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Exposure related observations in humans: other data

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Administrative data

Endpoint:
exposure-related observations in humans: other data
Type of information:
other: Review
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Justification for type of information:
Carbon disulphide (CAS number 75–15–0) is both reagents used in the manufacture of S-allyl O-pentyl dithiocarbonate. Therefore, Carbon disulphide (CAS number 75–15–0) need to be considered in the assessment of S-allyl O-pentyl dithiocarbonate.

Data source

Referenceopen allclose all

Reference Type:
review article or handbook
Title:
Schwefelkohlenstoff
Author:
DFG (Deutsche Forschungsgemeinschaft)
Year:
2003
Bibliographic source:
Toxikologisch-arbeitsmedizinische Begründungen fur MAK-Werte, 36. Lieferung, Wiley-VCH, Weinheim.
Reference Type:
review article or handbook
Title:
Schwefelkohlenstoff
Author:
DFG (Deusche Forschungsgemeinschaft)
Year:
1997
Bibliographic source:
Toxikologisch-arbeitsmedizinische Begründungen fur MAK-Werte, 25. Lieferung, Wiley-VCH, Weinheim.
Reference Type:
review article or handbook
Title:
Schwefelkohlenstoff
Author:
DFG (Deutsche Forschungsgemeinschaft)
Year:
1995
Bibliographic source:
Toxikologisch-arbeitsmedizinische Begründungen fur MAK-Werte, Sammelkapitel MAK-Werte und Schwangerschaft, 21. Lieferung, Wiley-VCH, Weinheim.
Reference Type:
review article or handbook
Title:
Schwefelkohlenstoff
Author:
DFG (Deutsche Forschungsgemeinschaft)
Year:
1975
Bibliographic source:
Toxikologisch-arbeitsmedizinische Begründungen fur MAK-Werte, Wiley-VCH, Weinheim.

Materials and methods

Endpoint addressed:
acute toxicity: oral
acute toxicity: inhalation
acute toxicity: dermal
skin irritation / corrosion
eye irritation
skin sensitisation
repeated dose toxicity: inhalation
toxicity to reproduction / fertility
developmental toxicity / teratogenicity
neurotoxicity
Test guideline
Qualifier:
no guideline available
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
Carbon disulphide
EC Number:
200-843-6
EC Name:
Carbon disulphide
Cas Number:
75-15-0
Molecular formula:
CS2
IUPAC Name:
dithioxomethane
Details on test material:
Carbon disulphide (CAS number 75–15–0) is both reagents used in the manufacture of S-allyl O-pentyl dithiocarbonate. Therefore, Carbon disulphide (CAS number 75–15–0) need to be considered in the assessment of S-allyl O-pentyl dithiocarbonate.
- Name of test material (as cited in study report): Carbon disulfide

Method

Ethical approval:
not applicable
Remarks:
Review
Exposure assessment:
not specified

Results and discussion

Results:
No meaningful studies for skin irritation available.

Eye irritation effects among viscose rayon industry workers are ascribed to hydrogen sulfide.

No reports about skin or respiratory tract sensitization available.

Only few reports on acute effects; observed effects after accidents could not definitely been ascribed to CS2.

Evidence for neurotoxic and cardiovascular effects among viscose workers after long-term exposure and exposed at current concentrations of 10-30 mg/m3;

MAK value of 15mg/m3 retained, due to formerly higher exposure concentrations and uncertainties with measurement methods still difficult to derive a scientific sound exposure limit.

Increased mortality in one more recent cohort study; significant increased risk of coronary heart disease in highest exposure group in two studies; Review on cardiovascular effects of CS2 did not find strong or consistent association with mortality on coronary heart diseases.

Increased cholesterol in workers exposed below concentrations of 30mg/m3 and cumulative exposure > 100mg/m3 observed.

Increased triglycerides only in highest exposure group with average concentration of 151.8 ± 76.8 mg/m3.

Elevated blood pressure after long term exposure.

No effects on blood glucose observed.

Ischemic findings among highest exposed.

