Sodium O-isobutyl dithiocarbonate

Health surveillance data

Administrative data

Endpoint:

health surveillance data

Type of information:

other: Review of human observational studies

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well-documented observational studies which meets basic scientific principles for Health surveillance.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Carbon disulphide II. Investigations on the uptake of CS2 and the excretion of its metabolite 2-thiothiazolidine-4-carboxylic acid after occupational exposure.

Author:

Drexler H, Goen T, Angerer J

Year:

1995

Bibliographic source:

Int Arch Occup Environ Health, 67(1) 5-10.

Reference 2

Reference Type:

publication

Title:

Environmental and biological monitoring in carbon disulfide exposure assessment.

Author:

Krstev S, Perunucic B, Farkic B et al

Year:

1993

Bibliographic source:

Med Lav, 84(3):473-481.

Reference 3

Reference Type:

publication

Title:

Biological monitoring of workers exposed to carbon disulfide.

Author:

Cox C, Hee SS and Tolos WP

Year:

1998

Bibliographic source:

Am J Ind Med, 33(1):48-54.

Reference 4

Reference Type:

review article or handbook

Title:

TLV-Threshold limit values and biological exposure indices for 1994- 1995

Author:

ACGIH (1994)

Year:

1994

Bibliographic source:

Cincinnati, OH, American Conference of Governmental Industrial Hygienists.

Materials and methods

Study type:

other: Review of human observational studies

Endpoint addressed:

acute toxicity: oral

acute toxicity: inhalation

acute toxicity: dermal

repeated dose toxicity: inhalation

neurotoxicity

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Study conducted according to established standard for Health surveillance methodology.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Sodium O-ethyl dithiocarbonate

EC Number:

205-440-9

EC Name:

Sodium O-ethyl dithiocarbonate

Cas Number:

140-90-9

IUPAC Name:

sodium O-ethyl dithiocarbonate

Constituent 2

Reference substance name:

Sodium ethyl xanthate

IUPAC Name:

Sodium ethyl xanthate

Test material form:

solid: compact

Details on test material:

- Name of test material (as cited in study report):Sodium ethyl xanthate

Method

Type of population:

occupational

Ethical approval:

confirmed, but no further information available

Details on study design:

Adverse health effects have been reported in workers exposed to xanthate products, under current conditions of use, such reports are uncommon and symptomatology is diverse in nature. Because adverse effects from xanthate exposure are generally considered to be associated with exposure to CS2 vapours, the current method of choice for monitoring occupational exposure to xanthates is monitoring CS2 in air.

Results and discussion

Results:

Studies on viscose and rubber workers have demonstrated that urinary 2- thiothiazolidine-4-carboxylic acid (TTCA) levels correlate well with airborne levels of CS2 even at low exposure levels (Krstev et al.,1993; Drexler et al 1995b; Cox et al., 1998). Of interest in a study by Cox et al., (1998) was that low level exposure, below the detection limit (<0.5 ppm CS2) was associated with increasing levels of TTCA during the work shift and that these levels did not return to normal pre-shift levels (0.3 mg/g TTCA in creatinine) before the start of the next shift. This indicates that accumulation of CS2 in body tissues may occur.
Studies in rats and guinea pigs indicate that CS2 is initially accumulated in liver, brain, blood and adrenals.
Significantly increased TTCA excretion has been seen in viscose workers undertaking heavy physical work and in workers with increased potential skin contact (Drexler et al 1995b). A further issue in this regard is the potential contribution to CS2 body burden from dermal exposure to xanthates, the magnitude of which has not been determined.
If bioaccumulation and/or dermal absorption are significant for CS2 and/or sodium ethyl xanthate, then air monitoring may not be an adequate predictor of chronic hazardous exposure to xanthates.
ACGIH has adopted a health-based biological exposure standard (BEI) for CS2, of 5 mg/g TTCA in creatinine (ACGIH, 1994).

Any other information on results incl. tables

An occupational exposure standard for sodium ethyl xanthate or (Sodium isobutyl xanthate the subject of the dossier) has not been assigned by NOHSC or any other country. An ‘in-house’ exposure standard of 1mg/m3 was set by Dow Chemicals in 1976, apparently based on the NOAEL for dogs exposed to the analogue, potassium amyl xanthate.Atmospheric monitoring for sodium ethyl xanthate is not carried out at either the sites of manufacture or end-use.

Monitoring is however carried out for CS2,which is considered to be the major hazard during manufacture, storage and useof xanthates. This would appear justified, particularly for liquid xanthate use, not only with regard to the available toxicological database, but also on the grounds that sodium ethyl xanthate or (Sodium isobutyl xanthate the subject of the dossier) is not particularly volatile and hence inhalation exposure is unlikely to be a major source of exposure to free xanthate.

The NOHSC occupational exposure standard for CS2 is 10 ppm (31 mg/m3) (timeweighted average), with a skin notation (NOHSC 1995). This standard has been adopted from the US ACGIH TLV documentation, which is apparently based on“cardiovascular effects in workers exposed to air concentrations of between 10-40 ppm CS2 and systemic effects observed following skin absorption” (ACGIH1998).

