|Year : 2019 | Volume
| Issue : 2 | Page : 68-72
Association of musculoskeletal disorders and inflammation markers in workers exposed to lead (Pb) from Pb-battery manufacturing plant
Kalahasthi Ravibabu1, Bhavani Shankara Bagepally2, Tapu Barman3
1 Department of Biochemistry, Regional Occupational Health Centre (Southern) Bengaluru, ICMR Complex, Poojanahalli Road, Kannamangala Post, Devanahalli, Bengaluru, Karnataka, India
2 Department of NCD, National Institute of Epidemiology (ICMR), Second Main Road, Tamil Nadu Housing Board, Ayapakkam, Near Ambattur, Chennai, Tamil Nadu, India
3 Department of Bacteriology, National Institute of Cholera and Enteric Diseases, P-33, C.I.T. Road, Scheme XM, Beleghata, Kolkata, West Bengal, India
|Date of Submission||05-Sep-2018|
|Date of Acceptance||18-Mar-2019|
|Date of Web Publication||25-Sep-2019|
Dr. Kalahasthi Ravibabu
Department of Biochemistry, Regional Occupational Health Centre (Southern), ICMR Complex, Poojanahalli Road, Kannamangala Post Devanahalli, Bengaluru - 562 110, Karnataka
Source of Support: None, Conflict of Interest: None
Background: Lead (Pb) deposits in the skeletal system on chronic exposure and releases to circulation over a period. The musculoskeletal disorders (MSDs) are associated with enhanced expression of inflammation. The combination of Pb-exposure and MSDs induced inflammation was not attempted. Objective: This study was conducted to examine the association between MSDs and inflammatory markers in workers exposed to Pb from Pb-battery plant. Material and Methods: In a case-control study design, the study enrolled 176 male Pb-exposed workers as study subjects and 80 healthy workers with no occupational exposure to Pb as control subjects. The Nordic musculoskeletal questionnaire was used to assess the MSDs. From the blood sample, blood lead level (BLL) and High Sensitivity C-reactive protein (Hs-CRP) were estimated as markers of Pb-exposure and Inflammatory marker respectively. The BLL was estimated by flame atomic absorption spectrometric method and the Hs-CRP by using a diagnostic kit method. Results: Significantly high proportions of MSDs were noted in study subjects as compared to controls. The MSDs identified in the study subjects were at low back (33%) followed by knee (26%), shoulders (16%), neck (14%), ankle/foot (11%), wrist/hand (10%), elbows (8%), upper back (7%), and hips/thighs (5%). The significant association between Pb-exposure and MSDs among study subjects was mainly noted in low back and ankle/foot. Also, significantly high serum Hs-CRP levels were noted among study subjects with ankle/foot MSDs. Conclusion: Pb-exposure and inflammatory markers were significantly associated with lower limbs of MSDs.
Keywords: Blood lead levels, inflammatory markers, lead exposure, musculoskeletal disorders, Pb-battery workers
|How to cite this article:|
Ravibabu K, Bagepally BS, Barman T. Association of musculoskeletal disorders and inflammation markers in workers exposed to lead (Pb) from Pb-battery manufacturing plant. Indian J Occup Environ Med 2019;23:68-72
|How to cite this URL:|
Ravibabu K, Bagepally BS, Barman T. Association of musculoskeletal disorders and inflammation markers in workers exposed to lead (Pb) from Pb-battery manufacturing plant. Indian J Occup Environ Med [serial online] 2019 [cited 2020 Aug 14];23:68-72. Available from: http://www.ijoem.com/text.asp?2019/23/2/68/267753
| Introduction|| |
Manufacturing of Lead (Pb) batteries is involved in the preparation of lead oxide, grid casting, pasting, plate cutting, formation, charging, and assembly. The chemicals used in these processes are hazardous in nature; they comprise of lead oxide (PbO2), spongy lead (Pb), and sulfuric acid (H2 SO4). Pb can enter the bodies of workers through inhalation and ingestion. Inhalation is the primary route of exposure in Pb-related occupations. In the body, Pb accumulates in erythrocytes, soft tissues (brain, kidney, and bone marrow), and mineralized tissue (bone, teeth). Literature states that workers exposed to Pb form Pb-battery manufacturing plant have reported the disturbances in epigenetic status, oxidative DNA damage, altered reticulocyte count, oxidative stress, biogenic amino acids with neurobehavioral changes, gene polymorphisms of ALAD, glutathione peroxidase (GPx), paraoxonase and metallothionein-4 activities ,,, and calcium metabolism with bone mineral density. Pb also affects several body systems, which include blood pressure, ocular changes, coagulation, osteoporosis risk  poor dental health, hearing loss  cardiovascular, neuropathy, renal, hepatic , and reproductive  abnormalities.
