The in vivo tests are conclusive for non-tumorigenicity of 1,3-D in rodents. However, additional testing could change this opinion. One can always devise additional tests (e.g., lifetime exposure, diffferent rodent strains, knockout mice, tests in non-human primates, tests on fetuses where mothers were exposed) .There is always the possibility some people will have SNP's rendering them more susceptible to genotoxins. So it can't be ruled out entirely that certain individuals with excessive exposure could have a substantial risk from 1,3-D.
Expert 11
04/18/2019 02:35My conclusion was further strengthened by the data on genotoxicity and toxicokinetics and the significant reduction in bw gain in Scott. Is there an explanation for the reduced bw gain ?
Expert 14
04/19/2019 04:34To user 477751 [Expert 11]
Genotoxicity on the "negative side" is not supported by solid data and results. On the contrary, there are evidences that 1,3-D could be clastogenic as shown by the in vivo Comet assay in stomach, liver, kidney, bladder, lung , brain and bone marrow (Sasaki et al., 1998). In addition, aneugenicity , which I believe to be not a real issue, cannot be ruled out by the available studies.
Expert 7
04/19/2019 06:11As stated, it woud be helpful to clarify the issue of clastogenicity with additional information to increase confidence. But it is still my opinion, this deficiency does not distract from the "not likely to be carcinogenic" conclusion because of the totality of the evidence (lack of gene mutations in vivo, TK, cancer bioassay results, etc). Clarifying the issue of aneuploidy, in my opinion, is more important in the context of reproductive risk. However, in this case, it appears that 1,3-D does not pose reproductive/developmental risk from the results of traditional TGs (as discussed in other documents). I agree with the comment that the White paper needs to include discussion of these studies that may have bearing on this issue.
Expert 4
04/22/2019 11:12I agree with user-232578 [Expert 7] that while clarification of the issue of clastogenicity might provide increased confidence about the carcinogenicity of 1,3-D it falls into what I might term "nice but not necessary" studies as it would not likely change the bottom line conclusion of "not likely to be carcinogenic"