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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1936
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: only secondary literature

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1936
Report date:
1936

Materials and methods

Objective of study:
distribution
other: Absorption after oral uptake... (see attached file)
Test guideline
Qualifier:
no guideline required
Principles of method if other than guideline:
Evaluation of a toxikokinetic study: Hug, E.: Absorption and disappearance of the test substance from the blood after administration intravenously or by stomach tube.
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Sodium hydroxymethanesulphinate
EC Number:
205-739-4
EC Name:
Sodium hydroxymethanesulphinate
Cas Number:
149-44-0
Molecular formula:
CH4O3S.Na
IUPAC Name:
sodium hydroxymethanesulphinate
Details on test material:
no data given in the toxicokinetic study
Radiolabelling:
not specified

Test animals

Species:
dog
Strain:
not specified
Sex:
not specified
Details on test animals or test system and environmental conditions:
no data given in the toxicokinetic study

Administration / exposure

Route of administration:
other: oral application by stomach tube, intravenous injection
Vehicle:
water
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:
see table 1


PREPARATION OF DOSING SOLUTIONS:

DIET PREPARATION
- Rate of preparation of diet (frequency):
- Mixing appropriate amounts with (Type of food):
- Storage temperature of food:

VEHICLE
- Justification for use and choice of vehicle (if other than water):
- Concentration in vehicle:
- Amount of vehicle (if gavage):
- Lot/batch no. (if required):
- Purity:

HOMOGENEITY AND STABILITY OF TEST MATERIAL:
Duration and frequency of treatment / exposure:
8 h
Doses / concentrations
Remarks:
Doses / Concentrations:
intravenous injection (dosing volume): 10 c.c/kg, gavage via digestive tract (volume): 20 c.c/kg
No. of animals per sex per dose / concentration:
intravenous injection (6 animals): animals #1 and #2: 0.1 g/kg;
animals # 3and # 4: 0.2 g/kg;
animals # 5 and # 6: 0.5 g/kg

application by stomach tube :
animals #7 and #8: 0.2 g/kg;
animals #9 and # 10: 0.5 g/kg;
animals # 11 and # 12: 1g/kg(see table 2)
Control animals:
no
Positive control reference chemical:
no
Details on study design:
no data given in the toxicokinetic study given
Details on dosing and sampling:
no data given in the toxicokinetic study given
Statistics:
no data given in the toxicokinetic study given

Results and discussion

Preliminary studies:
no preliminary study was conducted.
Main ADME resultsopen allclose all
Type:
other: Absorption after oral uptake:
Results:
most of injected substance disappeared from blood within < 2 h & practically all disappeared within 5 h.
Type:
other: Absorption after dermal exposure:
Results:
no relevant dermal absorption
Type:
other: Absorption after inhalation:
Results:
uptake by inhalation may be only relevant after exposure to dusts of the substance (systemic absorption)
Type:
distribution
Results:
fast distribution into blood, plasma & water based body fluids is expected after systemic absorption
Type:
distribution
Results:
transfer to lipophilic body parts is highly unlikely
Type:
metabolism
Results:
no metabolites identified

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Absorption after oral uptake:t ests revealed very slow resorption from the digestive tract after application by stomach tube such that its bioavailability was too low for antidote effectiveness
Absorption after dermal exposure: dermal absorption of this substance is not expected
Absorption after inhalation: The uptake by inhalation may be only relevant after exposure to dusts of the substance when particles are small enough to pass the tracheal airways down to the alveoli.
Solubilisation of solid Sodium formaldehyde sulfoxylate in surfactant fluid may then be expected together with systemic absorption.
Details on distribution in tissues:
Due to its strong hydrophilicity, a fast distribution after systemic absorption into blood, plasma and further water based body fluids is to be expected as long as biological membranes do not inhibit such distribution.
A transfer to any lipophilic compartments of the human body is highly unlikely, the fact of which clearly indicates a very low potency for bioaccumulation.

After parenteral application to dogs the substance disappeared from the blood in less than 2 hours and practically all disappeared within 5 hours (see above).
Details on excretion:
most of the substance was excreted renally (up to 68 % within 8 hours after intravenous application).

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study results
after intravenous injection the concentration of the test item in the blood plasm decreased rapidly. The main elimination took place via renal way in the first two hours. The total elimination was stated to be between 48.9 and 67.9 %.
After gavage via digestive tract the concentration in the blood plasm can be stated as proportional to the given doses.The total elimination was stated to be between 7.4 and 33.1 %
Executive summary:

Absorption:

Absorption after oral uptake:

Hug, E. performed tests with dogs for sodium formaldehyde sulfoxylate`s afficacy to be used as an antidote against Mercury poisoning.

These tests revealed very slow resorption from the digestive tract after application by stomach tube such that its bioavailability was too low for antidote effectiveness.

After intravenous injection of sodium formaldehyde sulfoxylate most of it disappeared from the blood in less than 2 hours and practically all disappeared within 5 hours.

 

Absorption after dermal exposure:

Sodium formaldehyde sulfoxylate is an organic salt which is highly soluble in water.

On the other hand human epidermis is an excellent barrier for salts, in particular since highly water soluble and charged molecules can not (easily) penetrate such barrier.

Therefore any relevant dermal absorption of this substance is not expected.

 

Absorption after inhalation:

Sodium formaldehyde sulfoxylate is a solid with a melting point of 64 °C; its boiling point cannot be determined, because the substance decomposes at the melting point.

The uptake by inhalation may be only relevant after exposure to dusts of the substance when particles are small enough to pass the tracheal airways down to the alveoli.

Solubilisation of solid Sodium formaldehyde sulfoxylate in surfactant fluid may then be expected together with systemic absorption.

Distribution:

This substance is highly soluble in water (> 1,000 g/L).

Due to its strong hydrophilicity, a fast distribution after systemic absorption into blood, plasma and further water based body fluids is to be expected as long as biological membranes do not inhibit such distribution.

A transfer to any lipophilic compartments of the human body is highly unlikely, the fact of which clearly indicates a very low potency for bioaccumulation.

 

After parenteral application to dogs the substance disappeared from the blood in less than 2 hours and practically all disappeared within 5 hours (see above).

 

Metabolism:

Metabolites of Sodium formaldehyde sulfoxylate were not identified in the experiments with dogs (see above), but most of the substance was excreted renally (up to 68 % within 8 hours after intravenous application).

This simple excretion pattern is plausible, since very hydrophilic substance do not need metabolic conversion for excretion, i.e. Sodium formaldehyde sulfoxylate can be directly renally eliminated.

Excretion:

Excretion of (unchanged) Sodium formaldehyde sulfoxylate from the body is fast and obviously does not need any metabolic conversion due to its high water solubility.