Thiodiglycol

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to OECD guideline 417 with acceptable restrictions (parenteral application; exhalation of radioactivity not measured).

Data source

Reference

Reference Type:

publication

Title:

Metabolism of thiodiglycol (2,2'thiobis-ethanol): isolation and identification of urinary metabolites following intraperitoneal administration to rats.

Author:

Black RM, Brewstar K, Clarke RJ, Hambrook JL, Harrison JM, Howells DJ

Year:

1993

Bibliographic source:

Xenobiotica 23: 473-481

Materials and methods

Objective of study:

excretion

metabolism

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 417 (Toxicokinetics)

Deviations:

yes

Remarks:

(i.p. injection)

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Thiodiglycol

EC Number:

203-874-3

EC Name:

Thiodiglycol

Cas Number:

111-48-8

Molecular formula:

C4H10O2S

IUPAC Name:

2-[(2-hydroxyethyl)sulfanyl]ethan-1-ol

Details on test material:

1) 35S-labelled thiodigylcol, activity ca. 6 mCi/mM
2) doubly-labelled thiodiglycol (35S & 13C4; ratio 1:1)

Radiolabelling:

yes

Remarks:

see below

Test animals

Species:

rat

Strain:

other: Porton

Sex:

male

Details on test animals or test system and environmental conditions:

Body weight 250-300 g
singly in metabolism cages
no further data

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

other: TS dissolved in propylene glycol-ethanol ( 1 :1 v /v)

Duration and frequency of treatment / exposure:

Single i.p. injection

Doses / concentrations

Remarks:

Doses / Concentrations:
see freetext

No. of animals per sex per dose / concentration:

4 males

Control animals:

no

Positive control reference chemical:

no

Details on study design:

Injection volume: 1 ml/kg bw

Details on dosing and sampling:

see freetext

Statistics:

Means +- standard error (n=4)
no further data

Results and discussion

Preliminary studies:

no data

Toxicokinetic / pharmacokinetic studies

Details on absorption:

no data

Details on distribution in tissues:

no data

Details on excretion:

see freetext below

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

see freetext below

Any other information on results incl. tables

1) Approximately 60% of the administered dose was excreted in the urine within 6 h and ca. 90% of the administered within 24 h, independently of the amount applied; after 8 days virtually all of the dose had been excreted via urine (93-99%, no dose dependency); no significant excretion in the faeces.

2) Four metabolites were isolated by HPLC and identified by MS (structural assignment by comparison with authentic synthetic standards).
Thiodiglycol sulphoxide was the major metabolite accounting for ca. 90% of the excreted radioactivity following the i.p. injection of 13C4,35S-thiodigylcol;
S-(2-hydroxyethylthio)acetic acid was present in significant quantities up to 10%; thiogylcol sulphone and S-(2-hydroxyethylsulphinyl)acetic acid were identified as minor metabolites. Analysis for thiodigycol by GC-MS indicated that ca. 0.5-1.0% of the administered dose was excreted unmetabolized. No data were given on exhaled CO2.

Authors discussion of putative pathways: TS is mainly oxidized at the sulphur atom resulting in thiodiglycol sulphoxide and (after further oxidation) the minor metabolites thiodiglycol sulphone and S-(2-hydroxyethylsulphinyl)acetic acid (further oxidation at the carbon atom) were observed; another possible pathway is the oxidation of the TS at an carbon atom resulting in S-(2-hydroxyethylthio)acetic acid and (after further oxidation at the sulphur atom) also S-(2-hydroxyethylsulphinyl)acetic acid.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results
In rats ca. 90 % of i.p. injected thiodiglycol is metabolized and excreted via urine within 24 hours after application. The major metabolite detected in urine is thiodiglycol sulphoxide.

Executive summary:

Comparable to OECD guideline 417 with acceptable restrictions (parenteral application; exhalation of radioactivity not measured).

Metabolism and excretion after i.p. injection was studied in male Porton rats. For the determination of the excretion profile, rats received i.p. 35S-radiolabed thiodiglycol at doses of 24 µg/kg bw to 40 mg/kg bw. Ca. 60 % of the administered dose was excreted via urine within 6 hours, ca. 90 % within 24 hours and virtually all of the dose within 8 days (93 - 99 %), independently of the amount injected. No significant excretion was detected in the faeces.

For isolation and identification of metabolites, rats were i.p. injected with 40 mg/kg bw doubly labelled 13C4,35S-thiodiglycol. Samples of pooled urine were analyzed 6 and 24 hours after injection and then daily for 8 days. Thiodiglycol sulphoxide was the major metabolite (oxidation at the sulphur atom) accounting for ca. 90 % of the excreted radioactivity. S-(2-hydroxyethylthio) acetic acid was present in significant quantities up to 10 %; thiodigylcol sulphone and S-(2- hydroxyethylsulphinyl)acetic acid were identified as minor metabolites. Only 0.5 - 1.0 % of the administered dose was excreted unmetabolized.

Conclusion: In rats ca. 90 % of i.p. injected thiodiglycol is metabolized and excreted via urine within 24 hours after application. The major metabolite detected in urine is thiodiglycol sulphoxide.