|Year : 2022 | Volume
| Issue : 3 | Page : 189-192
Chronic low-dose exposure to highly toxic gas phosgene and its effect on peak expiratory flow rate
Rajnarayan R Tiwari1, Sampathraju Raghavan2
1 Department of Environmental Epidemiology, ICMR-National Institute for Research in Environmental Health, Bhopal, Madhya Pradesh, India
2 Department of Industrial Hygiene, CMR- Regional Occupational Health Centre (Southern), Bengaluru, Karnataka, India
|Date of Submission||18-Oct-2020|
|Date of Decision||10-Feb-2022|
|Date of Acceptance||24-Mar-2022|
|Date of Web Publication||26-Sep-2022|
Dr. Rajnarayan R Tiwari
ICMR-National Institute for Research in Environmental Health, Bhopal Bypass Road, Bhauri, Bhopal, Madhya Pradesh - 462 030
Source of Support: None, Conflict of Interest: None
Introduction: Phosgene is a highly toxic gas causing irritation of the airways and eyes though at high dose exposure. The effect on airways can be assessed by peak expiratory flow rate (PEFR) which is a cheaper, simple, and easy to perform test under field conditions and routine monitoring. Thus, this study is undertaken to understand the effect of chronic low-dose phosgene exposure on PEFR and the associated factors. Methods: This study included 287 workers of phosgene production and captive units. After recording the demographic, occupational, and clinical history on a questionnaire, every participant was subjected to clinical examination, chest radiography, and measurement of PEFR using Spirovit SP-10. Results: The mean age and mean duration of the job of participants was 42.8 ± 10.4 years and 18.9 ± 9.6 years, respectively. The PEFR was significantly reduced with increasing age, increasing duration in the job, and those having direct exposure. Conclusion: PEFR is affected by chronic low-dose exposure to phosgene.
Keywords: India, PEFR, phosgene, toxic gas
|How to cite this article:|
Tiwari RR, Raghavan S. Chronic low-dose exposure to highly toxic gas phosgene and its effect on peak expiratory flow rate. Indian J Occup Environ Med 2022;26:189-92
|How to cite this URL:|
Tiwari RR, Raghavan S. Chronic low-dose exposure to highly toxic gas phosgene and its effect on peak expiratory flow rate. Indian J Occup Environ Med [serial online] 2022 [cited 2022 Dec 7];26:189-92. Available from: https://www.ijoem.com/text.asp?2022/26/3/189/357029
| Introduction|| |
Phosgene is a highly toxic, colorless gas at room temperature and standard pressure. Phosgene first gained a reputation worldwide during World War I, when it was used in chemical warfare. It was the principal-agent used, accounting for approximately 80% of the 100,000 gas-induced casualties.,, Phosgene is primarily used as a building block in various pharmaceutical and organic industries. Most of the commercially produced phosgene is used captively at the production sites in the manufacture of other chemicals.
The manufacturing process of phosgene includes ignition of petroleum coke and passing of carbon monoxide in a phosgene reactor at the required flow rate. This is followed by transferring and heating of anhydrous chlorine gas stored at −32°C in a cylinder feeding into a phosgene reactor. The carbon monoxide reacts with chlorine gas to produce 100% phosgene.
The manufacture of isocyanates consumes about 85% of the world's phosgene production. The primary use of phosgene is in the production of toluene diisocyanate, a precursor of the polyurethane resins used to make foams, elastomers, and coatings. Phosgene is also used in the manufacture of herbicides, pesticides, dyes, and pharmaceuticals. In addition to its industrial production, suspected sources of atmospheric phosgene are fugitive emissions, thermal decomposition of chlorinated hydrocarbons, and photo-oxidation of chloroethylenes. Phosgene exposure can occur in fires involving certain chlorinated organic compounds found in many household solvents, paint removers, and dry-cleaning fluids or wool, polyvinyl chloride, and other plastics. Phosgene at a concentration of 1 ppm in the air causes little or no immediate irritation, but after a latent period of some hours, it may cause severe pulmonary edema and at concentrations of 4–10 ppm in air, it causes irritation of the respiratory tract and eyes.
