Removal Statement

The production of carbon black (CB) has been considered as one of the top 50 industrial chemicals manufactured worldwide. Working in CB manufacturing process might pose a cardiovascular risk. This ...


Introduction
Carbon black (CB) refers to material consisting of more than 85% elemental carbon in the form of nearspherical colloidal particles and coalesced particle aggregates of colloidal size obtained by partial combustion or thermal decomposition of hydrocarbons. It is a fine black powder, used mainly as a reinforcing agent in tire industry, rubber production, inks and paints production. The worldwide production of CB has been considered as one of the top 50 industrial chemicals manufactured worldwide [1].
Exposure to CB has been linked to cardiac and ventricular arrhythmia, ST-segment depression, decreased flow-mediated vascular reactivity, lowered heart rate variability, and increased cardiovascular mortality [2]. Working in CB manufacturing process poses a cardiovascular risk for several reasons. Inhalation of CB suspended particulate matter (SPM) may occur during the production, processing, distribution, storage, and use of CB. Epidemiological studies of exposure to airborne particulates have reported associations with a variety of cardiovascular effects including myocardial infarction and ischemic heart disease [3,4]. In addition, oil furnace process accounts for over 95% of CB world production; during the manufacturing process and as a result of incomplete combustion of hydrocarbon feedstock oil at high temperature, a lot of gaseous byproducts and pollutants such as polycyclic aromatic hydrocarbons (PAHs) [5].
Absorption of particulate polycyclic organic material and PAHs during CB manufacture, could affect the heart directly as they accumulate in the brain causing cardiovascular modulation and autonomic cardiac dysfunction. PAHs may indirectly dysregulate autonomic cardiac function by promoting oxidative stress pathways via induction of lipid peroxidation, which can lead to stimulation of sympathetic supply, inhibition of parasympathetic supply, activation of apoptosis in cardiac cells, ventricular dysfunction and heart failure [6][7][8]. Other combustion byproducts that pose a cardiovascular risk include carbon monoxide, and sulfur dioxide [5]. Additionally, workers in CB industry are exposed to volatile organic compounds, noise, heat, job stress, and shiftwork. These exposures are, likewise, associated with cardiovascular risk [9][10][11][12][13][14].
In Egypt, adverse cardiac effects among workers in CB industry were reported in El Okda and Maraghy study [2014,2]. Estimation of risk of developing CHD among workers would be a crucial step for primary prevention, This study was conducted to assess 10year CHD risk among workers in CB manufacturing process.

Study design and setting
A cross-sectional comparative study was conducted in a CB factory located in Alexandria city. The factory has eight departments namely production, processing, filling, storage, maintenance, administration, sales and marketing departments with a weekly 40 hours worked per worker. The factory's annual production of CB mounts to 50,000 tons per year; that goes into everything from tires, other rubber goods, plastics, inks, dyes and paints. The field work of the study was conducted over a 3-month period from February through April, 2019.

Participants
Study population comprised male workers with service of duration of at least 2 years [3] and not using cholesterol lowering drugs. Only 15 women were employed in the CB factory; these women were excluded as their number would be insufficient for statistical analysis.
A total of 342 workers were registered workers in this factory during the period of the study. Male workers (n = 327) were invited to participate in the study; those who agreed to participate were 277 male workers, with an overall response rate (without regard to eligibility) of 84.70%. They were screened for eligibility based on inclusion and exclusion criteria. Only eligible workers were included in this study (n = 271). Workers included in this study were distributed into two groups [2]: a) exposed group: that represent workers in the departments of production, processing, filling, storage and maintenance departments. This group served as the inference population; and b) unexposed group: workers at nonmanufacturing departments in the same factory including administration, sales, and marketing departments. This group served as a comparison group.

