Styrene gas poisoning: A histopathological study of autopsy cases in a tertiary care center :Venkata Sudhakar Peddireddi, Bhagyalakshmi Atla, Chandra Sekhar Vadde, Satyasri Karri, Venkata Satya Kartheek Botta, Journal of Dr. NTR University of Health Sciences

ORIGINAL ARTICLE
Year : 2022 | Volume : 11 | Issue : 3 | Page : 237--242

Styrene gas poisoning: A histopathological study of autopsy cases in a tertiary care center

Venkata Sudhakar Peddireddi¹, Bhagyalakshmi Atla², Chandra Sekhar Vadde³, Satyasri Karri², Venkata Satya Kartheek Botta²,
¹ Department of Plastic Surgery, Andhra Medical College, Visakhapatnam, Andhra Pradesh, India
² Department of Pathology, Andhra Medical College, Visakhapatnam, Andhra Pradesh, India
³ Department of Forensic Medicine, Andhra Medical College, Visakhapatnam, Andhra Pradesh, India

Correspondence Address:
Dr. Venkata Satya Kartheek Botta
Department of Pathology, Andhra Medical College, Maharanipeta, Visakhapatnam - 530 002, Andhra Pradesh
India

Abstract

Background: Styrene is an organic compound used to make plastics and rubber. Exposure to toxic levels of styrene is a rare phenomenon. Hence, there is a paucity of knowledge of its effect on various organs. The objective of the present study is to study the histopathological features of the organs affected in the deceased persons in a population who have been accidentally exposed to high concentrations of styrene. Methods: The present study is an observational study conducted in the Department of Pathology, Andhra Medical College, Visakhapatnam. Organs from 11 deceased cases were received following autopsy. All the organs were grossly examined and microscopically studied, following staining by Hematoxylin and Eosin stains. Results: In the present study, the lung is the most common organ affected (100%) characterized by acute lung injury. Other organs showing significant histopathological findings were the brain, liver, kidney, and spleen. Brain showing edema and congestion in 90% cases, liver revealed cholestasis, hydropic change, and congestion. In the kidney, cloudy swelling was the most common histopathological finding (70%), and in the spleen, congested sinusoids were seen in 100% of cases. Conclusion: Lungs, brain, liver, kidneys, and spleen showed histopathological changes in the deceased cases following styrene exposure. The lung is the most commonly affected organ leading to acute lung injury.

How to cite this article:
Peddireddi VS, Atla B, Vadde CS, Karri S, Kartheek Botta VS. Styrene gas poisoning: A histopathological study of autopsy cases in a tertiary care center.J NTR Univ Health Sci 2022;11:237-242

How to cite this URL:
Peddireddi VS, Atla B, Vadde CS, Karri S, Kartheek Botta VS. Styrene gas poisoning: A histopathological study of autopsy cases in a tertiary care center. J NTR Univ Health Sci [serial online] 2022 [cited 2023 Mar 22 ];11:237-242
Available from: https://www.jdrntruhs.org/text.asp?2022/11/3/237/365017

Full Text

Introduction

Over the past decades, major industrial accidents have caused mortalities, numerous injuries, significant environmental pollution, and substantial economic loss, such as the Bhopal gas tragedy in 1984, the Bunce field fire in the United Kingdom in 2005, the Deepwater Horizon oil spill in the Gulf of Mexico in 2010, and the Bento Rodriguez dam disaster in Brazil in 2015.[1],[2],[3] Hazardous chemicals can enter into the body through the respiratory tract through inhalation.[4] Once inhaled, chemicals get settled in the respiratory tract, damage the tissue, or diffuse into the blood through the lung–blood interface.[5]

On 7th May 2020, Visakhapatnam in Andhra Pradesh, India, witnessed accidental exposure to high concentrations of styrene. Such exposure to styrene monomer has never happened in the world so far. The present study discusses the morphological changes in the organs that have occurred in the deceased patients exposed to high concentrations of styrene gas.

