title: No evidence of cardiovascular toxicity in workers exposed below 5 ppm carbon disulfide.
abstract: OBJECTIVE
  Carbon disulfide (CS2), used in the viscose process, is well known for having multiple health effects, including on the cardiovascular system, in workers with long-term exposure higher than 10 ppm. The mechanisms of those effects are, however, not precisely defined, and it remains uncertain whether cardiovascular toxicity may occur at exposure levels lower than 10 ppm. Therefore, the purpose of this study is to explore the health impact of low CS2 exposure levels using an array of preclinical biomarkers of cardiovascular risk.
  
  
  METHODS
  Exposure intensity was determined by measuring urinary 2-thiothiazolidine-4-carboxylic acid (TTCA) in 117 workers from two plants using the viscose process, sampled in multiples phases (2003, 2006 and 2013). A cumulative exposure index (CEI) and a recent exposure index (REI) were calculated for each worker, and shiftwork was documented to account for potential confounding. Cardiovascular parameters included blood pressure, total, LDL and HDL cholesterol, triglycerides, C-reactive protein dosed in serum with high sensitivity (HsCRP), N-terminal pro-brain natriuretic peptide, and albuminuria/creatininuria ratio (UACR). Potential biological confounders were fasting blood glucose and serum creatinine. Bivariate and multivariate regression analyses were used to trace relationships between cardiovascular risk biomarkers and other variables, including CEI, REI and shiftwork duration.
  
  
  RESULTS
  Median REI and CEI were 0.05 mg TTCA/g creat and 21.5 mg TTCA/g creat*months, respectively. While expected associations, such as between HsCRP and LDL Cholesterol, were found, significant associations between cardiovascular risk markers and CS2 exposure indexes (CEI or REI) were not detected. Shiftwork duration was positively associated with UACR in workers with elevated fasting blood glucose.
  
  
  CONCLUSIONS
  In practice, when CS2 exposure levels are kept below 5 ppm (TTCA < 2.2 mg/g creat), it does not appear useful to perform a systematic monitoring of total serum cholesterol or its subfractions, or of the new biomarkers of cardiovascular risk (NTproBNP, HsCRP, UACR) investigated in the present study. It appears important to carefully monitor the existence of diabetes that may justify avoiding shiftwork.
authors.affiliation: Centre inter-entreprises et artisanal de Médecine du travail, 45 rue des Vinaigriers, 75010, Paris, France. jerdomergue@free.fr.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Domergue
authors.affiliation: Louvain centre for Toxicology and Applied Pharmacology (LTAP), Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain, Brussels, Belgium.
authors.forename: Dominique
authors.initials: D
authors.lastname: Lison
authors.affiliation: Louvain centre for Toxicology and Applied Pharmacology (LTAP), Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain, Brussels, Belgium.
authors.forename: Vincent
authors.initials: V
authors.lastname: Haufroid
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002097:C-Reactive Protein / Q000032:analysis; D002246:Carbon Disulfide / Q000633:toxicity*; D066126:Cardiotoxicity; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D002617:Chemical Industry; D002784:Cholesterol / Q000097:blood; D003430:Cross-Sectional Studies; D004784:Environmental Monitoring / Q000379:methods; D006801:Humans; D008875:Middle Aged; D009784:Occupational Diseases / Q000139:chemically induced*; D016273:Occupational Exposure / Q000009:adverse effects* / Q000032:analysis; D012044:Regression Analysis; D012307:Risk Factors; D053778:Thiazolidines / Q000652:urine; D013995:Time; D055815:Young Adult
chemical_list: D015415:Biomarkers; D053778:Thiazolidines; C031677:2-thioxo-4-thiazolidinecarboxylic acid; D002097:C-Reactive Protein; D002784:Cholesterol; D002246:Carbon Disulfide
keywords: 2-Thiothiazolidine-4-carboxylic acid (TTCA); Carbon disulfide; Cardiovascular risk; Shiftwork