Study tools
All participants were subjected to the following: Interview questionnaire was conducted to collect data about workers' sociodemographic data (age, marital status and residence); medical history: history of diabetes mellitus and hypertension based on a previous medical diagnosis or receiving specific medications; occupational history (nature of work, duration of employment); family history of CHD; and smoking habit: a worker was classified as: i) never smoker: a worker who has never smoked or who has smoked less than 100 cigarettes in his lifetime, and ii) smoker: a worker who has smoked more than 100 cigarettes in his lifetime and who currently smokes cigarettes (current smoker), or who had quit smoking at the time of interview (former smoker) [15].
Blood pressure measurement: using Korotkoff technique following the standard procedure. Hypertension was defined as systolic blood pressure higher or equal to 140 mmHg or diastolic blood pressure higher or equal to 90 mmHg [16].
Anthropometric measurements: height and weight were measured following the standard procedure. Body mass index (BMI) was calculated as weight in kilograms divided by squared height in meters (kg/ m 2 ) [16].
Calculation of Framingham risk score (FRS); 10year CHD%: It is a universal validated (last validated in 2018), and simple tool for estimation of risk level of developing CHD over the next 10 years [18]; based on the Framingham Heart Study [19]. FRS has been used to measure CVD risk in the general population, as well as working population, for example, it has been used for prediction of CVD risk among office workers [20] and rural workers [21]. In addition, the effect of workrelated variables on FRS prediction of CVD was evaluated [22], and FRS was used as a clinical tool of assessment of fitness for work [23].
In the present study, FRS sheet (points system) was used to estimate the 10-year of CHD by summing points for the following measurable factors: age, gender, total cholesterol (mg/dl), smoking status (yes/no), high-density lipoprotein (HDL) (mg/dl), and systolic blood pressure (mmHg) [24]. Based on FRS, workers were categorized into: i) workers with low CHD-risk (10-year risk% of < 10); ii) workers with intermediate CHD-risk (10-year risk percentage ranged from 10 to 20); and iii) workers with high CHD-risk (10-year risk percentage of >20) [19,24].

Statistical analysis of the data
The SPSS software program version 20 (IBM Corp. Released 2011. IBM SPSS Statistics for Mac, Armonk, NY, USA) was used for data entry and analysis. Data were presented using frequency, percentages, mean, and standard deviation. Exposed and unexposed workers were compared regarding potential risk factors for CHD using parametric and non-parametric tests based on the variable type and its distribution. The Student t-test, Mann Whitney test, Chi-square test and Fisher's exact test were the used test of significance.
By using FRS, the 10-year CHD risk percent (dependent variable) is estimated based on six determinants of the risk of CHD (independent variables) and their effect in relation to each other was uniformly assessed for all workers, thus, it would be inappropriate to run a multivariate regression model including the same risk factors. Accordingly, a simple linear regression was done among exposed group (n = 154) to determine how much change in 10-year CHD risk percent would be expected with additional service year at CB manufacturing process. Collinearity was tested with variance inflation factors (VIF); a VIF value of 10 was considered large enough to indicate problematic multicollinearity [25]. For all analyses in this study, the level of significance was considered at 5% (α = 0.05).

Ethics approval and consent to participate
The study was approved by the Research Ethics Committee at the Alexandria Faculty of Medicine, University of Alexandria. Objectives, purpose of the study, expected benefits and types of information and investigations needed, publication were explained to workers. Afterward, an informed written consent was provided by each worker before participation in the study. Confidentiality and security of data was ensured.

Results
Exposed and unexposed workers were comparable in respect to their age (40.79 ± 7.41 compared to 40.05 ± 7.88) and mean duration of service (13.74 ± 6.93 compared to 13.49 ± 6.77). No significant difference was found between exposed and unexposed workers regarding their age, residence, marital status, service duration, history of diabetes mellitus and hypertension as well as family history of CHD. Significantly higher percentage of exposed workers reported smoking (55.2%) compared with unexposed workers (35%) (p < 0.01) ( Table 1).
The mean diastolic blood pressure was significantly higher among exposed workers (81.49 ± 9.75 mmHg) compared with unexposed workers (77.86 ± 9.45 mmHg) (p < 0.01). On the other hand, there was no statistical significant difference between exposed and unexposed workers regarding mean systolic blood pressure ( Table 2).

