Sodium hydrogensulphide

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

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

Adequacy of study:

weight of evidence

Reliability:

other: Klimisch scoring not applied for lack of relevance for toxicokinetic data.

Rationale for reliability incl. deficiencies:

other: Well documented study.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Detoxication of sodium s-sulfide in the rat.

Author:

Curtis, C.G.; et al.

Year:

1972

Bibliographic source:

Biochem. Pharmacol. 21, 2313-2321

Materials and methods

Objective of study:

absorption

distribution

excretion

metabolism

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

This study investigated the distribution and fate of administered sodium 35-S-sulfide and forms part of a wider investigation of the metabolic activity of reduced sulphur compounds in-vivo. (i) M.R.C. hooded rats (3 male and 3 female) were administered 0.5 µmol/0.5 ml sulfide (per 200 g bw). One group received the dose oral and another i.p. Urine was collected after 12, 24 and 48 hours of exposure. Faeces were collected for 48 hours.
(ii) Two male rats were exposed intravenously to the same dose. Their urine and bile was collected in intervals of an hour over a period of six hours.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Disodium sulphide

EC Number:

215-211-5

EC Name:

Disodium sulphide

Cas Number:

1313-82-2

Molecular formula:

Na2S

IUPAC Name:

disodium sulfide

Details on test material:

- Name of test material (as cited in study report): sodium 35-S-sulphide
- Substance type: technical product
- Physical state: solid
- Locations of the label (if radiolabelling): 35 S-sulfide
OTHER
- test substance obtained from Radiochemical Centre, Amersham, Bucks, England
No further information on test material was stated.

Radiolabelling:

yes

Remarks:

35-S sulfide

Test animals

Species:

rat

Strain:

other: M.R.C.

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 4- 6 weeks (young rats) and adult rats
- Weight at study initiation: 30 - 50 g bw (young rats) and 200 - 300 g bw (adult rats)
- Individual metabolism cages: yes

Administration / exposure

Route of administration:

other: oral and intraperitoneal injections

Vehicle:

other: 0.154M phosphate buffer

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
Oral injections/ Intraperitoneal injections/intravenously
5 µmoles sodium 35-S sulfide in 0.5 mL of 0.154 M phosphate buffer, pH 7.4 per 200 g body weight

Duration and frequency of treatment / exposure:

no data

Doses / concentrations

Remarks:

Doses / Concentrations:
(i) and (ii) 5 µmoles sodium 35-S sulfide in 0.5 mL of 0.154 M phosphate buffer, pH 7.4 per 200 g body weight

No. of animals per sex per dose / concentration:

(i) 3 males and 3 females each for oral and intraperitoneal incetion
(ii) 2 males

Control animals:

not specified

Details on dosing and sampling:

Dosing and sampling:
Experiment I:
- animals were under ether anaesthesia while receiving the injections (oral or intraperitoneal)
- post administration, the animals were subsequently placed in metabolic cages designed to permit separate collection of urine and faeces
- in experiment (i): urine samples were collected into hydrogen peroxide at intervalls of 12, 24, and 48 hours after injection and then frozen
- in experiment (i): faeces were collected into ammoniacal peroxide for 48 hr, water was added and the mixture centrifuged in order to remove the debris; the pooled supernatant of 3 extractions was frozen
- in experiment (i): in a separate series of experiments the urines were collected into n-ethylmalmeimide for 24 hr; samples were subjected to paper chromatography and paper electrophoresis

Experiment II:
- in experiments were urine and bile were collected via ureter and bile duct cannulae, animals were first lightly anaesthetised with ether, the jugular vein was cannulated and phenobarbitone injected via the cannula
- sodium 35-S sulfide was administered intravenously with bile duct and ureter cannulae
- urine and bile was collected into N-ethylmaleimide at hourly intervals over a 6 hour period
- urine and bile samples were assayed for total 35-S; urines were also subjected to thin-layer chromatography and paper electrophoresis

