Answer Explanations 4

Strongly agree
Expert 6
I agree with the conclusion. The NTP (National Toxicology Program) (1985) studies (Toxicology and carcinogenesis studies of Telone II (technical grade 1,3-dichloropropene containing 1% epichlorohydrin as a stabilizer) in F344/N rats and B6C3F1 mice (gavage studies). U.S. Dept. of Health and Human Services, Technical Report Series No. 269. ) used Telone II as the test material and it contained epichlorhydrin, a known mutagen and carcinogen to rodents, and humans (see https://doi.org/10.1016/0165-1110(81)90016-6).
Strongly agree
Expert 5
Only positive responses are at high doses, probably exceeding saturation of GSH.
Agree
Expert 11
The case could be made even stronger if the potency of epichlorohydrin can explain tumor incidences in the NTP studies. There were other chemcials such as trichloroethene that were stabilized with epichlorohydrin and were tested by NTP in the 1970 and 80s. The tumor profile and inciences there may be used for further support. What are the other components of the products in 1,3-dichloropropene tested by NTP ? I have more confidence in the newer guideline-compliant studies to inform on the carcinogenicity of 1,3-D since they used a better defined product without a mutagenic stabilizer. In addition, the NTP studies have design and conduct issues that hamper interpretation of the findings
Strongly agree
Expert 9
I agree. I see no reason to consider questionable data when other more definitive data are available.
0
Expert 6
04/17/2019 16:52

Just a comment, both the old and new formulations of 1,3 D are called Telone II. It has not been informed if old Telone II and new Telone II formultions have the same concentration of 1,3D. It is also not known what is the concentration of 1,3 D in DD92, which has been used in rat experiments. Could anyone inform this, please?

0
Expert 6
04/17/2019 16:54

We could also discuss about the potency of epichlorohydrin. Are you aware of any carcinogenesis study with epichlorohydrin alone?

2 votes 2 0 votes
Expert 11
04/18/2019 02:21

The white paper includes a reference on a study with epichlorohydrin. I am aware that epichlorohydrin was used as a stabilizer in other chemicals that were tested by NTP in the 1970s (eg. trichloroethene). It could help to check doses of epichlorohydrin in these studies and correlate to tumor response in the target liver.

1 vote 1 0 votes
Expert 11
04/18/2019 02:24

Information on composition of the different Telone II formulations including impurities would be helpful to interpret the inconsistent results in the newer studies (Scott et al., and Kelly et al.)

2 votes 2 0 votes
Expert 2
04/18/2019 13:28

To users 477751 [Expert 11] and 915125 [Expert 6] : my (long) comment on Topic 5.5 (WOE subpanel) presents cancer slope factor estimates from the bioassays of epichlorohydrin alone, and in my opinion STRONGLY suggests that the 1% impurity was far too small an amount to account for the excesses in tumors in the NTP bioassays of 1,3D-- *especially* the female bladder carcinomas, since epichlorohydrin has never been found to increase this tumor type.

1 vote 1 0 votes
Expert 9
04/18/2019 14:12

I appreciate the comment by 37600 [Expert 2] to the effect that a 1% concentration of epichlorohydrin was too small to have resulted in the tumor incidences observed in the NTP studies. However, we don't know anything about the potential interaction between the 1% contaminant and the 1,3-D. In addition, we have other bioassays in which there was no possible interaction between these substances. Why would we not believe the results of these unconfounded bioassays as opposed to speculating about the possible contribution of the 1% contaminant in the NTP bioassays.

2 votes 2 0 votes
Expert 2
04/18/2019 14:35

To user-750802 [Expert 9] -- you raise a good question but I think one logical answer is "because positive findings have more weight than negative ones, unless/until the positive findings are EXPLAINED satisfactorily." If all we needed to dismiss, say, an epidemiology study with a relative risk of 5 is another one with a RR of 1 (or 0.5), then we would have failed to act on many "known" causes of human disease. You're correct that it's possible that all the positive findings in the NTP bioassays are explained by the impurity, but I'm just pointing out how weak that explanation seems to me-- especially w/respect to the female mouse bladder tumors.

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