Please provide one question you would like to have the cancer bioassay expert panel members answer (please be sure to put your response in the form of a question).

How does the TK information affect your opinion of the long term bioassay results, particularly for those not confounded by co-exposure to epichlorhydrin?

Can you draw any insights from the inconsistencies in results between F344 (diet) and CD (gavage) studies where the dose to targets arguably could have been higher in the negative (CD) study? Is this simply a reflection of strain differences or can we say anything about dose-rate effects and toxicity?

EPA and other competent regulatory agencies around the world recognize that advances in biology and computer science provide opportunities to make the risk assessment process more informative and efficient than is currently possible with traditional approaches, largely based on animal bioassays. These have been described in a variety of notices following the NAS's 2007 report "Toxicity Testing in the 21st Century, A Vision and a strategy" and are beginning to be formalized (e.g., OECD AOP program https://www.oecd.org/chemicalsafety/testing/adverse-outcome-pathways-molecular-screening-and-toxicogenomics.htm). How, and to what extent, do you recommend that such approaches be applied to further evaluate carcinogenic potential and increase confidence in the conclusion that 1,3-D is not likely to be carcinogenic to humans?

Since the carcinogenicity of 1,3-D has been in question for more than 30 years, and every one of the 8 lifetime bioassays to date is subject to some degree of controversy, would it not be helpful to conduct a state-of-the-art bioassay, by inhalation (the predominant human exposure route), using a current commercially-available formulation, that could resolve these doubts one way or the other? (for example, with larger sample sizes at doses of 5 and 20 ppm, to have sufficient power to detect small excesses if they exist)

Should 1,3-D be tested in non-human primates?

Please comment on the White paper interpretation of the inhalation chronic bioassays by Stott 1987 (mice) and Lomax 1987 (rats). In your response, please comment on whether the increase incidence of bronchioavleolar tumors in male mice should be regarded as treatment related. If the your response is treatment-related, do you agree it is a weak response at the highest dose tested in males only. Please comment on whether this response should be considered as relevant or not for human health risk assessment.