IPCS INCHEM Home

THIODIGLYCOL

1. NAME
   1.1 Substance
   1.2 Group
   1.3 Synonyms
   1.4 Identification numbers
      1.4.1 CAS number
      1.4.2 Other numbers
   1.5 Main brand names, main trade names
   1.6 Main manufacturers, main importers
2. SUMMARY
   2.1 Main risks and target organs
   2.2 Summary of clinical effects
   2.3 Diagnosis
   2.4 First-aid measures and management principles
3. PHYSICO-CHEMICAL PROPERTIES
   3.1 Origin of the substance
   3.2 Chemical structure
   3.3 Physical properties
      3.3.1 Colour
      3.3.2 State/Form
      3.3.3 Description
   3.4 Hazardous characteristics
4. USES
   4.1 Uses
      4.1.1 Uses
      4.1.2 Description
   4.2 High risk circumstance of poisoning
   4.3 Occupationally exposed populations
5. ROUTES OF EXPOSURE
   5.1 Oral
   5.2 Inhalation
   5.3 Dermal
   5.4 Eye
   5.5 Parenteral
   5.6 Others
6. KINETICS
   6.1 Absorption by route of exposure
   6.2 Distribution by route of exposure
   6.3 Biological half-life by route of exposure
   6.4 Metabolism
   6.5 Elimination and excretion
7. TOXICOLOGY
   7.1 Mode of action
   7.2 Toxicity
      7.2.1 Human data
         7.2.1.1 Adults
         7.2.1.2 Children
      7.2.2 Relevant animal data
      7.2.3 Relevant in vitro data
      7.2.4 Workplace standards
      7.2.5 Acceptable daily intake (ADI)
   7.3 Carcinogenicity
   7.4 Teratogenicity
   7.5 Mutagenicity
   7.6 Interactions
9. CLINICAL EFFECTS
   9.1 Acute poisoning
      9.1.1 Ingestion
      9.1.2 Inhalation
      9.1.3 Skin exposure
      9.1.4 Eye contact
      9.1.5 Parenteral exposure
      9.1.6 Other
   9.2 Chronic poisoning
      9.2.1 Ingestion
      9.2.2 Inhalation
      9.2.3 Skin exposure
      9.2.4 Eye contact
      9.2.5 Parenteral exposure
      9.2.6 Other
   9.3 Course, prognosis, cause of death
   9.4 Systematic description of clinical effects
      9.4.1 Cardiovascular
      9.4.2 Respiratory
      9.4.3 Neurological
         9.4.3.1 Central nervous system
         9.4.3.2 Peripheral nervous system
         9.4.3.3 Autonomic nervous system
         9.4.3.4 Skeletal and smooth muscle
      9.4.4 Gastrointestinal
      9.4.5 Hepatic
      9.4.6 Urinary
         9.4.6.1 Renal
         9.4.6.2 Other
      9.4.7 Endocrine and reproductive systems
      9.4.8 Dermatological
      9.4.9 Eye, ear, nose, throat: local effects
      9.4.10 Haematological
      9.4.11 Immunological
      9.4.12 Metabolic
         9.4.12.1 Acid-base disturbances
         9.4.12.2 Fluid and electrolyte disturbances
         9.4.12.3 Others
      9.4.13 Allergic reactions
      9.4.14 Other clinical effects
      9.4.15 Special risk
   9.5 Other
   9.6 Summary
10. MANAGEMENT
   10.1 General principles
   10.2 Life supportive procedures and symptomatic/specific treatment
   10.3 Decontamination
   10.4 Enhanced elimination
   10.5 Antidote treatment
      10.5.1 Adults
      10.5.2 Children
   10.6 Management discussion
11. ILLUSTRATIVE CASES
   11.1 Case reports from the literature
12. ADDITIONAL INFORMATION
   12.1 Specific preventive measures
   12.2 Other
13. REFERENCES
14. AUTHOR(S), REVIEWER (S)

International Programme on Chemical Safety

Poisons Information Monograph 980

Chemical

1. NAME

1.1 Substance

Thiodiglycol

1.2 Group

Organic sulphur compound (a thio ether and an aliphatic diol)

1.3 Synonyms

Glyecine A; Kromfax solvent; Thiodiethylene glycol; beta-Thiodiglycol (RTECS).

