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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Neurotoxicity

Currently viewing:

Administrative data

Endpoint:
neurotoxicity
Remarks:
other: in-vitro
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Very detailed investigation on the mechanism of sulphite toxicity.
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
A mechanism of sulfite neurotoxicity.
Author:
Zhang, X.; et al.
Year:
2005
Bibliographic source:
J. Biol. Chem. 279, 43035-43045

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
In this study the increase in reactive oxygen species (ROS) was assayed in Neuro-2a, PC12, HepG2 cell lines and human foetal liver cells exposed to 5-500 µM freshly prepared sulphite for 30 min was examined.
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Reference substance name:
sodium sulfite
IUPAC Name:
sodium sulfite
Constituent 2
Reference substance name:
Sodium sulphite
EC Number:
231-821-4
EC Name:
Sodium sulphite
Cas Number:
7757-83-7
IUPAC Name:
disodium sulfite
Constituent 3
Reference substance name:
sodium sulfite
IUPAC Name:
sodium sulfite
Details on test material:
- Name of test material (as cited in study report): sodium sulfite
- Molecular formula (if other than submission substance): Na2SO3
- Molecular weight (if other than submission substance): 126 g/mol
- Other: sodium sulfite was obtained from Merck, Germany
No further information given.

Test animals

Species:
other: in-vitro system, rat brain mitochondria used were prepared from Wistar rats
Strain:
other: not applicable
Sex:
not specified
Details on test animals or test system and environmental conditions:
not applicable

Administration / exposure

Route of administration:
other: not applicable
Vehicle:
other: not applicable
Doses / concentrations
Remarks:
Doses / Concentrations:
5-500 µM sodium sulfite
Basis:
other: in-vitro applied concentration
No. of animals per sex per dose:
not applicable

Results and discussion

Results of examinations

Clinical signs:
not examined
Description (incidence and severity):
not applicable
Mortality:
not examined
Description (incidence):
not applicable
Body weight and weight changes:
not examined
Description (incidence and severity):
not applicable
Food consumption and compound intake (if feeding study):
not examined
Description (incidence and severity):
not applicable
Food efficiency:
not examined
Description (incidence and severity):
not applicable
Water consumption and compound intake (if drinking water study):
not examined
Description (incidence and severity):
not applicable
Ophthalmological findings:
not examined
Description (incidence and severity):
not applicable
Clinical biochemistry findings:
not examined
Description (incidence and severity):
not applicable
Behaviour (functional findings):
not examined
Description (incidence and severity):
not applicable
Gross pathological findings:
not examined
Description (incidence and severity):
not applicable
Neuropathological findings:
not examined
Description (incidence and severity):
not applicable
Other effects:
not examined

Effect levels

Dose descriptor:
NOAEL
Remarks on result:
not determinable
Remarks:
no NOAEL identified

Any other information on results incl. tables

- Exposure of Neuro-2a, PC12, HepG2 and human foetal liver cells to micromolar concentrations of sodium sulphite caused an increase in reactive oxygen species and a decrease in ATP.

- Likewise, the biosynthesis of ATP in intact rat brain mitochondria from the oxidation of glutamate was inhibited by micromolar concentrations of sulphite.

- The glutamate-driven respiration increased the mitochondrial membrane potential, and this was abolished by sulphite, but the increases of the potential by malate and succinate were not affected.

- Sulphite inhibits the formation of NADH from exogenous NAD and glutamate added to rat brain mitochondrial extracts.

- Pre-incubation of mitochondria with sulphite blocked the reduction of NAD.

- Glutamate dehydrogenase in rat brain mitochondrial extracts was inhibited dose-dependently by sulphite as was the activity of a purified enzyme.

- The authors proposed that the glutamate dehydrogenase is one target of action of sulphite, leading to a decrease in α-ketoglutarate and a diminished flux through the TCA cycle accompanied by a decrease in NADH through the mitochondrial electron transport chain, a decreased mitochondrial membrane potential, and a decrease in ATP synthesis. 

 

Applicant's summary and conclusion

Conclusions:
In the described study, exposure of Neuro-2a, PC12, HepG2 and human foetal liver cells to 5-500 µM sodium sulfite caused an increase in reactive oxygen species and a decrease in ATP. Sulfite inhibited dose-dependently the glutamate dehydrogenase (GDH) in rat brain mitochondrial extracts. It was concluded that the GDH inhibition by sulfite leads to a decrease in α-ketoglutarate and a diminished flux through the TCA cycle accompanied by a decrease in NADH through the mitochondrial electron transport chain, a reduction in the mitochondrial membrane potential, and a decreased ATP synthesis.