Materials and Methods

The present study is an observational study conducted in the Department of Pathology, Andhra Medical College (AMC), Visakhapatnam. This study included a total of 11 cases of deceased patients who are exposed to styrene gas. All the 11 cases underwent autopsy in the Department of forensic medicine, AMC, Visakhapatnam. Relevant organs were retrieved and sent to the Department of Pathology, AMC. All the organs had a pungent, noxious smell which caused irritation of the eyes and nose. All the organs received were fixed in 10% formalin. Relevant clinical findings were noted, and gross examination was done, and the organs were subjected to grossing. Tissue bits from the organs were taken from the relevant areas and subjected to tissue processing followed by staining with Hematoxylin and Eosin (H&E). All the sections from the organs were examined under the light microscope, and the histological findings were noted.

Ethical clearance

Ethical approval for this study (Styrene gas poisoning: A histopathological study of autopsy cases in a tertiary care center) was provided by the Institutional Ethical Committee, Andhra Medical College, Visakhapatnam-530002 (AP), Reg No:EC/NEW/INST/2019/397 on 22nd December 2020.

Results

A total of 11 cases were included in the study. Out of 11 cases, 6 were males (54.55%), and 5 were females (45.45%). Out of 11 cases, 2 cases are in pediatric age groups, and both were females. In the present study, age ranged from 6 years to 80 years. The most common age group observed in this study is between 31 and 50 years which constituted 54.55% of the cases [Table 1]. All 11 cases were brought dead to the Emergency Department of King George Hospital, Visakhapatnam, the teaching hospital attached to AMC following exposure to styrene gas.{Table 1}

All 11 cases revealed an unpleasant chemical odor after opening the chest cavity. In two pediatric cases, one was 6 years old, and the other was 10 years old, which revealed bluish discoloration of lips and nails and whitish froth in the nostrils. Lungs: On gross examination, out of 11 cases, 4 cases showed lungs on cut section exhibiting pink frothy fluid. On microscopic examination of lungs, all 11 cases (100%) revealed acute lung injury features comprising congestion, interstitial and intra-alveolar edema, and neutrophilic infiltrates. [Figure 1] One case exhibited impacted small foreign body in the bronchiole with surrounding inflammation. [Figure 2]{Figure 1}{Figure 2}

Brain

In the present study, brain specimens were received from 10 cases. Grossly all the brain specimens received were unremarkable. On microscopic examination of brain specimens, four cases (40%) revealed edema and congestion, three cases (30%) only congestion, and two cases only edema (20%) [Figure 3].{Figure 3}

Liver

In the present study, liver specimens were received from 9 cases. Five cases revealed liver specimens exhibiting yellowish discoloration suggestive of fatty liver. Rests of the liver specimens are grossly unremarkable. On microscopic examination of liver specimens, all the 9 cases (100%) exhibited features of acute liver injury comprising of mild periportal lymphocytic infiltrates [Figure 4], 8 cases (88.88%) exhibited hydropic change [Figure 5], 5 cases (55.55%) revealed cholestasis, 6 cases (55.55%) revealed congestion [Figure 6], and 5 cases (55.55%) microvesicularsteatosis.{Figure 4}{Figure 5}{Figure 6}

Spleen

In the present study, spleen specimens were received from 8 cases. All show grossly unremarkable spleens. Spleen specimens on microscopic examination revealed sinusoidal congestion in all 8 cases (100%).

Kidney

In the present study, kidney specimens were received from 10 cases. All the kidney specimens received were grossly unremarkable. On microscopic examination of kidney specimens, 7 cases (70%) revealed cloudy change, 7 cases (70%) revealed mild to moderate interstitial lymphocytic infiltrates, 2 cases (20%) revealed features of acute kidney injury (AKI) [Figure 7], and 1 case (10%) exhibited features of chronic pyelonephritis. [Table 2].{Figure 7}{Table 2}

Discussion

Styrene is an organic compound with the chemical formula C6H5CH = CH2. Styrene is the precursor to polystyrene and several copolymers. It is widely used to make plastics and rubber. Styrene is absorbed into the body after inhalation, ingestion, or dermal exposure. Increased blood concentrations of styrene or styrene metabolites have been observed in experimental subjects and workers exposed to styrene. Concentrations of styrene in the blood increase rapidly after the onset of exposure and decay over the course of several hours after termination of the exposure.[6]

There are no studies in the English literature related to deaths due to styrene gas exposure in humans. Only studies on animal models have been done in the past. In the present study, mortality was slightly higher in males (54.55%) than in females (45.45%). An increase in mortality was observed in female CD-1, and B6C3F1 female mice exposed to 250 ppm was reported by Morgan et al.[7]