1.4 Identification numbers

1.4.1 CAS number

CAS number: 111-48-8

1.4.2 Other numbers

RTECS number: KM2975000 (RTECS).

1.5 Main brand names, main trade names

No data available.

1.6 Main manufacturers, main importers

Aldrich Chemical Co., Sigma Chemical Co.

2. SUMMARY

2.1 Main risks and target organs

Based on the structural similarity to ethylene glycol thiodiglycol may produce depression of the central nervous system, metabolic acidosis and renal failure in severe intoxication.

2.2 Summary of clinical effects

Thiodiglycol has been reported to be relatively non-toxic in animals. However studies carried out in 1941 on rats and guinea pigs showed irritation in the digestive tract and some effects on the kidney and bile after exposure to large amounts of thiodiglycol.

2.3 Diagnosis

Diagnosis is based on history of exposure and clinical features.

The patient can appear intoxicated but without the odor of ethanol.

2.4 First-aid measures and management principles

Treatment with ethanol will compete with thiodiglycol for the enzyme alcohol dehydrogenase and can slow down the formation of acidic metabolites. The suggested dosing regimen for intravenous ethanol consists of a loading dose of 10 cc/kg of a 10% ethanol solution followed by a continous infusion of 1.5 cc/kg/h. This may be administered orally or intravenously.

3. PHYSICO-CHEMICAL PROPERTIES

3.1 Origin of the substance

Synthetic.

3.2 Chemical structure

Structural formula

HO-CH2-CH2-S-CH2-CH2-OH

Molecular formula

C4H10O2S

Molecular weight

122.19

Structural names

2,2'-thiodiethanol; Bis(beta-hydroxyethyl)sulfide; Bis(2-hydroxyethyl)sulfide; beta, beta'-Dihydroxydiethyl sulfide; beta, beta'-Dihydroxyethyl sulfide; beta-Hydroxyethyl sulfide; Sulfide, bis(2-hydroxyethyl) (RTECS); 2,2'-thiobis ethanol (Sigma); 2-hydroxyethyl sulfide (Aldrich); Bis(hydroxyethyl)sulfide (Budavari 1996).

3.3 Physical properties

3.3.1 Colour

Colourless (Lewis, 1996).

3.3.2 State/Form

Liquid-viscous fluid.

3.3.3 Description

Miscible in water and alcohol, slightly soluble in ether, chloroform (Budavari 1996)

Boiling point: 168C (Budavari 1996)

Melting point: -16C (Budavari 1996)

Flash point: 160C (Budavari 1996)

3.4 Hazardous characteristics

Combustible when exposed to heat or flame. Reacts violently with acetone and sodium peroxide. When heated to decomposition it emits highly toxic fumes of SOx (Lewis, 1996).

4. USES

4.1 Uses

4.1.1 Uses

4.1.2 Description

Thiodiglycol is used as a precursor for sulphur mustard (Lee et al., 1996). It is also an important primary metabolite of sulphur mustard formed by simple hydrolysis (Davison et al., 1961; Roberts & Warwick, 1963).

4.2 High risk circumstance of poisoning

Chemical workers manufacturing sulphur mustard gasses.

4.3 Occupationally exposed populations

People employed in factories manufacturing sulphur mustard.

5. ROUTES OF EXPOSURE

5.1 Oral

No human data available. In rat studies absorbed by this route.

5.2 Inhalation

No data available.

5.3 Dermal

No human data available. In rat studies absorbed by this route.

5.4 Eye

No data available.

5.5 Parenteral

No data available.

