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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
supporting study
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:
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

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: flakes
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 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:
(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 fate 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.