Out of 11 cases, 2 cases are in the pediatric age group in the present study. There are no studies evaluating the effect of styrene exposure on children or immature animals. It is likely that children would have the same health effects as adults.[8]

Studies evaluating inhalation exposure have demonstrated that styrene is a strong irritant. Animal studies on histopathological examinations showed pronounced lung irritation similar to acute lung injury was seen in guinea pigs that died after a few exposures. The irritation included congestion, hemorrhages, edema, exudation, and a general acute inflammatory reaction.[8] Acute lung injury (ALI), also called non-cardiogenic pulmonary edema, is characterized by the abrupt onset of significant hypoxemia and bilateral pulmonary infiltrates in the absence of cardiac failure. Acute lung injury can occur due to inhaled irritants due to high oxygen toxicity, smoke, irritant gases, and chemicals. Morphologically, the lungs exhibit congestion, interstitial and intra-alveolar edema, inflammation, fibrin deposition, and diffuse alveolar damage.[9] In the present study, lung specimens of all the 11 cases revealed features of acute lung injury. One case exhibiting impacted foreign body in the small airways might be due to accidental aspiration of a food particle, an incidental finding.

Exposure to larger amounts of styrene can lead to the onset of “styrene sickness,” which relates to a series of health effects resulting from depression of the central nervous system (CNS). The features of “styrene sickness” include headache, nausea, vomiting, weakness, dizziness, fatigue, and ataxia. In some cases, inhalation of styrene can cause progressive loss of consciousness leading to coma.[9],[10] Styrene, like many other lipid-soluble organic solvents, can be acutely neurotoxic at high concentrations. Styrene-induced neurotoxicity has been reported in workers since the 1970s. Studies over the last 15 years have firmly established the central nervous system as the critical target of toxicity. Both short- and long-term exposures to styrene can result in neurological effects.[11] There are no studies in relation to the effect of Styrene on histological changes in the brain. Cytotoxic cerebral edema is an increase in intracellular fluid secondary to neuronal, glial, or endothelial cell membrane injury, as might be encountered in someone with a generalized hypoxic/ischemic insult or with a metabolic derangement that prevents maintenance of the normal membrane ionic gradient.[12] In patients with severe acute toxic encephalopathy due to exposure to high levels of toxic chemicals, magnetic resonance imaging (MRI) of the brain may show focal areas, most commonly bilateral basal ganglia, or diffuse areas of edema.[13] In the present study, microscopic examination of brain specimens revealed focal edema and congestion in 4 out of 11 cases, 3 cases only congested blood vessels, and in two cases only edema. One case was unremarkable, showing no histological changes.

In animal studies, severe hepatocellular necrosis was observed in mice exposed to 250 ppm for 3 days. Animal studies provide evidence that the liver is a target tissue for Styrene. Exposure to 250 or 500 ppm for 1–4 days resulted in marked to severe hepatocellular necrosis and degeneration in mice. The necrosis was characterized as centrilobular coagulative necrosis and was accompanied by pooling of erythrocytes in dilated sinusoids.[7],[14],[15] In one study, parenchymal hydropic degeneration, steatosis, and congestion were observed in rats exposed to 300 ppm for two weeks.[16] In the present study, microscopic examination of liver specimens revealed different morphological patterns of liver injuries such as mild periportal lymphocytic infiltrates (100%), hydropic change (88.88%), cholestasis and congestion (55.55%), and micro-vesicular steatosis (55.55%).

Based on the results of occupational exposure studies and animal toxicity studies, the kidney does not appear to be a sensitive target of styrene toxicity.[12] No histological alterations were observed in the kidneys following acute exposure of rats to 300 ppm or in mice to 500 ppm in animal studies by Morgan et al. and Vainio et al., respectively.[7],[16] In the present study, cloudy swelling (70%) and focal mild to moderate interstitial lymphocytic infiltrate (70%) were the common histological findings, and acute kidney injury was seen in 20% of cases. One case exhibited features of chronic pyelonephritis in a 73-year-old man. These changes occur due to chronic injuries and cannot be attributed to acute styrene gas exposure. Most of the inhaled styrene is excreted in urine as mandelic acid (MA) and phenyl glyoxylic acid (PGA). However, there are no studies related to MA and PGA causing direct injury to the kidney.[8]

