Skip to main content
Log in

No evidence of cardiovascular toxicity in workers exposed below 5 ppm carbon disulfide

  • Original Article
  • Published:
International Archives of Occupational and Environmental Health Aims and scope Submit manuscript

Abstract

Purpose

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.

Conclusion

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

HsCRP:

CRP measured by highly sensitive assay

NT-proBNP:

N-terminal pro-brain natriuretic peptide

Lp(a):

Lipoprotein (a)

CV:

Cardiovascular

UACR:

Urinary albumin/creatinine ratio

MI:

Myocardial infarction

AF:

Atrial fibrillation

BMI:

Body mass index

CEI/REI:

Cumulative/recent exposure index

CS2 :

Carbon disulfide

Creat:

Creatinine

TTCA:

Urinary 2-thiothiazolidine-4-carboxylic acid

OEL:

Occupational exposure limit

BP:

Blood pressure

FBG:

Fasting blood glucose

SW:

Shiftwork duration

Pck-y:

Smoking in pack-years

LOD:

Limit Of Detection

ECG:

Electrocardiogram

TLV:

Threshold Limit Value

References

  • Bi Y, Tan X, Wang F et al (1999) Effects of long-term exposure to lower concentration of carbon disulfide on cardiovascular system of workers in a viscose rayon factory. Wei Sheng Yan Jiu 28(5):259–260

    CAS  Google Scholar 

  • Blankenberg S, Zeller T, Saarela O et al (2010) Contribution of 30 biomarkers to 10-year cardiovascular risk estimation in 2 population cohorts: the MONICA, risk, genetics, archiving, and monograph (MORGAM) biomarker project. Circulation 121(22):2388–2397

    Article  Google Scholar 

  • Bøggild H, Knutsson A (1999) Shift work, risk factors and cardiovascular disease. Scand J Work Environ Health 25(2):85–99

    Article  Google Scholar 

  • Boogaard PJ, Caubo ME (1994) Increased albumin excretion in industrial workers due to shift work rather than to prolonged exposure to low concentrations of chlorinated hydrocarbons. Occup Environ Med 51(9):638–641

    Article  CAS  Google Scholar 

  • Braeckman L, Kotseva K, Duprez D et al (2001) Vascular changes in workers exposed to carbon disulfide. Ann Acad Med Singapore 30(5):475–480

    CAS  Google Scholar 

  • Burdelak W, Peplońska B (2013) Night work and health of nurses and midviwes–a review. Med Pr 64(3):397–418

    Google Scholar 

  • Chronic Kidney Disease Prognosis Consortium, Matsushita K, van der Velde M et al (2010) Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet 375(9731):2073–2081

    Article  Google Scholar 

  • Daniels LB, Laughlin GA, Clopton P et al (2008) Minimally elevated cardiac troponin T and elevated N-terminal pro-B-type natriuretic peptide predict mortality in older adults: results from the Rancho Bernardo Study. J Am Coll Cardiol 52(6):450–459

    Article  CAS  Google Scholar 

  • Di Lorenzo L, Basso A, Pesola G et al (2003) Exposure to low doses of CS2 and cardiovascular risk factors. G Ital Med Lav Ergon 25(Suppl 3):112–113

    Google Scholar 

  • Drexler H, Göen T, Angerer J et al (1994) Carbon disulphide. I. External and internal exposure to carbon disulphide of workers in the viscose industry. Int Arch Occup Environ Health 65(6):359–365

    Article  CAS  Google Scholar 

  • Gelbke HP, Göen T, Mäurer M et al (2009) A review of health effects of carbon disulfide in viscose industry and a proposal for an occupational exposure limit. Crit Rev Toxicol 39(Suppl 2):1–126

    Article  CAS  Google Scholar 

  • Gilstrap LG, Wang TJ (2012) Biomarkers and cardiovascular risk assessment for primary prevention: an update. Clin Chem 58(1):72–82

    Article  CAS  Google Scholar 

  • Halperin RO, Sesso HD, Ma J et al (2006) Dyslipidemia and the risk of incident hypertension in men. Hypertension 47(1):45–50

    Article  CAS  Google Scholar 

  • http://www.guideline.gov/content.aspx?id=48340&search=hscrp. 11 Aug 2015

  • http://www.escardio.org/Guidelines-&-Education/Practice-tools/CVD-prevention-toolbox/SCORE-Risk-Charts. 11 Aug 2015

  • http://www.has-sante.fr/portail/upload/docs/application/pdf/2010-09/rapport_marqueurs_cardiaques.pdf. 11 Aug 2015

  • Jourdain P, Lefèvre G, Oddoze C et al (2009) NT-proBNP en pratique, de la biologie à la clinique. Ann Biol Clin 67(3):255–271

    CAS  Google Scholar 

  • Kistorp C, Raymond I, Pedersen F et al (2005) N-terminal pro-brain natriuretic peptide, C-reactive protein, and urinary albumin levels as predictors of mortality and cardiovascular events in older adults. JAMA 293(13):1609–1616

    Article  CAS  Google Scholar 

  • Knutsson A (2003) Health disorders of shift workers. Occup Med (Lond) 53(2):103–108