Discussion
This study revealed that working at CB manufacturing process is significantly associated with increased 10year CHD risk. Ten-year CHD risk% is expected to increase by 0.42 with every additional service-year at CB manufacturing process.
Likewise, Hou et al study (2018) calculated FRS and revealed association between exposure to combustion byproduct (PAHs) and CHD risk, which was explained by the oxidative and inflammatory effects of PAHs on the cardiovascular system [26]. In addition, Cao et al study (2020) investigated the 10-year risk of CVD using China-PAR prediction equation that included age, BMI, waist circumference, smoking status, family history of CVD, systolic blood pressure, total cholesterol, HDL, diabetes mellitus, and urbanization; it revealed association between exposure to PAHs and high 10-year risk of CVD [27]. Other studies also revealed association between exposure to combustion byproducts and CHD, angina pectoris, heart attack or stroke, and myocardial infarction [6][7][8][9][10].
Factors that predict 10-year CHD risk include age, blood pressure, BMI, smoking, and lipid profile. In the present study, the mean diastolic blood pressure was significantly higher among exposed workers; this coincides with the results of El Okda et al study (2014) conducted at carbon black factory [2]. Similarly, other studies examined the effect of exposure to combustion byproducts on blood pressure found that each 1 μg/L increase in urinary PAHs metabolite concentration led to 1.7 mmHg increase in the diastolic blood pressure [28] and revealed association between exposure to sulfur dioxide and increase in diastolic and systolic blood pressure [29].
In the present study, no difference between exposed and unexposed workers regarding hypertension. On the contrary, Bangia et al study (2015) in Mexico [7] and Lee WH et al study (2016) in Korea [30], revealed positive association between exposure to combustion byproducts and hypertension; different findings could be due to larger sample size of those studies (11,218 and 680,202 participants, respectively); different population characteristics; about 77% of the participants in the Mexican study were women [7]. Besides, the Korean study was a longitudinal study where participants were followed up for three years to determine the cumulative effect of exposure [30].
As for lipid profile, according to the current study, working in CB manufacturing process was associated with high levels of total cholesterol, triglyceride and LDL, and with low level of the protective HDL. Similarly, studies revealed significant association between exposure to combustion byproducts and high level of triglycerides, high levels of total cholesterol and LDL, low level of HDL, and a 38%-68% greater risk of dyslipidemia [31,32]. PAHs could bind to (and activate) aryl hydrocarbon receptors which mediate abnormal expression of cytochrome P450 enzyme and promote the development and progression of dyslipidemia, besides, it suppresses hormone induced adipogenesis leading to disordered lipid metabolism [31].
In the present study, significantly higher percentage of exposed workers had high BMI (≥25 kg/m 2 ) compared with unexposed workers. FRS could be calculated using total cholesterol and HDL (Lipid profile-based FRS), or height and weight (BMI-based FRS). In Borhanuddin et al study (2018), BMI-based FRS yielded higher estimation of 10-year CHD risk compared with lipid profile-based FRS [33]. Also, Jones et al study (2015) revealed differences between the two scores Table 3. Framingham risk score; 10-year CHD risk among exposed and unexposed workers (n = 271). and variability that increased with increasing average 10-year risk [34]. Accordingly, it is better that evaluation of an individual's change in CHD risk overtime be assessed using the same risk score (either BMI-based or lipid profile-based) at all screening sessions.

Limitations of the study
This study could not portray the 10-year risk of CHD among women exposed to CB because of their very small number. In addition, it would have been better to exclude workers on triglyceride lowering medications or having chronic diseases that could affect CHD risk. Besides, environmental measurement of levels of exposures at workplace would have been beneficial to study the association between level of exposure (low, moderate, or high) and 10-year CHD risk.

Conclusion
Working at CB manufacturing process could carry an increased risk of CHD. The study recommends that future strategies for reduction of CHD risk focus on active screening of workers by utilizing a simple tool (FRS) to monitor risk over time, motivate workers toward healthy behaviors, and treat hypertension and dyslipidemia for primary prevention of CHD. Further research is required to evaluate work-related factors (factors related to the workplace environment and workers' safety performance) that could predict CHD among workers in CB manufacturing process.

Disclosure statement
No potential conflict of interest was reported by the author(s).

Funding
Authors report that there was no funding source for the work or the preparation of the tools.

Notes on contributors
Ahmed H Hashish, He was graduated from the Faculty of Medicine, University of Alexandria in Egypt, MBBCh. He obtained a master degree in industrial medicine and occupational health. He is an assistant lecturer of occupational health, and a member at the occupational health unit at the Alexandria Faculty of Medicine. Dorria E Meleis, She was graduated from the Faculty of Medicine, University of Alexandria in Egypt. She obtained a master degree in industrial medicine and occupational health, and a doctor degree in industrial medicine and occupational health. She is a professor of occupational health and a member at the occupational health unit at the Alexandria Faculty of Medicine.