2.11
Are the available in vivo and in vitro studies adequate or is there a need to consider genotoxicity data for structural surrogates? How should data from structural surrogates be used? (please explain)
Results
(3 Answers)
Answer Explanations
- ConsideredExpert 14
Structurally related aloalkenes (e.g. vinyl bromide) are genotoxic and carcinogenic.
- IgnoredExpert 5
It’s hard to think of a good surrogate. 1,3-D is such a small molecule that almost any change will likely alter its reactivity substantially. Substitution at the CH2 would likely be the most conservative. I found a couple of refs to 1,3,3-TC-propene. It was inactive in MN assay, in vivo and in vitro, but produced strand breaks in vitro. This doesn't really add much to considerations about 1,3-D and I don’t think any other structural surrogate would add anything useful.
- ConsideredExpert 1
Can be considered, yes, but I don't think that for a data rich compound (with some controversial findings) as is the case here data from structural analogs would add much to the discussion
Debate (3 Comments)
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Expert 4
my thinking is aligned with answer 1 above and I do not think that consideration of structural surrogates will contribute significantly to the WOE analysis during risk assessment
Expert 5
Hard to find a good surrogate. 1;3-D is such a small molcule that almost any change will alter it's reactivity. Substitution at the CH2 would likely be the most conservative. I found a couple of refs to 1,3,3-TCpropene. Inactive
in mn assay, in vivo and in vitro, but produces strand breaks in vitro. Doesn't really much to discussion.
Expert 5
Should be an "add" before "much" in the above cooment.