SciPi 145: Peer review of the genotoxicity, toxicokinetics, and carcinogenicity of a pesticide
Is it possible that exposure of a fetus, via a pregnant mother could lead to genotoxic effects in the fetus? Should in vitro tests for genotoxic effects of 1,3-D be carried out in human cells?
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(3 Answers)
Expert 5
The first question as expressed, is a general one, but there is ample evidence in experimental animals that in utero exposure to genotoxic carcinogens can cause cancer in offspring. There is certainly evidence in humans that maternal exposure to certain chemicals can lead to permanent damage in offspring, such as, in the cases of ethanol, thalidomide, and DES. The effects of these compounds may not result from genotoxicity, but they illustrate that chemicals with a wide variety of physico-chemical properties can pass from pregnant woman to fetus. There seems to be no obvious reason why 1,3D should be an exception.
Expert 1
No, unless a repeat somatic cell clastogenicity test would lead to a clear pos response. There are no described cases for a germ cell only mutagen
Expert 14
This cannot be excluded.
Concerning the in vitro tests for genotoxic effects of 1,3-D, I would strongly recommend the performance of a robust in vitro micronucleus test in human lymphocytes (OECD TG 487).
Expert 2
04/18/2019 09:37The first comment above (user553126 [Expert 5] ) is right on target, and suggests that the original question could be broadened to ask "is it possible that 1,3D is a developmental toxin, whether via a genotoxic mechanism or any other mechanism?"
Expert 7
04/18/2019 09:40Although not summarize in the White paper, it appear from other documents that there is little indication that 1,3-D poses a reproductive toxicity or teratogenic risk. Thus, given the negative findings in the in vivo DNA adduct/mutation studies and the dominant lethal test (recognizing peer review comment on lack of sensitivity) as well as the lack of concern for reproductive/developmental toxicity, there is not a scientific justification to pursue this line of testing based on available evidence. (as stated above "unless a clear clastogen" and then issue would have to be re-visited )
Expert 2
04/18/2019 13:34To user 232578 [Expert 7] -- probably not our place to say, but if an important question (developmental tox) has been "answered" outside of the White Paper, then it would seem to be a good idea for the White Paper to reflect that (negative) evidence, with references.