Musculoskeletal disorders (MSDs) are work-related ailments. It affects multiple body parts at the back, neck, shoulders, and upper and lower limbs. Physical and organizational hazards are the significant contributors of work-related MSDs. The causes of MSDs include the handling of loads, repetitive or forceful movements, awkward and static postures, vibration, poor lighting or cold working environments, and prolonged sitting or standing in the same position. Musculoskeletal components such as motor skills, bones growth and development, dentition, fracture healing, bone density, and joint maintains are susceptible to Pb. Kuruvilla et al. reported the prevalence of backache, muscular exhaustibility, myalgia, and paresthesia in workers from printing and lead-battery plant. It was reported that the MSD morbidities among Pb-battery manufacturing workers were significantly associated with odds of blood lead levels (BLLs). A recent study reported high prevalence of pain in limbs, weakness of limbs, and numbness of limbs among these Pb-workers. Also, in severe Pb-poisoning generalized weakness predominates in proximal limbs. It is well documented in the literature that the Pb-exposure enhances the expression of inflammation., Pb-induced inflammation causes the disorders of various organs such as respiratory, neurologic, digestive, cardiovascular, and urinary diseases ; however, there is limited literature on musculoskeletal systems. It has been observed that the farmers with MSD had altered plasma levels of protein biomarkers compared to the referents, indicating that farmers with MSD had more systemic inflammation. Healthy females with work-related neck/shoulder pain showed higher serum concentrations of CRP than controls, and the levels of CRP were correlated to pain intensity. The review of literature suggests that the Pb-exposure and the presence of MSDs are associated with inflammation. However, there is limited literature about the association between the Pb-exposure and MSDs along with inflammatory biomarkers. This study is intended to find out the association between MSDs of different parts of body regions and inflammatory markers in workers exposed to Pb from Pb-battery manufacturing plant.
| Materials and Methods|| |
The study used case-control study design. The workers engaged in Pb-battery manufacturing plant and exposed to Pb with >2 years were considered as study subjects.
The study involved a total of 256 male subjects, including both study subjects and controls. The study group consisted of 176 workers, who were working in Pb-battery manufacturing plant located in Tamilnadu, India. Eighty office workers with no occupational exposure to Pb were considered as a control group. The control subjects were matched for age and the socioeconomic status of study group. The institutional ethical committee approved the study. Informed written consent was obtained from each of the subject before participation in the study. Demographic details, work history, and habits of the subjects were obtained through a validated questionnaire.
Blood sample collection
From each subject 4 ml (2 ml in heparin tubes + 2 ml in plain tubes) of whole blood was collected. 2 ml of heparinised blood was used for the determination of BLL. 2 ml of whole blood sample was collected in plain tubes, centrifuged at 4000 RPM for 10 min at 4°C for the separation of serum and red blood cells. The serum samples were used for the assessment of inflammatory markers.
The BLLs were measured as mentioned previously in Barman et al. Briefly, in this method, 2 ml of whole blood sample was digested by a microwave digestion system (ETHOS-D, Italy) with 2 ml of nitric acid (HNO3) and 0.2 ml of hydrogen peroxide (H2O2). The digested samples were made up to 5 ml using distilled water and centrifuged. The BLL was measured by an atomic absorption spectrophotometer (GBC Avanta, Australia).