    Article  Google Scholar 

  • Kones R (2011) Primary prevention of coronary heart disease: integration of new data, evolving views, revised goals, and role of rosuvastatin in management. A comprehensive survey. Drug Des Devel Ther 5:325–380

    Article  Google Scholar 

  • Kotseva K (2001) Occupational exposure to low concentrations of carbon disulfide as a risk factor for hypercholesterolaemia. Int Arch Occup Environ Health 74(1):38–42

    Article  CAS  Google Scholar 

  • Kotseva K, Braeckman L, De Bacquer D et al (2001) Cardiovascular effects in viscose rayon workers exposed to carbon disulfide. Int J Occup Environ Health 7(1):7–13

    Article  CAS  Google Scholar 

  • Lloyd-Jones DM, Liu K, Tian L et al (2006) Narrative review: assessment of C-reactive protein in risk prediction for cardiovascular disease. Ann Intern Med 145(1):35–42

    Article  CAS  Google Scholar 

  • Luo JC, Shih TS, Chang CP et al (2011) Blood oxidative stress in Taiwan workers exposed to carbon disulfide. Am J Ind Med 54(8):637–645

    Article  CAS  Google Scholar 

  • Madjid M, Willerson JT (2011) Inflammatory markers in coronary heart disease. Br Med Bull 100:23–38

    Article  CAS  Google Scholar 

  • Monk TH, Buysse DJ (2013) Exposure to shift work as a risk factor for diabetes. J Biol Rhythms 28(5):356–359

    Article  Google Scholar 

  • Olsen MH, Wachtell K, Tuxen C et al (2004) N-terminal pro-brain natriuretic peptide predicts cardiovascular events in patients with hypertension and left ventricular hypertrophy: a LIFE study. J Hypertens 22(8):1597–1604

    Article  CAS  Google Scholar 

  • Olsen MH, Hansen TW, Christensen MK et al (2007) N-terminal pro-brain natriuretic peptide, but not high sensitivity C-reactive protein, improves cardiovascular risk prediction in the general population. Eur Heart J 28(11):1374–1381

    Article  CAS  Google Scholar 

  • Ridker PM, Danielson E, Fonseca FA et al (2008) Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 359(21):2195–2207. doi:10.1056/NEJMoa0807646

    Article  CAS  Google Scholar 

  • Shimada T (2011) Brief lecture on cardiovascular biomarkers based on the pathophysiology. Rinsho Byori 59(10):958–969

    CAS  Google Scholar 

  • Smith JG, Newton-Cheh C, Almgren P et al (2010) Assessment of conventional cardiovascular risk factors and multiple biomarkers for the prediction of incident heart failure and atrial fibrillation. J Am Coll Cardiol 56(21):1712–1719

    Article  Google Scholar 

  • Sulsky SI, Hooven FH, Burch MT et al (2002) Critical review of the epidemiological literature on the potential cardiovascular effects of occupational carbon disulfide exposure. Int Arch Occup Environ Health 75(6):365–380

    Article  CAS  Google Scholar 

  • Takebayashi T, Nishiwaki Y, Uemura T et al (2004) A six year follow up study of the subclinical effects of carbon disulphide exposure on the cardiovascular system. Occup Environ Med 61(2):127–134

    Article  CAS  Google Scholar 

  • Tan X, Peng X, Wang F et al (2002) Cardiovascular effects of carbon disulfide: meta-analysis of cohort studies. Int J Hyg Environ Health 205(6):473–477

    Article  CAS  Google Scholar 

  • Tan X, Chen G, Peng X et al (2004) Cross-sectional study of cardiovascular effects of carbon disulfide among Chinese workers of a viscose factory. Int J Hyg Environ Health 207(3):217–225

    Article  CAS  Google Scholar 

  • Tsimikas S, Willerson JT, Ridker PM (2006) C-reactive protein and other emerging blood biomarkers to optimize risk stratification of vulnerable patients. J Am Coll Cardiol 47(8 Supp):C19–C31

    Article  CAS  Google Scholar 

  • Vyas MV, Garg AX, Iansavichus AV et al (2012) Shift work and vascular events: systematic review and meta-analysis. DG. BMJ 345:e4800. doi:10.1136/bmj.e4800

    Article  Google Scholar 

  • Wang TJ, Gona P, Larson MG et al (2006) Multiple biomarkers for the prediction of first major cardiovascular events and death. N Engl J Med 355(25):2631–2639

    Article  CAS  Google Scholar 

  • Zannad F, De Backer G, Graham I et al (2012) Risk stratification in cardiovascular disease primary prevention: scoring systems, novel markers, and imaging techniques. Fundam Clin Pharmacol 26(2):163–174

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jérôme Domergue.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Domergue, J., Lison, D. & Haufroid, V. No evidence of cardiovascular toxicity in workers exposed below 5 ppm carbon disulfide. Int Arch Occup Environ Health 89, 835–845 (2016). https://doi.org/10.1007/s00420-016-1122-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00420-016-1122-x

Keywords

Navigation