UofL experts at the forefront of vinyl chloride health issues research

University researchers have led decades-long studies into the health and environmental effects of chemical production in West Louisville
UofL experts at the forefront of vinyl chloride health issues research

BF Goodrich plant in the area of West Louisville called "Rubbertown."

In the 1970's, Louisville community surgeons noted a cluster of hepatic hemeangiosarcoma (a rare form of liver cancer that is always fatal) among workers at the BF Goodrich rubber plant. They approached the managers of the plant and the UofL Occupational Toxicology group, led by the late Dr. Carlo Tamburro.

A health surveillance program was quickly instituted wherein all plant workers received health exams, blood and urine were obtained, and medical and occupational histories were recorded. It was rapidly determined that exposure to large amounts of vinyl chloride was the cause of the hemeangiosarcoma. Workers were quickly removed from exposure and the Occupational Safety and Health Administration (OSHA) rapidly promulgated regulations for vinyl chloride. This event is considered a seminal event in occupational toxicology.

This surveillance program was originally instituted at all the rubber plants in Louisville ("Rubbertown"/West Louisville). While many of those plants have left Louisville, the surveillance program continued for nearly 50 years, with yearly medical exam records, bloods, urine, death certificates (as deaths occur) and tissue from autopsies, as possible. There are over 15,000 specimens in the biorepository. These samples are still being used in research related to vinyl chloride toxicity.

UofL faculty, including liver specialists Drs. Matthew Cave and Craig McClain, have been working on environmental exposures and liver disease. They identified a form of liver disease, Toxicant Associated Steatohepatitis (TASH), from those samples. Thus, this has been a very important ongoing project between workers, industry and UofL.

Dr. Cave brought the "NIEHS Tamburro Symposium on Environmental Chemicals and Liver Disease" to UofL September 2014, and he also has an National Institute of Environmental Health Sciences (NIEHS) R35 ('RIVER') grant to study environmental liver disease.

This community-identified and joint research/surveillance program with UofL has thrust the university to the forefront nationally in this important emerging area of environmental health. The importance of vinyl chloride is still relevant, as shown from the recent train derailment and vinyl chloride spill in East Palestine, OH. Importantly, grants such as the Hepatobiology & Toxicology COBRE and the Superfund serve as core resources to the country for disasters such as this.

UofL has a strong program in environmental health sciences. It is home to a very long-standing training program in environmental health (NIEHS T32 and T35 grants — Drs. David Hein and J. Christopher States), a Superfund grant (NIEHS P42 grant — Dr. Sanjay Srivastava), an NIEHS Center grant (P30 — Dr. States), a Hepatobiology & Toxicology COBRE Center (NIGMS P20 — Dr. McClain), two NIEHS R35's (Drs. Cave and John Wise), and multiple other research grants from NIH.

Moreover, the Envirome Institute researchers are leaders in the area of environmentally-induced cardiac injury.

Thus UofL is a national resource for expertise in environmentally-induced organ injury and disease, including vinyl chloride toxicity.  Some leading UofL environmental exposure investigators include: Drs. Cave, McClain, Srivastava, Wise, Hein, States, and Russell Prough, Banrida Wahlang, Aruni Bhatnagar, and others.

Selected recent publications on vinyl chloride from UofL include:

  • Wahlang B, Beier JI, Clair HB, Bellis-Jones HJ, Falkner KC, McClain CJ, Cave MC. Toxicant-associated steatohepatitis. Toxicol Pathol., 2013 Feb;41(2):343-60. PMID: 23262638; PMCID: PMC5114851; doi: 10.1177/0192623312468517. Epub 2012 Dec 21.
  • Zelko IN, Taylor BS, Das TP, Watson WH, Sithu ID, Wahlang B, Malovichko, MV, Cave MC, Srivastava S. Effect of vinyl chloride exposure on cardiometabolic toxicity. Environ Toxicol. 2022 Feb;37(2):245-255. PMID: 34717031; PMCID: PMC8724461; doi: 10.1002/tox.23394. Epub
  • Wahlang B, Jin J, Beier JI, Hardesty JE, Daly EF, Schnegelberger RD, Falkner KC, Prough RA, Kirpich IA, Cave MC. Mechanisms of Environmental Contributions to Fatty Liver Disease. Curr Environ Health Rep. 2019 Sep;6(3):80-94. PMID: 31134516; PMCID: PMC6698418; doi: 10.1007/s40572-019-00232-w.
  • Cave M, Falkner KC, Ray M, Joshi-Barve S, Brock G, Khan R, Bon Homme M, McClain CJ. Toxicant-associated steatohepatitis in vinyl chloride workers. Hepatology. 2010 Feb;51(2):474-81. PMID: 19902480; PMCID: PMC4019991; DOI: 10.1002/hep.23321
  • Wahlang B, Hardesty JE, Head KZ, Jin J, Falkner KC, Prough RA, Cave MC, Beier JI. Hepatic Injury Caused by the Environmental Toxicant Vinyl Chloride is Sex-Dependent in Mice. Toxicol Sci. 2020 Mar 1;174(1):79-91. PMID: 31774537; PMCID: PMC7043220; DOI: 10.1093/toxsci/kfz236
  • Guardiola JJ, Hardesty JE, Beier JI, Prough RA, McClain CJ, Cave MC.  Plasma Metabolomics Analysis of Polyvinyl Chloride Workers Identifies Altered Processes and Candidate Biomarkers for Hepatic Hemangiosarcoma and Its Development.  Int J Mol Sci. 2021 May 11;22(10):5093.PMID: 34065028; PMCID: PMC8150673; DOI: 10.3390/ijms22105093
  • Anders LC, Yeo H, Baelin BR, Lang AL, Bushau AM, Douglas AN, Cave M, Arteel GE, McClain CJ, Beier JI.  Role of dietary fatty acids in liver injury caused by vinyl chloride metabolites in mice. Toxicol Appl Pharmacol. 2016 Nov 15;311:34-41. PMID: 27693805; PMCID: PMC5079761; DOI: 10.1016/j.taap.2016.09.026. Epub 2016 Sep 28.
  • Guardiola JJ, Beier JI, Falkner KC, Wheeler B, McClain CJ, Cave M. Occupational exposures at a polyvinyl chloride production facility are associated with significant changes to the plasma metabolome. Toxicol Appl Pharmacol. 2016 Dec 15;313:47-56. PMID: 27765658; PMCID: ; PMC5712227; doi: 10.1016/j.taap.2016.10.001. Epub 2016 Oct 17.