Inflammatory and anthropometry
Inflammatory and anthropometry assessment was performed using the guidelines of Soeters et al. (i) Anthropometry (body weight, height, and body mass index) and (ii) measurement of inflammatory activity (albumin, hemoglobin, and Hs-C-reactive protein).
Body mass index
BMI was calculated by using subject's weight (Kg) by squared height (m) and expressed as Kg/m2.
The serum albumin concentration was measured by using bromocresol green method of Doumas et al. In this method, albumin in a buffered solution reacts with the anionic bromocresol green dye and gives a green color that was measured at 628 nm. The intensity of green color was directly proportional to the concentration of albumin present in the sample. The results were expressed as g/dL of sample.
The hemoglobin content in samples was measured by using the method developed by Drabkin and Austin. In this method, 20 μL of blood is mixed with 5 mL of Drabkin's solution that contains ferricyanide and cyanide. The ferricyanide oxidizes hemoglobin into methemoglobin. Methemoglobin then unites with the cyanide to form cyanmethemoglobin and which produces a color that is measured at 540 nm using a colorimeter (Elico, CL-223). The level of hemoglobin is expressed as g/dL.
Serum high sensitivity C - reactive protein (Hs-CRP)
The concentration of Hs-CRP in serum was determined using latex turbidimetric immunoassay. Latex particles coated with purified anti-CRP, when allowed to react with samples containing CRP agglutinate causing a change in absorbance. The change of absorbance depends on the concentration of CRP and is determined by comparing it with the known concentration of the calibrator. The concentration of CRP in the samples was expressed as mg/L. The detection limit of the method is 1 mg/L and measuring range is 1−160 mg/L.
Musculoskeletal disorders (MSDs)
The Nordic musculoskeletal questionnaire (NMQ) was used to identify the MSDs among study and control subjects. This questionnaire assesses the frequency of symptoms in all parts of the body. Choi et al. validated the questionnaire of NMQ for assessing the MSDs. Validated data of NMQ were found to have the sensitivity of 73.9%, specificity of 68%, positive predict value of 72.6%, negative predictive value of 69.5%, and kappa coefficient is 0.42.
Data analysis was performed using SPSS version 16.0 (SPSS). The data were evaluated using the obtained mean and SD and compared with Student's t-test between study subjects and controls. The Chi-squared test was used to compare the MSDs distribution among study and control group. Spearmen correlation coefficient (r) test was used to find out the association between BLLs and inflammatory markers. The differences of BLLs and inflammatory in workers with and without MSDs were computed by using nonparametric Mann-Whitney U test. P value of < 0.05 was considered statistically significant.
| Results|| |
The demographic details of study and control subjects were presented in [Table 1]. The study parameters such as age, blood pressure (SBP and DBP), frequency distribution of alcohol consumption, and smoking habits did not differ between study and controls. Significantly elevated BLLs were noted in study subjects as compared to controls. The frequency distribution of elevated BLLs among study subjects were reported as per the set guidelines of American Conference of Governmental Industrial Hygienist-Biological Exposure Index.
The frequency of MSDs in the study and control subjects at different body regions were tabulated in [Table 2]. Significantly high proportion of MSDs was observed in study subjects as compared to controls. In study subjects, the highest proportion of MSD condition was identified at lower back ache (33%), followed by the knee (26%), shoulders (16%), neck (14%), ankle/feet (11%), wrist/hand (10%), elbows (8%), upper back (7%), and hips/thighs (5%).
|Table 2: Musculoskeletal disorders in study and control subjects according to body regions|
Click here to view
The means and standard deviation values of BLLs and inflammatory biomarkers in Pb-exposed workers with or without MSDs were presented in [Table 3]. Significantly higher BLLs were observed among subjects with MSDs at upper back, lower back, and ankle/feet as compared to without MSDs. Higher serum Hs-CRP was observed among subjects with ankle/feet MSD as compared to subjects without MSD.
|Table 3: Blood lead levels and inflammatory markers in subjects with and without MSD|
Click here to view
The results of spearmen correlation coefficients (r) between BLLS and inflammatory markers among total subjects were presented in [Table 4]. A significant positive correlation was noticed between BLLs with Hb% and Hs C-reactive protein.
|Table 4: Spearmen correlation coefficients (r) between blood lead levels and inflammatory markers|
Click here to view
| Discussion|| |
This study assessed the association between MSDs of different body regions and inflammatory markers in workers exposed to Pb from Pb-battery manufacturing plant. The study observed higher proportions of MSDs in Pb-exposed workers. Significantly higher BLLs were observed among subjects with MSD at upper-back, lower-back, and ankle/feet as compared to without MSDs.
