3 ms·

I'm a bit unsure what to think. From the article: > "When you have the same kind of findings repeated ... and you keep coming up with the same finding, I think

by tqi 6y ago

I'm a bit unsure what to think. From the article: > "When you have the same kind of findings repeated ... and you keep coming up with the same finding, I think you can begin to say that the data is pretty clear" But also: > By 2019, more than 30 studies had examined prenatal exposure to different types of phthalates ... Not all of the papers had found consistent results, especially in the area of cognitive development, but the report's authors said that might be due to difference in study designs and children's ages. While this finding certainly seems plausible, and the credentials of the project members are impeccable, I am a bit suspicious that they may simply be evaluating a large number of chemicals across a wide range of outcomes, and reporting on the noise. Is there a theory on what the causal mechanism for these chemicals to cause these neurological conditions are?

wittyreference 6y ago
A couple. Some basic neuro papers have found that it's directly neurotoxic. Others have found that it exacerbates the neurotoxicity of certain other compounds (e.g., lead). And other studies have found that pthalate exposure increases urinary output of quinolinic acid, a neurotoxic metabolite of the tryptophan metabolic pathway to which pthalates are structurally similar. This suggests a couple of things: (1) that pthalates are neurotoxic via the excitotoxic pathway that quinolinic acid acts through, and (2) that pthalates induce higher quinolinic acid production (we've confirmed this is true in humans). Essentially, we've confirmed pthalates to be neurologically harmful in a number of animal studies, found a candidate pathway, and confirmed that that pathway is in fact affected in the prediction direction in humans experimentally exposed to higher doses of pthalates. (That last bit slipped by the ethics boards because there are meds that already include pthalates, so patients were randomized to get higher- or lower- pthalate containing formulations of the med, which were otherwise equivalently dosed.) It's a pretty reasonable conclusion at this point, if one isn't already wedded to the idea of the compound's safety.
- tqi 6y ago
  Very interesting, thanks for the explanation!

by tqi 6y ago

wittyreference 6y ago

A couple. Some basic neuro papers have found that it's directly neurotoxic. Others have found that it exacerbates the neurotoxicity of certain other compounds (e.g., lead). And other studies have found that pthalate exposure increases urinary output of quinolinic acid, a neurotoxic metabolite of the tryptophan metabolic pathway to which pthalates are structurally similar. This suggests a couple of things: (1) that pthalates are neurotoxic via the excitotoxic pathway that quinolinic acid acts through, and (2) that pthalates induce higher quinolinic acid production (we've confirmed this is true in humans). Essentially, we've confirmed pthalates to be neurologically harmful in a number of animal studies, found a candidate pathway, and confirmed that that pathway is in fact affected in the prediction direction in humans experimentally exposed to higher doses of pthalates. (That last bit slipped by the ethics boards because there are meds that already include pthalates, so patients were randomized to get higher- or lower- pthalate containing formulations of the med, which were otherwise equivalently dosed.) It's a pretty reasonable conclusion at this point, if one isn't already wedded to the idea of the compound's safety.

tqi 6y ago
Very interesting, thanks for the explanation!