Method type(s) for identification:
- Paper chromatography on Whatman No. 1 chromatographic paper
- Paper electrophoresis: 5 - 10 µL samples on Whatman No. 1 paper in 0.1 M sodium acetate-acetic acid buffer, pH 4.5 with 8 v/cm
- Thin-layer chromatography: 5 µl sample applied to silica-gel plates and chromatograms were developed in a saturation chamber
- Cellulose acetate membrane electrophoresis: 2 µl samples were applied to cellulose acetate membranes and subjected to horizontal electrophoresis for 2 hr in a barbitone buffer, 50 - 70 mM, pH 8.6
- Detection of radioactive areas on chromatograms and electrochromatograms with a Packard Model 7200 radiochromatogram scanner and the relative amount of radioactivity associated with each area was estimated from the record of the scanner. Alternatively, radioactive areas were located by radioautography on X-ray films.
- Whole-body radioautography (as described by Powell, Curtis and Dodgson (1967)
- Measurement of radioactivity in a Beckman, Model LS 100 scintillation spectrometer; for measurement of total 35-S in blood and plasma, samples were dissolved in NaOH, diluted and counted; standards were prepared by adding known amounts of 35-S to blood or plasma; for measurement of trichloroacetate-insoluble 35-S samples, samples of blood and plasma were added to trichloroacetate, the percipitate resuspended 3x and the final percipitate dissolved in NaOH

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:

experiment (ii):
- Specific tissues in which sulfide oxidises could not be determined.
- Nevertheless, the results showed that radioactivity was very persistent in blood.

Details on excretion:

experiment (i):
- After i.p. (1.95 mg/kg??) and oral administration of sodium 35S-sulfide, 84-93 and 52-69 %, respectively appeared in the urine over the 48 hr experimental period, the major proportion appearing during the first 12 hr.
- The chromatograms and electropherograms obtained from the 24 hr urine samples showed one major radioactive component with a mobility identical to that of inorganic 35S-sulfate.
- Only trace amounts of other 35S-labelled materials were detected.

experiment (ii):
- After six hours 45% of the administered 35S was recovered from the urine and 4.7-5.0% was recovered from the bile.
- Thus, the main faith of sodium sulfide administered via the routes described is oxidation to sulfate and excretion via the urine.

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

experiment (i):
- The chromatograms and electropherograms obtained from the 24 hr urine samples showed one major radioactive component with a mobility identical to that of inorganic 35S-sulfate.

experiment (ii):
- the main faith of sodium sulfide administered via the routes described is oxidation to sulfate and excretion via the urine.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): other: The following conclusions can be drawn: after oral administration of sulfide to rats almost 70% are excreted within 48 hrs, 63% via urine and the remainder via faeces. Sulfides are absorbed rapidly and extensively.
The following conclusions can be drawn: after oral administration of sulfide to rats almost 70% are excreted within 48 hrs, 63% via urine and the remainder via faeces. Sulfides are absorbed rapidly and extensively.

Executive summary:

Read-across from Na2S to NaHS:

Given that sodium sulfide and sodium hydrogensulfide dissociate in aqueous media, it can safely be assumed that under most physiologically relevant conditions ( i.e., neutral pH) sulfide and hydrogen sulfide anions are present at almost equimolar concentrations, thus facilitating unrestricted read-across between both species. Only under extreme conditions such as gastric juice (pH << 2), sulfides will be present predominantly in the form of the non-dissociated hydrogen sulfide. In turn,hydrogen sulfide (H₂S) may be formed from both soluble sulfides, according to the following equilibria:

                           Na₂S + H₂O   →  NaOH + NaHS (2Na⁺/ OH^-/ HS^-)

                           NaHS + H₂O  →  NaOH + H₂S (Na⁺/ OH^-/ H₂S)

Similarly, hydrogen sulfide dissociates in aqueous solution to form two dissociation states involving the hydrogen sulfide anion and the sulfide anion, according to the following equilibrium:

                           H₂S  ↔  H⁺  +  HS^-  ↔  2 H⁺  +  S^2-

In conclusion, under physiological conditions, inorganic sulfides or hydrogensulfides as well as H2S will dissociate to the respective species relevant to the pH of the physiological medium, irrespective the nature of the “sulfide”, which is why read-across between these substances and H2S is considered to be feasible without any restrictions.