5.6 Others

No data available.

6. KINETICS

6.1 Absorption by route of exposure

No data available.

6.2 Distribution by route of exposure

No data available.

6.3 Biological half-life by route of exposure

The apparent half-life of thiodiglycol in the urine of rats after cutaneous application of sulphur mustard is 2.4 days (Black et al., 1992).

6.4 Metabolism

Thiodiglycol is oxidized to four metabolites. In three of the four metabolites sulphur undergoes oxidation and in two of them acetic acid is formed. No information of toxic effects of the metabolites is recorded (Black et al., 1993). In rodents thiodiglycol can conjugate with glucuronic acid and sulphate or it can be converted to thiodiglycolic acid which can conjugate with glycine and glucuronic acid (Somani & Babu, 1989).

6.5 Elimination and excretion

90% of an intraperitoneal dose of thiodiglycol in rats was excreted in the urine within 24 h and by 8 days virtually all of the dose had been excreted. There was no significant excretion in the faeces. The major metabolite was thiodiglycol sulphoxide, minor metabolites were thiodiglycol sulphone, S-(2-hydroxyethylsulphinyl)acetic acid and

S-(2-hydroxyethylthio)acetic acid. Only around 0.5 to 1% of thiodiglycol was excreted unchanged (Black et al., 1993). Background levels of thiodiglycol in human urine are normally <1 ng/mL (Black & Read, 1995).Others have reported background levels of thiodiglycol to be from 1 to 55 ng/mL (Wils et al., 1985, Wils et al., 1988). The source of these background levels is unknown (Black & Read, 1995).

7. TOXICOLOGY

7.1 Mode of action

No data available.

7.2 Toxicity

7.2.1 Human data

7.2.1.1 Adults

No data available.

7.2.1.2 Children

No data available.

7.2.2 Relevant animal data

LD50 (lethal dose that kills 50% of animals exposed) values for Thiodiglycol:

LD50, Rabbit, adminstration onto the skin: 20 mL/kg (Union carbide data sheet 1971).

LD50, Mouse, subcutaneous: 4 to 5 mL/kg (Anslow et al., 1948).

LD50, Rat, subcutaneous: 4 mL/kg (Anslow et al., 1948).

LD50, Rat,oral: 6.61 g/kg (Smyth et al., 1941).

LD50, Guinea pig, oral: 3.96 g/kg (Smyth et al., 1941).

7.2.3 Relevant in vitro data

No data available.

7.2.4 Workplace standards

No data available.

7.2.5 Acceptable daily intake (ADI)

No data available.

7.3 Carcinogenicity

No data available.

7.4 Teratogenicity

No data available.

7.5 Mutagenicity

No data available.

7.6 Interactions

No data available.

8. TOXICOLOGICAL ANALYSES AND
BIOMEDICAL INVESTIGATIONS

9. CLINICAL EFFECTS

9.1 Acute poisoning

9.1.1 Ingestion

No data available.

9.1.2 Inhalation

No data available.

9.1.3 Skin exposure

Administration of 500 mg thiodiglycol onto rabbit skin showed a mild irritation (Union carbide data sheet 1971).

9.1.4 Eye contact

0.5 mL of undiluted thiodiglycol administered into the rabbit eye, induced a moderate severe reaction (Carpenter & Smyth, 1946). No further information about the clinical effects of thiodiglycol is available.

9.1.5 Parenteral exposure

No data available.

9.1.6 Other

No data available.

9.2 Chronic poisoning

9.2.1 Ingestion

No data available.

9.2.2 Inhalation

No data available.

9.2.3 Skin exposure

No data available.

9.2.4 Eye contact

No data available.

9.2.5 Parenteral exposure

No data available.

9.2.6 Other

No data available.

9.3 Course, prognosis, cause of death

No data available.

9.4 Systematic description of clinical effects

9.4.1 Cardiovascular

No data available.

9.4.2 Respiratory

No data available.

