Magnesium dihydrogen disulphite

Neurotoxicity

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: Short communication on sodium bisulphite toxicity to human neuroblastoma cells.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Toxicity of chloroprocaine and sodium bisulfite on human neuroblastoma cells.

Author:

Seravalli, E.; Lear, E.

Year:

1987

Bibliographic source:

Anesth. Analg. 66, 954-958

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Plates of human neuroblastoma cells were incubated with sodium bisulphite concentrations in the range from 0.08 to 0.8 mM at pH 7.4 for 3 or 20 hours. After the exposure, the medium was discarded and drug-free medium was added to the experimental and control cultures. The cultures were left undisturbed at 37˚C for 3, 6, and 9 days. Thereafter, the cultures were washed with saline and stained with Wright-Giemsa for cell counting. Cell multiplication was measured by the number of colonies that developed in each experimental and untreated culture.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Sodium hydrogensulfite

EC Number:

231-548-0

EC Name:

Sodium hydrogensulfite

Cas Number:

7631-90-5

Molecular formula:

NaHSO3

IUPAC Name:

sodium hydrogensulfite

Details on test material:

- Name of test material (as cited in study report): sodium bisulfite
- Molecular formula (if other than submission substance):NaHSO3
- Molecular weight (if other than submission substance): 104 g/mol
- Substance type: technical product
- Physical state: solid, white powder
- Other: sodium bisulfite was obtained from two commercial sources, hencefore identified as SB-1 and SB-2
No further details are given.

Test animals

Species:

other: not applicable, in-vitro test

Strain:

other: not applicable, in-vitro test

Details on test animals or test system and environmental conditions:

not applicable, in-vitro test

Administration / exposure

Route of administration:

other: not applicable, in-vitro test

Vehicle:

other: not applicable, in-vitro test

Details on exposure:

- sodium bisulfite was diluted in serum-free medium (DMEM-vide supra)
- dilution were made as follows: SB concentrations ranging from 0.08 mM to 0.8 mM
- dilutions of all drugs were prepared immediately before addition to the cells

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

3 or 20 hours

Frequency of treatment:

not applicable

Doses / concentrations

Remarks:

Doses / Concentrations:
0.08 - 0.8 mM sodium bisulfite
Basis:
nominal conc.

No. of animals per sex per dose:

not applicable, in-vitro test

Details on study design:

- Dose selection rationale: the concentrations were chosen within limits that approximate the concentrations achieved in clinical practice

Examinations

Statistics:

Reduction of colony forming ability was determined by expressing the number of colonies in drug-treated cultures as a percentage of the number of colonies in its control culture. Inhibition was considered definite when it was ≥25 %. Student’s t-test (two-tailed) was used for statistical analysis. P values <0.05 were considered statistically significant.

Results and discussion

Results of examinations

Clinical signs:

not examined

Mortality:

not examined

Body weight and weight changes:

not examined

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Clinical biochemistry findings:

not examined

Behaviour (functional findings):

not examined

Gross pathological findings:

not examined

Neuropathological findings:

not examined

Effect levels

Dose descriptor:

NOAEL

Remarks on result:

not determinable

Remarks:

no NOAEL identified

Any other information on results incl. tables

- Sodium bisulphite reduced the cell multiplication in neuroblastoma cells.

- The colony-forming ability (CFA) was inhibited by 72% to 92% at a 3-h exposure to one commercial sample of sodium bisulphite and by 57% to 72% with another sample (both tested at concentrations of 0.8 mM).

- no difference in the inhibition of CFA was detected between both commercial samples at concentrations below 0.8 mM

- Prolongation of exposure time to 20 hours resulted in a CFA inhibition of 98% by both samples.

- cells exposed to either sample of sodium bisulfite for 20 hr did not resume ability to form colonies during the study period of 9 days

- The authors concluded that sodium bisulphite may have neurotoxicity of potential clinical significance because it is used as antioxidant in commercial solutions of chloroprocaine.

Applicant's summary and conclusion

Conclusions:

In this study sodium bisulfite was found to have an inhibitory effect on CFA of neuroblastoma that varied with concnetration and exposure time. Cell multiplication in human neuroblastoma cells was reduced by sodium bisulfite treatment (0.08-0.8 mM) for 3 or 20 hours.