Being a highly toxic gas, which may be misused, all efforts are taken not only for its security and safety. Even international agencies such as Organization for Chemical Weapons (OCW) regularly inspect installations that handle or produce phosgene. Thus, an accidental acute exposure scenario is extremely rare. This opens the possibility of chronic low-dose exposure and its related effects. Also, as phosgene is only slightly water-soluble, significant irritation of the upper respiratory tract and eyes may not occur, leading to prolonged low-dose exposure.
The route of exposure is inhalation and thus the respiratory system is the first system to be affected. Peak expiratory flow rate (PEFR) measurement has been promoted as a useful tool for assessing airway obstruction. It is not only cheap but has high reproducibility and user compliance rates, making it a useful tool for ambulatory monitoring of airways disease such as asthma., The toxic effects of gases like phosgene also result in airway problems. However, the studies on the effect of chronic low-dose exposure of phosgene on spirometry particularly PEFR is not reported in the literature. Thus, the present study was carried out among phosgene manufacturing and captive plants to understand the effect of low-dose chronic exposure to the toxic gas on PEFR and the factors associated with it.
| Material and Methods|| |
The present study was designed as a cross-sectional study. Two hundred and eighty-seven male workers of two phosgene manufacturing and captive units were included in the current study. All the workers of the selected units were included in the study. Institutional Ethics Committee of National Institute of Occupational Health, Ahmedabad has approved the study, and informed written consent was taken from each participant before initiating the data collection. On a predesigned pretested questionnaire, questions regarding age, sex, educational status, socio-economic status, nature of the job, duration of employment, and respiratory symptoms were recorded by one-to-one interview method. Each participant was then subjected to clinical examination, chest radiography, and PEFR measurement. The PEFR of the subject was measured using Spirovit SP-10 (Maker Schiller AG, Switzerland). After calibrating the spirometer according to the procedure given in the catalog, three readings of PEFR of each subject were taken. The reading showing the highest flow were recorded and used for further analysis. The predicted PEFR for each individual was calculated by using the Dikshit regression equation and those having less than 80% of the predicted value were considered as having reduced PEFR.
The operational definition of respiratory morbidity was the presence of abnormal findings (increased bronchovascular markings) on chest radiography and/or the presence of respiratory symptoms. The nature of exposure was dichotomized based on their designation. Those working as frontline workers such as helpers, operators, fitters, and mechanics were considered as directly exposed while those working as an executive, manager, supervisor, peon, and cook were considered as indirectly exposed. Statistical analysis was carried out using the statistical software package SPSS 25.0 (International Business Machines Corporation, New York). The distribution of study variables was shown as frequency and percentages. The comparison of the mean value of PEFR according to study variables was done using one-way analysis of variance (ANOVA) and t-test. The correlation between PEFR and study variables was shown through the calculation of Pearson's correlation coefficient. The adjusted analysis of mean PEFR was done using two-way ANOVA.
| Results|| |
The present study included 287 male workers working in two phosgene production and captive plants in the Western state of Gujarat in India. The mean age of the participants was 42.8 ± 10.4 years with a majority (59.9%) of the workers above 40 years. The median monthly income earned by participants was Rs. 8000. The personal habits of participants revealed that 48 (16.7%), 52 (18.1%), and 23 (8%) were smokers, tobacco chewers, and alcohol drinkers, respectively. The mean duration in the job was 18.9 ± 9.6 years with 123 (42.9%) workers working for more than 20 years.
[Table 1] describes the mean observed PEFR according to the study variables. The overall PEFR was 7.16 ± 1.59 L/s. It can be observed that the PEFR was significantly reduced with increasing age (F = 6.88; P = 0.000), increasing duration in the job (F = 7.41; P = 0.001), and those having direct exposure (F = 11.95; P = 0.001). Similarly, those having respiratory morbidity had lower mean PEFR as compared to those free from any respiratory morbidity and the difference was marginally non-significant. When observed PEFR was compared with predicted PEFR, only 19 (6.6%) participants had reduced PEFR.