The current literature reports that generalized weakness predominates in proximal limbs in severe Pb-poisoning cases, However, other studies observed backache, muscular exhaustibility, myalgia, and paresthesia in printers and Pb-battery workers. This study also reiterates the high proportion of MSDs among chronic Pb-exposed workers. The MSDs conditions identified in the study subjects were at lower back (33%), followed by knee (26%), shoulders (16%), neck (14%), ankle/feet (11%), wrist/hand (10%), elbows (8%), upper back (7%), and hips/thighs (5%). The literature suggests that the Pb induces an osteoarthritis-like phenotype in articular chondrocytes through the disruption of TGF-β signaling leads disruption normal chondrocyte phenotype. Kalahasthi et al. reported that the odds ratio of BLLs was significantly associated with MSDs in workers from Pb-battery plant. In this study, the Pb-exposure in the form of elevated BLLs was significantly associated with workers who had MSDs at upper and lower back and ankle and foot. Similar observations were also reported in a recent study with high prevalence of pain in limbs, weakness of limbs, and numbness of limbs in Pb-battery workers. The numbness in limbs was significantly associated with BLLs. In this study, in addition to echoing of that finding, we observed that the workers, who had ankle/foot problems, were significantly associated with BLLs.
This study observed higher serum Hs-CRP among subjects with ankle/feet MSD as compared to subjects without MSD. The current literature abridges that the Pb-exposure enhances the expression of inflammation factors and causes the disorders of various organs such as respiratory, neurologic, digestive, cardiovascular, and urinary diseases.,, Several evidence of literature from MSD research point out that MSD is associated with higher inflammatory markers, such as farmers with MSD had altered plasma levels of protein biomarkers compared to the referents, suggesting that farmers with MSD had more systemic inflammation. Healthy females with work-related neck/shoulder pain showed higher serum concentrations of CRP than controls, and the levels of CRP were correlated to pain intensity. Thus, most of the studies report that the Pb-exposure and the presence of MSD are associated with inflammation expressions. In this study, we report the association between MSDs, more specifically directed toward lower-limb MSDs and inflammatory markers in workers exposed to Pb from Pb-battery plant. In addition, we also report that higher levels of serum Hs-CRP were noted in subjects with ankle/feet MSD as compared to subjects without MSD. Further, the levels of inflammatory markers were positively associated with BLLs, and a significant association was noted in Hb% and serum Hs-CRP. Pb-exposure and inflammatory marker were significantly associated with lower limbs of MSDs. In conclusion, these findings of higher MSDs in lower limb as well as its significant association with high inflammatory markers suggest that the lower limbs are more influenced by occupational Pb-exposure associated with MSDs. However, more specific studies are warranted to confirm these findings in different occupational Pb-exposed situations.
The authors are thankful to the Director, National Institute of Occupational Health, ICMR, for his suggestions and encouragement during the study. The authors extending thanks to the study subjects, who are enthusiastically participating in the study.
Financial support and sponsorship
ICMR, New Delhi.
Conflicts of interest
There are no conflicts of interest.
| References|| |
Devoz PP, Gomes WR, De Araujo ML, Ribeiro D, Pedron T, GreggiAntunes LM, et al
. Lead (Pb) exposure induces disturbances in epigenetic status in workers exposed to this metal. J Toxicol Environ Health A 2017;80:1098-105.
Pawlas N, Olewinska E, Markiewicz-Gorka I, Kozłowska A, Januszewska L, Lundh T, et al
. Oxidative damage of DNA in subjects occupationally exposed to lead. Adv Clin Exp 2017;26:939-45.
