Carbon disulphide

Exposure related observations in humans: other data

Administrative data

Endpoint:

exposure-related observations in humans: other data

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well-documented and acceptable publication which is sufficient for assessement

Data source

Reference

Reference Type:

publication

Title:

Evidence for oxidative stress at elevated plasma thiol levels in chronic exposure to carbon disulfide (CS2) and coronary heart disease

Author:

Teresa Wronska-Nofer, Jerzy-Roch Nofer, Jan Stetkiewicz, Malgorzata Wierzbicka, Halina Bolinska, Manfred Fobker, Helmut Schulte, Gerd Assmann, Arnold von Eckardstein

Year:

2007

Bibliographic source:

Nutrition, Metabolism & Cardiovascular Diseases 17, 546-553

Materials and methods

Type of study / information:

In vivo method regarding to oxidative stress.

Endpoint addressed:

repeated dose toxicity: inhalation

Principles of method if other than guideline:

Plasma oxidative status was examined in subjects occupationally exposed to carbon disulfide (CS2). 55 CS2-exposed workers from the viscose rayon plant and 53 healthy workers recruited from the carpet plant were examined. Exposure to CS2 occured continuously during the entire shift and the employment period varied between 15 and 25 years. concentrations of thiobarbituric reactive substances (TBARS) and total antioxidative capacity (TAC), as well as ferritin and ceruloplasmin were determined. Antioxidative reserve was assessed by the determination of vitamine E, uric acid, superoxide dismutase, catalase, and glutathion peroxidase. In addition, protein and non-protein plasma thiol levels were measured.

Test material

Test material information

Constituent 1

Reference substance name:

Carbon disulphide

EC Number:

200-843-6

EC Name:

Carbon disulphide

Cas Number:

75-15-0

Molecular formula:

CS2

IUPAC Name:

methanedithione

Method

Details on exposure:

TYPE OF EXPOSURE: inhalation (vapour)

TYPE OF EXPOSURE MEASUREMENT: Area air sampling: Mesurements of CS2 concentrations were performed by the staff of the Institute of Occupational Medicine. During normal everyday work average exposure level varied from 20 to 45 mg/m3 and in some areas reached even 65 mg/m3.

EXPOSURE LEVELS: 20 - 45 mg/m3 (max. 65 mg/m3)

EXPOSURE PERIOD: between 15 and 25 years (average 23.4); continuously during the entire shift

Results and discussion

Any other information on results incl. tables

Compared to control, increased levels of plasma thiols associated with plasma proteins were observed. TBARS were significantly increased and total antioxidative reserve (TAC) was significantly decreased in CS2-exposed subjects. In addition decreased activity of glutathione peroxidase, an antioxidative enzyme inhibited by thiol-containing compounds, was noted (table 1). Significant lower HDL-Cholesterol and Apo B concentrations were observed in CS2 -exposed group compared to the control group.

Table 1: Pro- and antioxidative factors (age- and smokers/non-smokers ratio adjusted) in plasma from study subjects

	Control (n = 52)	CS2 (n = 55)	P
Soluble factors
TBARS (µmol/L)	2.1 ± 0.3	3.4 ± 0.7	<0.001
TAC (mmol/L)	1.6 ± 0.2	1.2 ± 0.2	<0.001
Vitamin E (mg/L)	8.3 ± 2.2	7.4 ± 1.9	<0.005
Uric acid (mg/dL)	6.41 ± 1.62	6.21 ± 1.38	n.s.
Ferritin (µg/L)	270.4 ± 161.7	269.0 ± 181.6	n.s.
Ceruloplasmin (mg/dL)	26.2 ± 3.9	25.0 ± 5.4	n.s.
Enzymatic factors
SOD (U/mg Hb)	41.9 ± 8.3	36.9 ± 12.0	n.s.
CAT (kat/g Hb)	112.9 ± 31.6	129.6 ± 50.5	n.s.
GPX (µmol NADPH/g Hb)	27.1 ± 3.1	24.9 ± 4.3	<0.005
Plasma thiols
Homocysteine (µmol/L)	13.4 ± 3.1	14.4 ± 3.5	n.s.
Cysteine (µmol/L)	74.6 ± 16.6	58.2 ± 35.8	n.s.
Cysteinylglycine (µmol/L)	88.4 ± 30.5	73.0 ± 51.2	n.s.
Protein thiols (µmol/L)	114.8 ± 8.0	149.7 ± 45.6	<0.01

n.s. not significant

Table 2: Lipid and apolipoprotein concentrations (age- and smokers/non-smokers ratio adjusted) in study subjects

	Control (n = 52)	CS2 (n = 55)	P
Cholesterol (mg/dL)	216.9 ± 35.1	209.5 ± 36.6	n.s.
Triglycerides (mg/dL)	67.3 < 109.9 < 198.3	71.5 < 117.9 < 194.4	n.s.
HDL-Chol. (mg/dL)	44.7 ± 10.5	40.5 ± 10.2	<0.05
Apo A-I (mg/dL)	130.2 ± 17.4	134.7 ± 20.3	n.s.
Apo B (mg/dL)	100.5 ± 20.9	93.6 ± 19.8	<0.05
Lp(a) (mg/dL)	5.4 < 20.1 < 66.6	9.2 < 22.1 < 55.7	n.s.

n.s. not significant

Applicant's summary and conclusion

Conclusions:

These results demonstrate that CS2 exposed subjects exhibited increased thiols which are associated with increased oxidative stress in plasma.

Executive summary:

To investigate whether plasma thiols act as prooxidants or antioxidants, we compared plasma oxidative status in in subjects occupationally exposed to carbon disulfide (CS2). 55 subjects chronically exposed to CS2 and 52 healthy controls were examined. To assess plasma oxidative status, concentrations of thiobarbituric reactive substances (TBARS) and total antioxidative capacity (TAC), as well as ferritin and ceruloplasmin were determined. Antioxidative reserve was assessed by the determination of vitamine E, uric acid, superoxide dismutase, catalase, and glutathion peroxidase. In addition, protein and non-protein plasma thiol levels were measured. Patients had increased levels of plasma thiols as compared to controls: CS2-exposed subjects presented with increased levels of thiols associated with plasma proteins. TBARS were significantly increased and TAC was significantly decreased in CS2-exposed subjects. In addition decreased activity of glutathione peroxidase, an antioxidative enzyme inhibited by thiol-containing compounds, was noted. These results demonstrate that CS2 exposed subjects exhibited increased thiols which are associated with increased oxidative stress in plasma.