In the present study, all the eight spleen specimens (100%) exhibited congested sinusoids. There are no animal or human studies on Styrene causing splenic toxicity. However, hypoxia can cause increased spleen volume with congested sinusoids.[17]

Conclusion

Exposure to a high concentration of styrene can lead to death. The most common organ affected in styrene poisoning is lung characterized by acute lung injury, followed by spleen exhibiting sinusoidal congestion, brain showing edema and congestion, and liver exhibiting features of acute hepatic injury and cloudy swelling was noted in kidneys.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1	Dash DK. Industrial hazards and safety measures. Pharma tutor, March, 2020. Available from: https://www.pharmatutor.org/articles/industrialhazards-and-safety-measures.
2	International efforts for industrial and chemical accidents prevention, preparedness and response. Inter-agency coordination. OECD & Unicef March, 2020. Available from: https://www.oecd.org/chemicalsafety/chemical-accidents/Brochure-International-efforts-for-industrial-and-chemical-accidents.pdf.
3	Brock WE, Pendergrass JA. Safety & health guide for the chemical industry. Occupational safety and health administration, 2020. Available from: https://www.osha.gov/archive/Publications/osha3091.html.
4	HaSPA (Health and Safety Professionals Alliance). The Core Body of Knowledge for Generalist OHS Professionals. Tullamarine, VIC. Safety Institute of Australia 2012:1-19.
5	Hafeez A, Ahmad S, Al-Taie A, Siqqqui SA, Talwar I, Kamboj A, et al. Industrial hazards and safety management in pharmaceutical industry. Int J Appl Res 2020;6:1-7.
6	Independent Assessment of Styrene. Review of the Styrene Assessment in the National Toxicology Program 12^th Report on Carcinogens. Washington DC: The National Academies Press; 2014. p. 59.
7	Morgan DL, Mahler JF, Dill JA, Price HC Jr, O'Connor RW, Adkins B Jr. Styrene inhalation toxicity studies in mice. II. Sex differences in susceptibility of B6C3F1 mice. Fundam Appl Toxicol 1993;21:317-25.
8	Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for Styrene. Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service; 2010. Available from: https://www.atsdr.cdc.gov/toxprofiles/tp53.pdf.
9	Hussain AN. The lung. In: Kumar V, Abbas AK, Aster JC, editors. Robbins and Cotran Pathologic Basis of Disease. 9^th ed. Canada: Elsevier Saunders; 2015. p. 672-73.
10	International Programme on Chemical Safety (IPCS). Styrene. Environmental Health Criteria 26. Geneva: WHO; 1983. Available from: https://apps.who.int/iris/bitstream/handle/10665/37068/9241540869-eng.pdf.
11	Arnedo-Pena A, Bellido-Blasco J, Villamarin-Vazquez J-L, Aranda-Mares J-L, Font-Cardona N, Gobba F, et al. Acute health effects after accidental exposure to styrene from drinking water in Spain. Environ Health 2003;2:6.
12	Frosch MP, Anthony DC, DeGirolami U. The central nervous system. In: Kumar V, Abbas AK, Aster JC, editors. Robbins and Cotran Pathologic Basis of Disease. 9^th ed. Canada: Elsevier Saunders; 2015. p. 1254.
13	Kim Y, Kim JW. Toxic encephalopathy. Saf Health Work 2012;3:243-56.
14	Morgan DL, Mahler JF, Dill JA, Price HC Jr, O'Connor RW, Adkins B Jr. Styrene inhalation toxicity studies in mice. III. Strain differences in susceptibility. Fundam Appl Toxicol 1993;21:326-33.
15	Morgan DL, Mahler JF, O'Connor RW, Price HC Jr, Adkins B Jr. Styrene inhalation toxicity studies in mice. I. Hepatotoxicity in B6C3F1 mice. Fundam Appl Toxicol 1993;20:325-35.
16	Vainio H, Jarvisalo J, Taskinen E. Adaptive changes caused by intermittent styrene inhalation on xenobiotic biotransformation. Toxicol Appl Pharmacol 1979;49:7-14.
17	Schagatay E, Hubinette A, Lodin-Sundström A, Engan H, Stenfors N. Exercise induced hemoconcentration following spleen contraction in subjects with COPD. COPD Res Pract 2015;1:13.