Kalahasthi R, Barman T. Effect of lead exposure on the status of reticulocyte count indices among workers from lead battery manufacturing plant. Toxicol Res 2016;32:281-7.
Ghanwat GH, Patil AJ, Patil JA, Kshirsagar MS, Sontakke A, Ayachit RK. Biochemical effects of lead exposure on oxidative stress and antioxidant status of battery manufacturing workers of Western Maharashtra, India. J Basic Clin Physiol Pharmacol 2016;27:141-6.
Ravibabu K, Barman T, Rajmohan HR. Serum neuron-specific enolase, biogenic amino-acids and neurobehavioral function in lead-exposed workers from lead-acid battery manufacturing process. Int J Occup Environ Med 2015;6:50-7.
Da Cunha Martins AJ, MazzaronBarcelos GR, Jacob Ferreira AL, de Souza MF, de SyllosColus IM, Antunes LM, et al
. Effects of lead exposure and genetic polymorphisms on ALAD and GPx activities in brazilian battery workers. J Toxicol Environ Health A 2015;78:1073-81.
Kamal M, Fathy MM, Taher E, Hasan M, Tolba M. Assessment of the role of paraoxonase gene polymorphism (Q192R) and paraoxonase activity in the susceptibility to atherosclerosis among lead-exposed workers. Ann Saudi Med 2011;31:481-7.
] [Full text]
Chen HI, Chiu YW, Hsu YK, Li WF, Chen YC, Chuang HY. The association of metallothionein-4 gene polymorphism and renal function in long-term lead-exposed workers. Biol Trace Elem Res 2010;137:55-62.
Dongre NN, Suryakar AN, Patil AJ, Hundekari IA, Devarnavadagi BB. Biochemical effects of lead exposure on battery manufacture workers with reference to blood pressure, calcium metabolism and bone mineral density. Indian J Clin Biochem 2013;28:65-70.
Taheri L, Sadeghi M, Sanei H, Rabiei K, Arabzadeh S, Golshahi J, et al
. The relation between occupational exposure to lead and blood pressure among employed normotensive men. J Res Med Sci 2014;19:490-4.
Ekinci M, Ceylan E, Caǧatay HH, Keleş S, Altınkaynak H, Kartal B, et al
. Occupational exposure to lead decreases macular, choroidal, and retinal nerve fiber layer thickness in industrial battery workers. Curr Eye Res 2014;39:853-8.
Barman T, Kalahasthi R, Rajmohan HR. Effects of lead exposure on the status of platelet indices in workers involved in a lead-acid battery manufacturing plant. J Expo Sci Environ Epidemiol 2014;24:629-33.
Raafat BM, Hassan NS, Aziz SW. Bone mineral density (BMD) and osteoporosis risk factor in Egyptian male and female battery manufacturing workers. Toxicol Ind Health 2012;28:245-52.
Suyama Y, Takaku S, Okawa Y, Matsukubo T. Dental erosion in workers exposed to sulfuric acid in lead storage battery manufacturing facility. Bull Tokyo Dent Coll 2010;51:77-83.
Ghiasvand M, Mohammadi S, Roth B, Ranjbar M. The relationship between occupational exposure to lead and hearing loss in a cross-sectional survey of iranian workers. Front Public Health 2016;4:19.
Ghiasvand M, Aghakhani K, Salimi A, Kumar R. Ischemic heart disease risk factors in lead exposed workers: Research study. J Occup Med Toxicol 2013;8:11.
Misra UK, Kalita J. Toxic neuropathies. Neurol India 2009;57:697-705.
] [Full text]
Wang VS, Lee MT, Chiou JY, Guu CF, Wu CC, Wu TN, et al
. Relationship between blood lead levels and renal function in lead battery workers. Int Arch OccupEnviron Health 2002;75:569-75.
Dadpour B, Afshari R, Mousavi SR, Kianoush S, Keramati MR, Moradi VA, et al
. Clinical and laboratory findings of lead hepatotoxicity in the workers of a car battery manufacturing factory. Iranian J Toxicology 2016;10:1-6.