9.4.3 Neurological

9.4.3.1 Central nervous system

No data is available on thiodiglycol and its effect on the CNS. Clinical effects could be similar to the clinical effects of ethylene glycol (1,2-ethanediol) (HO-CH2-CH2-OH) (Budavari 1996), based on a similar chemical structure of the two compounds. Ethylene glycol acts as a central nervous system depressant, with the patient appearing acutely intoxicated but without the odor of ethanol (Davis et al., 1997).

9.4.3.2 Peripheral nervous system

No data available.

9.4.3.3 Autonomic nervous system

No data available.

9.4.3.4 Skeletal and smooth muscle

No data available.

9.4.4 Gastrointestinal

No data available.

9.4.5 Hepatic

No data available.

9.4.6 Urinary

9.4.6.1 Renal

No data available on thiodiglycol, however acidic metabolites of ethylene glycol can cause acute tubular necrosis, primarily of the proximal tubules (Davis et al., 1997).

9.4.6.2 Other

No data available.

9.4.7 Endocrine and reproductive systems

No data available.

9.4.8 Dermatological

No data available.

9.4.9 Eye, ear, nose, throat: local effects

No data available.

9.4.10 Haematological

No data available.

9.4.11 Immunological

No data available.

9.4.12 Metabolic

9.4.12.1 Acid-base disturbances

Metabolic acidosis could occur as a result of acidic metabolites (Davis et al., 1997).

9.4.12.2 Fluid and electrolyte disturbances

No data available.

9.4.12.3 Others

No data available.

9.4.13 Allergic reactions

No data available.

9.4.14 Other clinical effects

No data available.

9.4.15 Special risk

No data available.

9.5 Other

No data available.

9.6 Summary

10. MANAGEMENT

10.1 General principles

No data available about treatment of thiodoglycol exposure. The chemical structure of thiodiglycol is similar to that of ethylene glycol (1,2-ethanediol) (HO-CH2-CH2-OH) (Budavari 1996), in that both compounds contain ethanol groups. Both compounds are substrates for the alcohol dehydrogenase enzyme and both compounds forms acidic metabolites (Black et al., 1993, Davis et al., 1997). Based on this information it would be relevant to look at the main treatment options for ethylene glycol.

10.2 Life supportive procedures and symptomatic/specific treatment

Make a proper assessment of airway, breathing, circulation and neurological status of the patient.

Adminster oxygen.

Monitor vital signs.

Monitor acid-base balance.

10.3 Decontamination

No data is available about the absorption time for thiodiglycol. However decontamination by gastric lavage and syrup of ipecac when exposed to ethylene glycol are not beneficial due to the rapidity with which ethylene glycol is absorbed. Neither lavage nor ipecac should be used (Davis et al., 1997).

10.4 Enhanced elimination

Hemodialysis should be employed with a severe acidosis (Davis et al., 1997).

10.5 Antidote treatment

10.5.1 Adults

Treatment with ethanol may prevent some of the toxic effect of the acidic metabolites, since ethanol will compete with thiodiglycol for the enzyme alcohol dehydrogenase. The suggested dosing regimen for intravenous ethanol consists of a loading dose of 10 cc/kg of a 10% ethanol solution followed by a continous infusion of 1.5 cc/kg/h. This may be administered orally or intravenously (Davis et al., 1997).

10.5.2 Children

No data available, see section 10.5.1.

10.6 Management discussion

Activated charcoal poorly absorbs alcohol, it is probably not indicated for thiodiglycol intoxication.

11. ILLUSTRATIVE CASES

11.1 Case reports from the literature

No data available

12. ADDITIONAL INFORMATION

12.1 Specific preventive measures

No data available.

12.2 Other

No data available

13. REFERENCES

Aldrich (1992-1993) Catalog Handbook of Fine Chemicals.

