (50 ppm for toluene and 20 ppm for n-hexane).32 The active area sampling method enabled us to
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Table 3. Comparison of Scores of the Profile of Mood States Subscales Between the 2 Groups Printing division (n = 111)
Binding division (n = 105)
Subscale
Mean
SD
Adjusted mean
SD
Mean
SD
Adjusted mean
SD
p value
POMA POMC POMD POMF POMT POMV
49.3 48.4∗ 49.5 48.7 49.1 49.5
9.5 10.5 9.7 10.1 9.8 10.1
49.8 48.9 49.9 49.2 49.8 49.3
9.4 10.3 9.7 9.9 9.6 9.8
50.7 51.6 50.4 51.3 50.8 50.4
10.5 9.1 10.2 9.7 10.0 9.8
50.1 51.1 50.1 50.8 50.1 50.6
10.1 8.9 10.0 9.4 9.5 9.7
.81 .09 .88 .18 .82 .32
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Note. POMA = Profile of Mood States of Anger; POMC = POMS of Confusion; POMD = POMS of Depression; POMF = POMS of Fatigue; POMT = POMS of Tension; POMV = POMS of Vigor. ∗ Statistical significant at .05 level, compared with the control group before adjustment.
assess the occupational exposure for all workers in the workplaces and increased the sample size. The high correlation between results from active area sampling and passive personal sampling supported the validity of using active area sampling results to represent exposures of individual workers in our study. The mean duration in current job for the workers in printing divisions was 9.8 years, suggesting long-term exposures. Furthermore, the NCTB tests were performed at the beginning of work shifts to minimize acute effects of solvent exposures. The strengths of our study include the relatively large sample size, which enabled us to detect small neurobehavioral effects of low-level exposures to organic solvents. In addition, the relatively high response rate in our study could minimize the volunteer bias. Furthermore, we selected the workers in the binding divisions of the same factories as control groups, which could improve homogeneity between control groups and exposed groups in terms of socioeconomic
backgrounds, education, work/life habits, and other environmental factors and reduce possible confounding. However, there were limitations in our study. The cross-sectional nature of our study limited the interpretation of the causal relationship. Some potential confounding factors such as noise could not be taken into account in this cross-sectional study. Longitudinal prospective design with comprehensive information on potential confounding factors would be ideal but might be impractical, since the effect size is small and longterm follow up of a large cohort would be required. The assessment of exposure to solvents was limited to the inhalation route. Furthermore, the exposure indices in the present study were based on the measurements of a single working shift. There were no regular monitoring data on solvents exposure in the past 10 years for these 3 factories. The one-off measurement might not accurately represent the long-term exposure. More comprehensive investigations are required in the future.
Table 4. Comparison of Scores for Performance Tests Between the 2 Groups Printing division (n = 111)
Binding division (n = 105)
Subtest
Mean
SD
Adjusted mean
SD
Mean
SD
Adjusted mean
SD
p value
BVR DSPF DSPB DSPS DSY PAC PAINC PAS SAP SANP SRTM
50.6 49.5 50.1 49.8 48.2∗ 47.6∗ 49.4 47.9∗ 50.8 50.3 50.1
9.8 10.2 10.4 10.5 9.7 8.8 9.8 9.8 10.1 10.0 10.0
50.3 49.6 49.8 49.5 47.5 47.1 49.1 47.4 50.4 50.0 49.9
9.7 10.1 10.2 10.2 9.4 8.6 9.5 9.6 9.8 9.9 10.0
49.3 50.4 49.8 50.1 51.8 52.4 50.6 52.1 49.1 49.6 49.8
10.1 9.7 9.6 9.3 9.9 10.6 10.1 9.6 9.7 9.9 10.0
49.5 50.3 50.1 50.4 52.6 52.9 50.8 52.7 49.4 49.9 50.0
10.0 9.7 9.5 9.1 9.4 10.4 10.0 9.5 9.5 9.6 10.0
.54 .55 .83 .51 .01† .01† .23 .01† .44 .88 .90
Note. BVR = Benton Visual Retention; DSPF = Digit Span Forward; DSPB = Digit Span Backward; DSPS = Digit Span Sum; DSY = Digit Symbol; PAC = Pursuit Aiming Correct; PAINC = Pursuit Aiming Incorrect; PAS = Sum of Pursuit Aiming; SAP = Santa Ana (preferred hand); SANP = Santa Ana (nonpreferred hand); SRTM = Simple Reaction Time Mean. ∗ Statistical significant at .05 level, compared with the control group before adjustment. †p < .05 on analysis of covariance adjusting for potential confounding factors.
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Song et al.
Table 5. Relationships Between Solvent Exposure Indices and NCTB Scores Among Male Printing Workers in Hong Kong (Adjusted for Age and Education) Exposure index Solvent
DSY β coefficient
PAC β coefficient
PAINC β coefficient
PAS β coefficient
Hexane Toluene THC
−.22 −.21∗ −.13∗
−.34∗ −.27∗ −.15∗
−.44∗ −.33∗ −.041
−.052 −.048 −.13∗
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Note. DSY = Digit Symbol; PAC = Pursuit Aiming Correct; PAINC = Pursuit Aiming Incorrect; PAS = Sum of Pursuit Aiming correct and incorrect; THC = total hydrocarbon. ∗ p < .05.
Our findings have important public health implications. The concentrations of solvent components in our study were less than the threshold limit values (TLVs) by the Hong Kong Government as well as those by American Conference of Industrial Hygienists (ACGIH). In Hong Kong, the TLVs for n-hexane and toluene are 20 and 50 ppm, respectively; for the ACGIH, the figures are 50 and 50 ppm, respectively.32,33 But adverse neurobehavioral effects were detected among the printing workers, suggesting that the present threshold limit values may not be sufficiently protective for those workers with long-term exposure to low-level organic solvents. Further actions such as adopting more stringent threshold limit values, improving ventilation, and increasing the awareness and knowledge of organic solvents among printing workers are recommended based on these findings. In summary, we found that long-term occupational exposure to low levels of organic solvents in air was associated with adverse neurobehavioral effects among male printing workers in Hong Kong. The present threshold limit values might not offer enough protection for the workers who have prolonged exposure to low levels of organic solvents. Further prevention actions should be considered for these workers.
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