No effects on blood coagulation at 12mg/m3.

Several parameters of heart rate variability affected exposed at current concentrations of 10-18mg/m3; however other factors might have had an influence.

Reduced arterial wall dispensability observed.

Reduced nerve conduction velocities observed at current median concentrations of 12mg/m3 and max. concentrations of 120mg/m3.

Only workers in highest concentration exposure group (>90mg/m3) showed significant effects in psychomotor tests.

At average concentration level of 18mg/m3 (up to 30mg/m3) higher proportion of "hyperintense spots" by MRI among exposed; no clear association with current exposure and effect.

Auditory impairment observed after exposure >25years, CS2 concentration 10 to 35 mg/m3 and exposure to high noise levels.

At concentrations between 18-30mg/m3 microaneurysms reported among highest exposed.

Studies on color vision deficiency cannot be used due to methodological weaknesses.

Studies on hepatic effects are contradictory.

No relevant endocrine changes observed.

Menstruation disturbances observed at high concentrations but also at concentrations below 10 mg/m3.

Teratogenic effects at concentrations of 15 mg/m3 cannot be excluded with certainty.

Reduced sexual desire at median current concentrations of 12 mg/m3 reported.

Sperm alterations reported when exposed to levels above 30 mg/m3 but results not consistent between studies; newer studies could not confirm effects.

No effects on sex hormones and thyroid function observed.

Applicant's summary and conclusion

Conclusions:
The MAK commission point to the problem with the determination of a NOEC. Whereas generally the actual exposure concentrations at the time of the respective study conduct are well documented, earlier relevant exposures concentrations are not available and had to be estimated. These exposures were often much higher. The usual methods for air exposure measurements used over many years in the past were quite unreliable and often led to an underestimate of the real exposure concentrations.

The MAK commission sees some evidence for neurotoxic and cardiovascular effects among viscose rayon workers which were long-term exposed and currently exposed at concentrations of 10-30 mg/m3. Data are insufficient for lowering the MAK-value of 15mg/m3 and due to the uncertainty with the former exposure levels it is still is difficult to derive a scientific reliable OEL.
Carbon disulphide (CAS number 75–15–0) is both reagents used in the manufacture of S-allyl O-pentyl dithiocarbonate. Therefore, Carbon disulphide (CAS number 75–15–0) need to be considered in the assessment of S-allyl O-pentyl dithiocarbonate.
A teratogenic effect of CS2 at concentrations of 15 mg/m3 cannot be excluded.

No reports about skin or respiratory sensitization are available.
Executive summary:

The German MAK-commission reviewed CS2 in 1975 with updates in 1997 and 2003. In 1995, possible reprotoxic effects were specifically evaluated. In 1975, the German OEL (MAK-value) was set at 10 ppm (DFG, 1975). In 1997, the MAK-value was reduced to 5 ppm (DFG, 1997) on the basis of epidemiological studies of workers showing neurotoxic and cardiotoxic effects after exposures reported to have been at 10 ppm over several decades. In 2003, the preliminary MAK-value of 5 ppm was confirmed after consideration of additional epidemiological investigations (DFG, 2003) The MAK-commission pointed to the problem with the determination of a NOEC: Whereas generally the actual exposure concentrations at the time of the respective study conduct are well documented, earlier relevant exposures concentrations are not available and had to be estimated. These exposures were often much higher. The usual methods for air exposure measurements used over many years in the past were quite unreliable and often led to an underestimate of the real exposure concentrations. The MAK-commission saw some evidence for neurotoxic and cardiovascular effects among viscose rayon workers which were long-term exposed and currently exposed at concentrations of 10-30 mg/m3. Data were seen as insufficient for lowering the MAK-value of 15mg/m3 and due to the uncertainty with the former exposure levels it was assessed as still difficult to derive a scientific reliable OEL. A teratogenic effect of CS2 at concentrations of 15 mg/m3 cannot be excluded according to the MAK-commission (DFG, 2003) No reports about skin or respiratory sensitization were available for the MAK-commission.