Haghighi KS, Aminian O, Chavoshi F, Bahaedini LS, Soltani S, Najarkolaei FR. Relationship between blood lead level and male reproductive hormones in male lead exposed workers of a battery factory: A cross-sectional study. Iran J Reprod Med 2013;11:673-6.
22 Holz JE, Beier E, Puzas JE. Effects of lead deposition on the musculoskeletal system. Curr Top Toxicol 2012;8:1-12.
Kuruvilla A, Pillay VV, Adhikari P, Venkatesh T, Chakrapani M, Jayaprakash Rao HT, et al
. Clinical manifestations of lead workers of Mangalore, India. Toxicol Ind Health 2006;22:405-13.
Kalahasthi RB, Barman T, Rajmohan HR. The relationship between blood lead levels and morbidities among workers employed in a factory manufacturing lead–acid storage battery. Int J Environ Health Res 2014;24:246-55.
Singamsetty B, Gollapudi PK. A study on health profile of workers in a battery factory with reference to lead toxicity: Six months study. Int J Commun Med Public Health 2017;4:1519-25.
Srisuma S, Lavonas EJ, Wananukul W. Proximal muscle weakness in severe lead poisoning from retained bullet fragments. Clin Toxicol 2015; 53: 586-7.
Metryka E, Chibowska K, Gutowska I, Falkowska A, Kupnicka P, Barczak K, et al
. Lead (Pb) exposure enhances expression of factors associated with inflammation. Int J Mol Sci 2018;19. pii: E1813. doi: 10.3390/ijms19061813.
Machon-Grecka A, Dobrakowski M, Boroń M, Lisowska G, Kasperczyk A, Kasperczy KS. The influence of occupational chronic lead exposure on the levels of selectedpro-inflammatory cytokines and angiogenic factors. Hum Exp Toxicol 2017;36:467-73.
Boskabady M, Marefati N, Farkhondeh T, Shakeri F, Farshbaf A, Boskabady MH. The effect of environmental lead exposure on human health and the contribution of inflammatory mechanisms, a review. Environ Int 2018;120:404-20.
Ghafouri B, Carlsson A, Holmberg S, Thelin A, Tagesson C. Biomarkers of systemic inflammation in farmers with musculoskeletal disorders; a plasma proteomic study. BMC Musculoskelet Disord 2016;17:206.
Matute Wilander A, Karedal M, Axmon A, Nordander C. Inflammatory biomarkers in serum in subjects with and without work related neck/shoulder complaints. BMC Musculoskelet Disord 2014;15:103.
Soeters PB, Reijven PL, van Bokhorst-de van der Schueren MA, Schols JM, Halfens RJ, Meijers JM, et al
. A rational approach to nutritional assessment. Clin Nutr 2008;27:706-16.
Doumas BT, Watson WA, Biggs HG. Albumin standards and measurement of serum albumin with bormocresol green. Clin Chim Acta 1971;31:87-96.
Drabkin DL, Austin JH, Spectrophotometric studies: I. Spectrophotometric constants for common hemoglobin derivatives in human, dog and rabbit blood. J Biol Chem 1932;98:719-33.
Crawford JO. The Nordic musculoskeletal questionnaire. Occup Med (Lond) 2007;57:300-1.
Choi WJ, Sung NJ, Kang YJ, Han SH. Validity of NIOSH- and nordic-style questionnaires in the screening and surveillance of neck and upper extremity work-related musculoskeletal disorders. Korean J Occup Environ Med 2008;20:205-14.
Holz JD, Beier E, Sheu T-J, Ubayawardena R, Wang M, Sampson ER, et al
. Lead induces an osteoarthritis-like phenotype in articular chondrocytes through disruption of TGF-β signaling. J Orthop Res 2012;30:1760-6.
Ahmad SA, Khan MH, Khandker S, Sarwar AF, Yasmin N, Faruquee MH, et al
. Blood lead levels and health problems of lead acid battery workers in Bangladesh. The Scientific World Journal 2014:974104. doi: 10.1155/2014/974104.eCollection 2014.
[Table 1], [Table 2], [Table 3], [Table 4]