Sodium O-isobutyl dithiocarbonate

Exposure related observations in humans: other data

Administrative data

Endpoint:

exposure-related observations in humans: other data

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Review document that evaluates relevant human data for CS2 and xanthates.. Carbon disulphide is both a reagent in the manufacture, as well as a decomposition product of xanthates. Sodium isobutyl xanthate readily decomposes to carbon disulphide, especially in the presence of moisture/water. Therefore, the health effects of carbon disulphide (CS2) need to be considered in the assessment of sodium isobutyl xanthate.

Data source

Reference

Reference Type:

review article or handbook

Title:

A Review of Health Effects of Carbon Disulfide in Viscose Industry and a Proposal for an Occupational Exposure Limit

Author:

Gelbke HP, Goen T, Mauerer M, Sulsky SI

Year:

2009

Bibliographic source:

Critical Reviews in Toxicology 2009, 1–126

Materials and methods

Type of study / information:

Review of Health Effects of Carbon Disulfide in Viscose Industry and a Proposal for an Occupational Exposure Limit

Endpoint addressed:

repeated dose toxicity: inhalation

toxicity to reproduction / fertility

neurotoxicity

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Under the conditions of use, carbon disulphide is the major decomposition product of sodium isobutyl xanthate and it is therefore important to also consider the health and safety hazards of this substance. Carbon disulphide is readily given off when sodium isobutyl xanthate comes intocontact with water. Carbon disulphide is veryvolatile and poses a fire hazard because of its low auto ignition point and highflammability. Carbon disulphide causes acute effects such as severe irritation to theskin and eyes and respiratory system and is toxic by inhalation. Repeated exposureto carbon disulphide may cause long-term effects such as reproductive and CNS effects. Health effects data indicate that dermal and inhalational exposure tocarbon disulphide should be minimised.

GLP compliance:

not specified

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:

dithioxomethane

Test material form:

aerosol dispenser: not specified

Remarks:

migrated information: aerosol

Details on test material:

Carbon disulphide is both a reagent in the manufacture, as well as a decomposition product of xanthates. Sodium isobutyl xanthate readily decomposes to carbon disulphide, especially in the presence of moisture/water. Therefore, the health effects of carbon disulphide (CS2) need to be considered in the assessment of sodium isobutyl xanthate.
In addition, xanthates decompose on aging to form a number of byproducts, depending on the pH, temperature, etc. Risks associated with xanthate are, therefore, a function of the breakdown of the product or un-reacted raw materials remaining in the product.
- Name of test material (as cited in study report): Carbon disulfide

Method

Ethical approval:

not applicable

Remarks:

Review

Details on study design:

Review of Health Effects of Carbon Disulfide in Viscose Industry and a Proposal for an Occupational Exposure Limit

Exposure assessment:

not specified

Results and discussion

Results:

Increased mortality due to coronary heart disease was observed by several studies of workers exposed to CS2 levels in the range of 10 – 60 pm. A dose response relationship was observed.

Exposure levels of >10 ppm are associated with increased blood cholesterol levels, and increased LDL levels.
No reported increase in blood triglycerides at exposures of 10 ppm.

High exposures show evidence of risk increment of ECG change. Heart rate may be affected by higher exposure concentrations. Insufficient evidence for CS2 having an effect on arterial walls.

Workers exposed to >10 ppm of CS2 experience negative electrophysiological and clinical effects of peripheral nerves. Some studies suggest effects on conduction velocity below 10 ppm.

Workers exposed to > 10 ppm CS2 can experience a variety of psychophysiological and behavioral effects ranging from measured tremors to subjective complaints. There are some reports of psychophysiological impairment among workers exposed to < 10 ppm of CS2, but the overall literature is inconsistent on this topic.

Hearing deficits found in workers exposed to levels >10 ppm CS2 and noise for long times. No effect of hearing found in studies on workers with <10 ppm exposure.

Significant microaneurysms in Japanese exposed compared to unexposed; no microaneurysms in European population;
Exposure-related effect in the high exposure group (>10 ppm).

Data does not allow firm conclusion of blood pressure increase; no exposure-related effect observed in key papers.
No clear effects of CS2 on blood glucose.
No exposure effect seen on blood coagulation factors

Exposures <10 ppm may lead to menstrual cycle disorders.
Inconsistent evidence on the effects 5 ppm of CS2 exposure on pregnancy.
Increased complaints of impotency and reduced sexual desire at levels >10 ppm.
Although no exposure effect was observed on semen quality, male fertility, or on sexual hormones, there is insufficient overall evidence to comment on the association between CS2 exposure at 10 ppm and sperm quality.

No exposure effect on thyroid function at 10 ppm.

Applicant's summary and conclusion

Conclusions:

Studies on cohorts with historical exposure between 10 – 60 ppm document increased coronary heart disease mortality among exposed workers; later studies on workers exposed to lower exposures are absent or methodological inadequate.

An occupational exposure limit of 10 ppm of CS2 is sufficient to protect workers from coronary risk factors.

Studies on retinal angiopathy and various ocular effects among workers exposed to carbon disulfide, support an occupational exposure limit of 10 ppm. However, Japanese workers were found to be at a greater risk of microaneurysms at lower exposures.

Exposure to carbon disulfide above 10 ppm leads to psychophysiological and behavioral disturbances including hearing impairments; slowed nerve conducting velocities have been reported even below 10 ppm.

Among female workers, even exposure to concentrations lower than 10 ppm may lead to menstrual cycle disorders but there is inconsistent evidence on pregnancy outcomes among workers exposed at <5ppm.

Male workers exposed to >10 ppm complained of decreased libido and impotency. Studies on the effect of CS2 exposure of <10 ppm on semen quality, male fertility, or sexual hormones are insufficient to draw any conclusion.

Executive summary:

Studies published after the mid 70’s that could inform occupational exposure limits for carbon disulfide exposure were critically examined to identify methodically sound studies and to assess the robustness of findings. The overall evidence indicated that workers exposed to > 10 ppm of CS2 may have increased coronary heart disease mortality; coronary risk factors, retinal angiopathy, negative ocular effects, psychophysiological and behavioral disturbances, and complaints of impotency and decreased libido. Below 10ppm, Japanese workers had increased microaneurysms, and female workers had more menstrual cycle disorders. Studies which attempted to study health effects of workers exposed to less than 10 ppm faced methodological challenges such as accounting for historical and peak exposures. Current studies are inadequate to draw conclusions about the effect of CS2 at exposure levels <10 ppm.