Answer Explanations 3

Most likely mutagenic
Expert 5
Watson paper, Chem Bio Interactions, 1987 is most relevant as the 1,3-D was purified. I believe a strict answer to the above question is that 1,3-D has some mutagenic potential. However, based on the low yield its metabolism to the epoxide, and its detoxification by glutathione, I do not think it poses a mutagenic threat in vivo.
Most likely NOT mutagenic
Expert 14
This view is based on the fact that the mutagenic concern coming from the positive findings in the Ames test is ruled out by clear negative results in appropriate in vivo follow-up studies.
Clearly NOT mutagenic
Expert 1
Clean, state-of-the art in vivo mutagenicity data available. Only potential vulnerability as mentioned earlier may be the selection of the top dose (could probably be better explained)
1 vote 1 0 votes
Expert 5
04/18/2019 12:57

I could not locate the Lawlor refs for the Ames test, so I can't evaluate them. I'd like to get the ref for the clean state of the art mutagenicity data referred to. The Watson paper reported a low, but apparently positive response for highly purified 1,3-D. However, no raw data were included and no dose response data were included. Metabolism of 1.3-D to its epoxide apparently occurs, but is minor pathway. However, the 1,3-D-epoxide is reactive with dG (Schneider, 1998) and based on reactivity of other alkyl epoxides would be expected to react with DNA. Thus, I believe a strict answer to the above question is yes. However, based on the low yield of the epoxide and its detoxification by glutathione, I do not think it poses a mutagenic threat in vivo.

0
Expert 5
04/18/2019 13:41

There is an error in the ref in the above comment - the paper referred to is R.E. Talcott, 1984. The Watson paper does show a clear mutagenic dose response for purified 1,3-D in the presence of metabolic activation, but this greatly reduced by glutathione.

0
Expert 4
04/22/2019 10:07

I too do not think it poses a mutagenic threat in vivo

2 votes 2 0 votes
Expert 3
04/23/2019 13:14

The question is confounded by the lack of context...mutagenic potential in vitro? in vivo? in humans? This may explain the difference in the answers in the original review. I agree that, based on the available data, it is most likely not mutagenic in vivo.

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