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GENOTOXICITY OF 1,3-DICHLOROPROPANE, 2,2-DICHLOROPROPANE, AND L,1-DICHLOROPROPENE IN SALMONELLA AND E. COLI PROPHAGE-INDUCTION ASSAYS
Citation:
Granville, C. A., S H. Warren, G. HugginsClark, S E. George, L D. Claxton, AND D M. DeMarini. GENOTOXICITY OF 1,3-DICHLOROPROPANE, 2,2-DICHLOROPROPANE, AND L,1-DICHLOROPROPENE IN SALMONELLA AND E. COLI PROPHAGE-INDUCTION ASSAYS. Presented at Environmental Mutagen Society Mtg, San Diego, California, March 16-21, 2001.
Description:
Genotoxicity of 1,3-Dichloropropane, 2,2-Dichloropropane, and 1,1-Dichloropropene in
Salmonella and E. coli Prophage-Induction Assays
1,3-Dichloropropane (1,3-DCP), 2,2-dichloropropane (2,2-DCP), and 1,1- dichloropropene (I,I-DCP) have been detected in ground water in as many as 1% of sources. Their introduction to the environment most likely occurs by their presence in many soil fumigant blends. Little toxicological data are available on any of these compounds, but their structural similarity to 1,3-dichloropropene, a known rodent carcinogen, has made them a high priority for research. These compounds are on the 1998 US EP A Contaminant Candidate List and were deemed "high priority for research" in 1999. Thus, we are determining the genotoxicity of these compounds in Salmonella, using a pre-incubation assay, and in the E. coli prophage-induction assay. The role of glutathione-S-transferase (GST) in the activation of 1,3-DCP has also been investigated based on a 1985 study that reported positive results in TA1535 with metabolic activation. Our preliminary results show that both 1,3-DCP and 2,2-DCP are weakly mutagenic without metabolic activation in the prophage-induction assay, whereas 1,I-DCP is negative. Likewise, preliminary tests in Salmonella strains TA98, TA100, and TA1535 of2,2-DCP and 1,I-DCP were negative; 1,3-DCP was also largely nonmutagenic in these strains. However, a weak positive response to 1,3-DCP was observed in TA1535 at 8,850 uM in the presence of S9. Preliminary tests for activation of 1,3-DCP by GST in RSJ100 (TA1535 expressing rat GST5-5) and TA1535 expressing human GSTT1-1 were negative. These results suggest that 1,I-DCP is not mutagenic, whereas 1,3-DCP and 2,2-DCP can cause DNA damage that induces prophage. Thus, 1,3-DCP and 2,2-DCP may cause DNA strand breaks, which would induce prophage, but would not revert the Salmonella strains used here. Future work involves testing 1,I-DCP and 2,2-DCP in RSJ100 and determining optimal doses of 1,3-DCP and GSH concentrations in tests for GST activation.
Abstract does not necessarily represent policy of the US EPA.