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Genetic toxicity: in vitro

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Administrative data

genetic toxicity in vitro
Type of information:
experimental study
Adequacy of study:
supporting study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Review of available data

Data source

Reference Type:
review article or handbook
Genotoxicity under Extreme Culture Conditions. A Report from ICPEMC Task Group 9
Scott D, Galloway SM, Marshall RRM Ishidate M, Brusick D, Ashby J & Myhr BC
Bibliographic source:
Mutation Research, Vol. 257, No. 2, pages 147-205

Materials and methods

Principles of method if other than guideline:
The influence of extreme culture conditions upon the results of in-vitro genotoxicity assays and their relevancy to in-vivo studies were discussed. Extreme culture conditions discussed included excessively high concentrations of test agents, high levels of cytotoxicity, the use of metabolic activation systems, and extremes of pH.

Test material

Constituent 1
Chemical structure
Reference substance name:
Sulphuric acid
EC Number:
EC Name:
Sulphuric acid
Cas Number:
Molecular formula:
sulfuric acid

Results and discussion

Test results
The authors report positive results in in vitro studies in cultured mammalian cells due to low pH

Any other information on results incl. tables

A variety of studies have shown that in-vitro assays that indicate a high level of apparent genotoxic activity in which very high concentrations of test agent were used do so because of the effect of elevated osmolality of the culture medium. To avoid this problem in in-vitro clastogenicity tests, the maximum concentration of the test agent should be kept below 10 millimolar. Many studies have shown that when rodent models have been used for human genotoxicity, rodent genotoxicants can only be detected in in-vitro systems in which concentrations that are highly cytotoxic are used. It has not been possible to define an upper limit for cytotoxicity in in-vitro tests other than on a case by case basis. Liver S9 mix has been shown to exert genotoxic effects in some in-vitro test systems, especially those based on mammalian cells. Assays that utilize metabolic activation systems derived from isolated microsomes appear to be capable of generating toxic and mutagenic species. This is attributed to their being susceptible to lipid peroxidation. The use of nonphysiological pHs in in-vitro test systems can not only affect the mutagenic response of the test agent but can be mutagenic in their own right. Studies with sulphuric acid reporting negatve results in Ames tests and positive results in chromosomal aberration studiens in CHO cells and in a non-standard assasy in developing sea-urchin embryos are reported; the positive findings in these studies are considered to be a consequence of the low pH of the culture medium.

Applicant's summary and conclusion


The authors conclude although the artefactual genotoxicity associated with the use of extreme culture conditions does not explain all of the discrepancy between in-vitro and in-vivo results, modifying test protocols to eliminate these conditions should help improve the credibility and reliability of in-vitro tests for predicting in-vivo responses.
Executive summary:

Positive results in studies of chromosomal aberration seen with sulphuric acid are considered to be a consequence of effects on the pH of the culture medium.