Induction of micronuclei in Syrian hamster embryo cells: comparison to results in the SHE cell transformation assay for national toxicology program test chemicals

New investigations into the genotoxicity of cobalt compounds and their impact on overall assessment of genotoxic risk

“…There are several published papers all indicating induction of MN (Van Goethem et al, 1997;De Boeck et al, 2003a;Miller et al, 2001;Olivero et al, 1995;Gibson et al, 1997), and possibly also CA (Olivero et al, 1995), by soluble cobalt salts and ultrafine metal cobalt. These effects were often seen at moderate or low levels of cytotoxicity and do not appear to be artefacts of excessive toxicity.…”

“…However, the MN response with cobalt chloride was flat (a plateau) whilst toxicity (mitotic inhibition) increased with concentration, making it difficult to evaluate the results. On the other hand, Ponti et al (2009) did not detect induction of MN in Balb/3T3 cells by concentrations of cobalt chloride up to 10 mM, while Gibson et al (1997) reported doserelated induction of MN in Syrian hamster embryo (SHE) cells treated with cobalt sulphate for 24 h in the absence of metabolic activation.…”

Toxicological Profile for Ethylbenzene

“…Ethylbenzene also failed to induce sister-chromatid exchanges in Chinese hamster ovary cells (NTP 1986(NTP , 1999 or chromosomal aberrations in Chinese hamster cells (NTP 1986(NTP , 1999 or rat liver cells (Dean et al 1985). A positive dose-related increase in the occurrence of micronuclei formation were observed in Syrian hamster embryo cells tested at ethylbenzene concentrations of 25-200 µg/mL (Gibson et al 1997). A significant increase in morphological cells transformations was also observed in Syrian hamster embryo cells exposed to 150 or 200 µg/mL for 7 days (Kerckaert et al 1996); the 200 µg/mL concentration resulted in significant cytotoxicity.…”

“…Similarly, in vitro genotoxic assays in mammalian cells were negative when noncytotoxic concentrations were used (Dean et al 1985;McGregor et al 1988;NTP 1986NTP , 1999Seidel et al 2006;Wollny 2000). However, some studies did not cause genotoxic alterations at concentrations not associated with cytotoxicity (Chen et al 2008;Gibson et al 1997); it is not known whether these positive results reflect a genotoxic response in a particular test system or whether they are outliers. Independent confirmation or refutation of these studies, as well as further genotoxicity studies, especially in mammalian systems, would help provide clarification of these conflicting results.…”

Test No. 487: In Vitro Mammalian Cell Micronucleus Test

“…Cultured primary human or other mammalian peripheral blood lymphocytes (7) (20) (46) (54) have been used for micronucleus testing but at this time have not been extensively validated. Therefore the use of those cell lines and types should be justified based on their demonstrated performance in the test, as described in the Acceptability Criteria section.…”