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An in vitro and an in vivo unscheduled DNA synthesis assay with a zinc oxide/ hexachloroethane (Zn/HCE) smoke

BIBRA International, Woodmansterne Road, Carshalton, Surrey SM5 4DS

SD Blowers

BIBRA International, Woodmansterne Road, Carshalton, Surrey SM5 4DS

TC Marrs

Chemical and Biological Defence Establishment, Porton Down, Salisbury, Wiltshire, SP40 50Q, UK

P. Rice

Chemical and Biological Defence Establishment, Porton Down, Salisbury, Wiltshire, SP40 50Q, UK

1 Since Zn/HCE smoke has been shown previously to be weakly positive in the Ames test, and negative in the bone marrow micronucleus assay, other assays including a second in vivo assay examining unscheduled DNA synthesis (UDS) in rat hepatocytes has been carried out, as recommended by the UK Department of Health guide lines.

2 Zn/HCE smoke was assessed for its ability to induce DNA repair in an UDS assay both in vitro in cultured rat hepatocytes and in rat hepatocytes after in vivo treatment by inhalation.

3 For the in vitro investigation, two studies were carried out assessing media exposed to Zn/HCE smoke using at least seven concentrations up to a toxic level. At the highest concentration of Zn/HCE smoke, where some viable cells were seen, an increase in UDS was observed in both experiments. However this was not statistcally significant, was only seen at a level where toxicity was observed and was therefore considered not to be biologically significant.

4 In the in vivo investigation, one study was carried out in three separate parts, assessing two doses of Zn/HCE smoke characterised by their zinc content as approxi mately 20 and 56 µg l ^-1 air. A dose-related increase in UDS was observed which was not statistically sig nificant. The positive control behaved as anticipated, showing a highly statistically significant response. 5 It was concluded that Zn/HCE smoke did not induce unscheduled DNA repair in the in vitro or in vivo UDS assays under the conditions used in the studies. The overall lack of genotoxic effect of this smoke in this and previous studies in this laboratory would not suggest a major health hazard.

Key Words: zinc oxide/hexachloroethane smoke • DNA repair • UDS assay • rats

Human & Experimental Toxicology, Vol. 15, No. 1, 38-44 (1996)
DOI: 10.1177/096032719601500107


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