Anslow WP, Karnofsky DA, Jager BV, & Smith HW (1948) The intravenous, subcutaneous and cutaneous toxicity of bis((-chloroethyl) sulfide (mustard gas) and of various derivatives. Journal of Pharmacology and experimental Therapeutics, 93:1-9.

Black RM, Brewster K, Clarke RJ, Hambrook JL, Harrison JM, & Howells DJ (1993) Metabolism of thiodiglycol (2,2'-thiobis-ethanol): isolation and identification of urinary metabolites following intraperitoneal administration to rat. Xenobiotica, 23(5):473-481.

Black RM, Hambrook JL, Howells DJ, & Read RW (1992) Biological fate of sulfur mustard, 1,1'-thiobis(2-chloroethane). Urinary excretion profiles of hydrolysis products and (-lyase metabolites of sulfur mustard after cutaneous application in rats. Journal of Analytical Toxicology, 16(2): 79-84.

Black RM & Read RW (1995) Biological fate of sulphur mustard, 1,1'-thiobis(2-chloroethane): identification of (-lyase metabolites and hydrolysis products in human urine. Xenobiotica, 25(2):167-173.

Budavari S ed. (1996) The Budavari 1996, 12th ed. Merck Research Laboratories, Division of Merck & Co., Inc. Whitehouse Station, NJ, USA.

Carpenter CP & Smyth HF (1946) Chemical burns of the rabbit cornea. American Journal of Ophthalmology, 29:1363-1372.

Davis DP, Bramwell KJ, Hamilton RS, & Williams SR (1997) Ethylene glycol poisoning: case report of a record-high level and a review. The Journal of Emergency Medicine, 15(5):653-667.

Davison C, Rozman RS, & Smith PK (1961) Metabolism of bis-(-chloroethyl sulfide (sulfur mustard gas). Biochemical Pharmacology, 7:65-74.

Lee T, Pham MQ, Weigand WA, Harvey SP, & Bentley WE (1996) Bioreactor strategies for the treatment of growth-inhibitory waste: An analysis of thiodiglycol degradation, the main hydrolysis product of sulfur mustard. Biotechnology Progress, 12(4):533-539.

Lewis RJ (1996) Sax's dangerous properties of industrial materials, 9th ed. Van nostrand reinhold.

Roberts JJ & Warwick GP (1963) Studies of the mode of action of alkylating agents-VI the metabolism of bis-2-chloroethylsulphide (mustard gas) and related compounds. Biochemical Pharmacology, 12:1329-1334.

RTECS- Registry of toxic effects of chemical substances. Issue 98-2 (May, 1998)

Sigma (1998) Biochemicals and reagents for life science research. email: sigma@ibm.net

Smyth HF, Seaton J, & Fischer L (1941) The single dose toxicity of some glycols and derivatives. Journal of Industrial Hygiene and Toxicology, 23(6):259-268.

Somani SM & Babu SR (1989) Toxicodynamics of sulfur mustard. International Journal of Clinical Pharmacology, Therapy and Toxicology, 27(9):419-435.

Union carbide data sheet, 1971. 11:3. Sited in RTECS.

Wils ERJ, Hulst AG, de Jong AL, Verweij A, & Boter HL (1985) Analysis of thiodiglycol in urine of victims of an alleged attack with mustard gas. Journal of Analytical Toxicology, 9(6):254-257.

Wils ERJ, Hulst AG, & van Laar L (1988) Analysis of thiodiglycol in urine of victims of an alleged attack with mustard gas, Part II. Journal of Analytical Toxicology, 12(1):15-19.

14. AUTHOR(S), REVIEWER (S)

Mette Groom Andersen Goodin
Department of Pharmacology
University of Otago
Dunedin, New Zealand

PEER REVIEWED GROUP

Ligia Fruchtengarten, Mahdi Balali-Mood, Wayne Temple, Nigel Langford
Edinburgh September 2001



    See Also:
       Toxicological Abbreviations
       Thiodiglycol (ICSC)
       Thiodiglycol (SIDS)