Registration Dossier

Administrative data

Endpoint:
health surveillance data
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Referenceopen allclose all

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 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 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 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

Reference
Name:
Unnamed
Type:
Constituent
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 Reaction mass of SEX, 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 as a main constituent of Reaction mass of ethanol and sodium O-ethyl dithiocarbonate and sodium hydroxide 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 as a main constituent of Reaction mass of ethanol and sodium O-ethyl dithiocarbonate and sodium hydroxide 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

101(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)

103

32

-

-

 

Japan (JSOH)4

10

31

-

-

yes

Netherlands5

10

30

-

-

yes

Russia

10

30

-

-

 

Switzerland

10

30

20

60

yes

United Kingdom

(HSE)

10

32

-

-

yes

US ACGIH

10

31

-

-

yes

US OSHA6

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 as a main constituent of Reaction mass of ethanol and sodium O-ethyl dithiocarbonate and sodium hydroxide 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 as a main constituent of Reaction mass of ethanol and sodium O-ethyl dithiocarbonate and sodium hydroxide 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 xanthateas a main constituent of Reaction mass of ethanol and sodium O-ethyl dithiocarbonate and sodium hydroxide 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 Reaction mass of SEX and it is therefore important to also consider the health and safety hazards of this substance. Carbon disulphide is readily given off when Reaction mass of SEX comes intocontact with water. Carbon disulphide is very volatile and poses a fire hazard because of its low auto ignition point and high flammability. Carbon disulphide causes acute effects such as severe irritation to the skin and eyes and respiratory system and is toxic by inhalation. Repeated exposure to carbon disulphide may cause long-term effects such as reproductive and CNSeffects. Health effects data indicate that dermal and inhalational exposure to carbon disulphide should be minimised.

 

Situations which are likely to present the greatest risk to workers handling or using Reaction mass of SEX are:

-direct skin contact with Reaction mass of SEX powder or pellets;

-inhalational exposure to Reaction mass of SEX dust;

-direct skin contact with carbon disulphide;

-inhalational exposure to carbon disulphide vapour; and

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