Believe the differences in opinion stem from weighing the validity and strength of assays differently. The definition I applied to 'mutagenic' was broader than as in 'gene mutation', including 'chromosome mutations', and this is where a see a certain weakness of the data package. Regarding the last question: Not sure where this is going. The in vivo assays are done in order to provide insights on in vivo genotoxicity potential which seems all relevant for risk assessment. Yes, some of the endpoints looked at may be more relevant than others but in the given context I don't believe one assay trumps it all
Yes, actually the question itself leads to misinterpretations. I considered in question 2.6 the overall conclusion of 1-,3-D in terms of gene mutation induction, bearing also in mind that question 2.7 was dealing with the clastogenic potential of 1,3-D. Referring to the same question, after it was re-phrased, and the EPA framework for weighing evidence for a mutagenic mode of action (MOA) in which the term "mutagenic" indicates the capacity of either the carcinogen or its metabolite to react with or bind to DNA in a manner that causes mutations (gene mutations and structural chromosome aberrations, both in vitro and in vivo) I would judge 1,3-D as equivocal. As reported from my side in round 2, I considered the induction of gene mutation of no concern, since the positive findings in the Ames test and mammalian cell mutation assays (Myhr and Caspary, 1991) were ruled out by the negative findings obtained, mainly by the Big Blue rat study, via oral route (Young 2018). However, the concern for clastogenicity is not ruled out neither in vitro nor in vivo with the available data-set. The quoted mouse bone marrow micronucleus test by Gollapudi (1985) with a negative outcome, cannot be considered reliable in relation to the absence of a clear demonstration of target tissue exposure (e.g. no reduction of %PCE). In addition, its relevance is further limited by additional shortcomings which include an unjustied difference in the percentage of PCE in the negative control group between male and female animals and within female animals at 24- and 48-hour sampling times and by a limited statistical sample (1000 PCE/animal). Furthermore, the bone marrow micronucleus test doesn't seem to represent an adequate in vivo follow-up assay for IARC carcinogenic haloalkanes and haloakenes which are genotoxic in vitro as shown by Morita et al. (1997), Mutation Research 389,3–122. On the other hand, I would mention the positive results observed in different organs in the alkaline single cell gel electrophoresis (comet) assay after treatment with 1,3-D (Sasaky et al., 2000). In this study 1,3-D, when the substance was injected intraperitoneally to mice, induced marked and statistically significant increases in DNA breakage in the stomach, liver, kidney, blood, lung, brain and bone marrow three hours after treatment. Notably, the effect observed in bone marrow, though significantly different from the untreated control was marginally affected compared to the other organs/tissues. Histopathological observation excluded the presence of signs of necrosis in the organs in which DNA damage was observed. This last observation is further strengthened by the negative findings observed in the same organs at the 24-hour sampling time. The study, even though not OECD compliant, is in my opinion sufficiently reliable and therefore clastogenicity cannot be excluded and cannot be ruled out by the negative findings obtained in the bone marrow micronucleus test (Gollapudi 1985) for the reasons discussed before.
I interpreted mutagenic as the ability to induce mutations in ANY mutational assay (bacterial, cell culture, in vivo). If the question was interpreted as only for an in vivo assay, then I would have indicated "clearly not mutagenic". If the question referred to humans I would have answered most likely not mutagenic, since the in vivo mutagenic assay by Young, was clearly negative, yet 1,3-D showed some activity the Ames test, albeit much less when highly purified and the most recent peer-reviewed article I could find (Eder E, 2006) did not include dose-response data, or statistical significance.