Answer Explanations 6
I have sufficient confidence that exposures to 1,3-D are unlikely to pose a carcinogenic risk to humans. However, it is important to point out that there may be debate around certain tumors (as seen in the peer review comments) including whether the B6 lung mouse tumors are intrinsically the result of the high/variable background or treatment related. If treatement related, the most plausible explanation is that a high treatment concentration of 1,3-D may be stimulating the growth of the spontaneous lesions given that the response is late onset, benign, and at a site with a high historical background incidence. So, even if this response is treatment related, the nature of the response itself (as described in 5.8) is of questionable human relevance due to the strain/sex specific genetic susceptibility and the concentration at which it occurred is not relevant to actual human exposures (ie exceeded the KMD).
The results reviewed are fairly conclusive, but as indicated above, 1) they must be extrapolated to humans, 2) results could be different in other animal species, 3) no tests were reported on fetal exposures, 4) human blood levels in highly exposed individuals were not available, 5) SNP's in GSH in humans need to be considered.
I don't think the arguments for the classification have been made with sufficient rigor in the White Paper, but the data described offer reasonable support.
I offer a "6" for the actual answer I wanted to give ("possibly carcinogenic")-- for the answer I was constrained to give ("suggestive"), I'd rate my confidence at an 8-- there is a wealth of "suggestive" evidence, and while each of the exculpatory theories offered in the white paper would dissuade me from ever concluding 1,3-D is "likely," none of it lowers my appraisal below "suggestive" to "not likely." ADDENDUM ADDED MAY 1 BASED ON ROUND 4: I have changed my degree of confidence from 6 to 9 based on Round 4. "Not likely" (the opposite of my view then) has become in my mind even less credible as I read and engaged with the other comments.
One can never be fully confident when relying on animal to human extrapolation with an imperfect data set. Relatively speaking, the evolution of the data on this chemical over a decade or more of testing has provided answers to questions of the data and has suggested little reason for concern for a human carcinogenic hazard under conditions of exposure well below those tested in animals.
Same reasons as given in response to question 5.8