This standard is listed in Appendix 3 (substances under review) of the NOHSCGuidance Note (NOHSC 1995) as requiring review due to ‘neurological andcardiovascular effects’.

Table 6 provides details of known national exposure standards adopted for CS2.

 

  

Table 6 – National exposure standards for carbon disulfide

 

 

Country	Exposure limits				Skin notation
	TWA		STEL
	ppm	mg/m3	ppm	mg/m3
US NIOSH	1	3	10^1(500)^2	30	yes
Hungary	2	5	3	10	yes
Czechoslovakia	3	10	6	20
Denmark	5	15	-	-	yes
Sweden	5	16	8	25	yes
Poland	6	18	10	30
Australia	10	31	-	-	yes
Finland	10	30	20	60	yes
France	10	30	25	75
Germany (DFG)	10^3	32	-	-
Japan (JSOH)^4	10	31	-	-	yes
Netherlands^5	10	30	-	-	yes
Russia	10	30	-	-
Switzerland	10	30	20	60	yes
United Kingdom (HSE)	10	32	-	-	yes
US ACGIH	10	31	-	-	yes
US OSHA^6	20	65	-	-

 

N.B. Source: ACGIH (1998) – Standards current as at Jan 1993 unless otherwise

indicated.

1 = 15-min ceiling concentration

2 = IDLH concentration

3 = Pregnancy Group B (probable risk of damage to developing embryo/foetus)

4 = 1996

5 = Oct 1997

6 = 1995

 

Currently, the highest TWA exposure limit for CS2 (PEL: 20 ppm) is that set by the US OSHA -TWA (OSHA 1995). This exposure limit reflects the exposurelimit that was in effect prior to the issuance of revised limits of 4 ppm (PEL), 12ppm (STEL) and 500 ppm (IDLH) in January 1989, apparently established to“reduce substantially the significant risks of cardiovascular disease, neurologicalimpairment, and adverse reproductive effects associated with exposures to CS2”(OSHA 1989). These revised limits were voided by the US Eleventh Circuit Court of Appeals on 7 July 1992 (ATSDR 1996).

Applicant's summary and conclusion

Conclusions:

Sodium ethyl xanthate or (Sodium isobutyl xanthate the subject of the dossier) exhibits moderate dermal and oral acute toxicity in animal studies and is an eye and skin irritant. Limited animal data exist for chronic exposure to xanthates. Adverse health effects are documented only for acute exposures to xanthates in humans.
The main health hazards from exposure to xanthates are considered to arise from CS2, which is both a decomposition product and metabolite of sodium ethyl xanthate. Carbon disulfide is also a starting reagent in xanthate manufacture. Carbon disulfide exhibits low to moderate acute toxicity in animals and humans and is associated with a number long-term effects, including cardiovascular, neurological and reproductive effects in animals and humans.
An occupational exposure standard for sodium ethyl xanthate or (Sodium isobutyl xanthate the subject of the dossier) has not been assigned by NOHSC or any other country. An ‘in-house’ exposure standard of 1 mg/m3 was set by Dow Chemicals in 1976, apparently based on the NOAEL for dogs exposed to the analogue, potassium amyl xanthate. Atmospheric monitoring for sodium ethyl xanthate is not carried out at either the sites of manufacture or end-use.
The NOHSC occupational exposure standard for CS2 is 10 ppm (31 mg/m3) (time weighted average), with a skin notation (NOHSC 1995). This standard has been adopted from the US ACGIH TLV documentation, which is apparently based on “cardiovascular effects in workers exposed to air concentrations of between 10- 40 ppm CS2 and systemic effects observed following skin absorption” (ACGIH 1998).

Executive summary:

Under the conditions of use, carbon disulphide is the major decomposition product of sodium ethyl xanthate or (Sodium isobutyl xanthate the subject of the dossier) and it is therefore important to also consider the health andsafety hazards of this substance. Carbon disulphide is readily given off whensodiumisobutylxanthate 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 CNSeffects. Health effects data indicate that dermal and inhalational exposure tocarbon disulphide should be minimised.

 

Situations which are likely to present the greatest risk to workers handling or using sodium isobutyl xanthate are:

-direct skin contact with sodium isobutyl xanthate powder or pellets;

-inhalational exposure to sodium isobutyl xanthate dust;

-direct skin contact with carbon disulphide;

-inhalational exposure to carbon disulphide vapour; and

-conditions which are conducive to carbon disulphide formation and itsflammability such as low pH, moisture and heat.

 

Health effects data indicate that dermal exposure to sodiumisobutylxanthate shouldbe avoided and hence the generation of dust should be minimised. Mechanical andphysical damage to the pellets such as sweeping should be avoided to minimise dustgeneration. The particle size of sodium ethyl xanthate powder is in the range of 1 to10 μm (mean 5 μm) and pellet size ranges from 5 to 6 mm. The powder is well withinthe inspirable range (< 185 μm) and the majority is within the respirable range (<7μm). Therefore, there is a greater risk to workers when handling the powder.