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Endpoint:
additional toxicological information
Type of information:
other: publication
Adequacy of study:
supporting study
Study period:
1996
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The publication has sufficient information for interpretation of results.
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Cytotoxic and Non-cytotoxic Effects of the MEIC Reference Chemicals on Spontaneously Contracting Primary Cultured Rat Skeletal Muscle Cells
Author:
M. Gulden and H. Seibert
Year:
1996
Bibliographic source:
Toxicology in Vitro 10 (1996) 395-406

Materials and methods

Type of study / information:
Study was designed to evaluate the suitability of a multi-endpoint test system using primary cultured spontaneously contracting rat skeletal muscle cells to indicate an acute neuro- and/or cardiotoxic potential of chemicals. The concentration-dependent effects of the 50 MEIC (Multicenter Evaluation of In Vitro Cytotoxicity) reference chemicals on contractility, indicative of the functional integrity of the electrically active muscle cell membrane, were determined.
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
None
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
Sodium chloride
EC Number:
231-598-3
EC Name:
Sodium chloride
Cas Number:
7647-14-5
Molecular formula:
ClNa
IUPAC Name:
sodium chloride
Details on test material:
None

Results and discussion

Any other information on results incl. tables

The EC50 values obtained for the sodium chloride for inhibition of spontaneous contractility (24 hr) was 74,000µM, cytolethal activity (CK depletion after exposure for 24 hr) was 110,000µM and alteration (reduction) in glucose consumption was 160,000µM. Results are presented in Table 2.

Several of the test compounds were applied as hydrochlorides or salts with chloride, sulfate, phosphate or nitrate as anionic or sodium and potassium as cationic components. The low potency of sodium chloride (EC0 values > 74 mM) proves (a) that the effects measured with the hydrochlorides of amitriptyline, dextropropoxyphene, propranolol, thioridazine, verapamil and orphenadrine were due to the drugs themselves; (b) that the effective components of potassium and mercuric chlorides were the K+ and Hg’+ cations, and (c) that the effects of sodium fluoride were caused by the Fluoride anion.

Applicant's summary and conclusion

Conclusions:
The EC50 values obtained for the sodium chloride for inhibition of spontaneous contractility (24 hr) was 74,000µM, cytolethal activity (CK depletion after exposure for 24 hr) was 110,000µM and alteration (reduction) in glucose consumption was 160,000µM.

Executive summary:

This study was designed to evaluate the suitability of a multi-endpoint test system using primary cultured spontaneously contracting rat skeletal muscle cells to indicate an acute neuro- and/or cardiotoxic potential of chemicals. The concentration-dependent effects of the 50 MEIC (Multicenter Evaluation of In Vitro Cytotoxicity) reference chemicals on contractility, indicative of the functional integrity of the electrically active muscle cell membrane, were determined. Additionally, effects on two other endpoints, glucose consumption and viability, were monitored to reveal whether alterations in contractility were associated with cytotoxicity. In total, 30 of the tested compounds inhibited contractility at non-cytotoxic concenfrations. The contractility-inhibiting and cytotoxic potencies differed by factors of more than 10 in the case of diazepam, phenol, propranolol, phenobarbital, mercuric chloride, thioridazine, verapamil, chloroquine, quinidine, phenytoin and atropine, of more than I00 in the case of amitriptyline, dextropropoxyphene, orphenadrine and amphetamine, and even more than 1000 for nicotine. On the basis of the available knowledge of the acute toxic effects and modes of acute toxic action of the test compounds, this characteristic response pattern is shown to be highly predictive for compounds reported to be cardio cardio and/or neurotoxic owing to interference with excitable membrane functions and/or neurotransmission.

The EC50 values obtained for the sodium chloride for inhibition of spontaneous contractility (24 hr) was 74,000µM, cytolethal activity (CK depletion after exposure for 24 hr) was 110,000µM and alteration (reduction) in glucose consumption was 160,000µM.