[Table 2] shows the correlation between the PEFR and study variables. A strong negative correlation of PEFR with age, duration in the job, and nature of work were observed. Similarly, a strong positive correlation was found between the height and weight of the participants. However, no correlation with body mass index (BMI) and a marginally non-significant negative correlation were observed with respiratory morbidity.
[Table 3] shows the mean observed PEFR according to the presence or absence of respiratory morbidity after adjusting for the study factors, i.e., age, sex, duration of exposure, and smoking habits. It can be observed that the mean observed PEFR was lower in those having respiratory morbidity as compared to those free from any respiratory morbidity and the difference was found to be statistically significant.
|Table 3: PEFR (Mean±SD) values in L/min according to respiratory morbid conditions after adjusting for other study variables|
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| Discussion|| |
The present study was carried out to assess the effect of chronic low exposure to highly toxic gas phosgene on the PEFR of workers. The overall mean PEFR was found to be 7.16 ± 1.59 L/s. With the increasing age, a statistically significant declining trend in mean PEFR was observed. Further, when a correlation between PEFR and age was done, a significant negative correlation was observed. Similarly, those on the job for a greater number of years and those working as frontline workers at the production sites were found to have significantly lower PEFR.
The effect of increasing age on PEFR can be partly attributed to stiffening of the thoracic cage from calcification of the rib cage and age-related kyphosis from osteoporosis reducing the ability of the thoracic cage to expand during inspiration and placing the diaphragm at a mechanical disadvantage to generate effective contraction. Additionally, the declining muscle contractile strength with aging will also affect ventilatory functions including PEFR. This may be the reason for several rehabilitation activities involving exercises for improving muscle strength.
The significant decline in the PEFR with increasing duration of employment can be attributed to cumulative exposure to toxic gas phosgene causing irritation of the upper respiratory mucosa. Initially, the response may be in the form of transient bronchial hyper-responsiveness and bronchospasm. However, the continued exposure may result in other mechanisms also such as sensitization and mucus plug formation causing continued obstruction to exhaled air. This may reduce the PEFR.
The workers working as helpers, fitters, mechanics, and operators are directly exposed at production plants and thus had lower values of PEFR as compared to those working in the office and laboratory. Though the measurement of the phosgene gas and its constituent gases such as chlorine and carbon monoxide were not conducted, the surrogate measures such as duration of employment and nature of job suggest cumulative exposure.
On univariate analysis, those having respiratory morbidity were found to have lower PEFR values as compared to those free from it and the difference was marginally non-significant. However, after adjusting for the study variables, those having respiratory morbidity had significantly lower PEFR. Most of those having respiratory morbidity had fibrosis in the lung parenchyma, which may be attributed to tuberculosis. Though changes in lung parenchymal fibrosis results in the reduction in forced vital capacity (FVC), the decline in PEFR suggests some role of gaseous exposure on respiratory airways.
The smokers were found to have lower PEFR as compared to non-smokers and the difference was statistically non-significant. This may be attributed to a low sample size of smokers in the study, which could be underreporting of smoking habits as smoking is strictly prohibited at these installations. When adjusted, the smokers having respiratory morbidity had significantly lower PEFR than non-smokers, which suggests the dual role of respiratory abnormality and smoking in reducing the PEFR. As the literature suggests, the effect of smoking may be exerted through nicotine and the smoke of tobacco causing irritation of the upper airways.
The generalization of the study findings should be done with precautions as the study has certain limitations. Firstly, the study has analyzed a single PEFR measurement. Ideally, a serial PEFR is a much better indicator of the effect on the bronchial tree. Secondly, the measurement of toxic gas at the workplace was not done which limits the establishment of dose-response analysis. However, surrogate measures like duration of employment and process of work were used to crudely understand the extent of exposure.
Thus, to conclude, the study revealed that chronic low-dose exposure to phosgene may result in the reduction of the PEFR. However, the low prevalence of those having reduced PEFR suggests that the measures taken for the safety and security of the installations handling phosgene gas were appropriate. These measures included a safety water curtain around silos storing phosgene, continuous online monitoring for any gas leakage, periodic safety drills, etc. This has also averted any accidental acute exposure. Still, it is recommended that these workers should be subjected to periodic health monitoring in addition to regular environmental monitoring.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]