A couple of weeks ago I discussed measurement of chemicals in blood and urine and what it actual means; as part of the post I did a quick “back of the envelope” calculation to relate the BPA (bisphenol A) concentrations in urine that had the media so worked up to estimated exposure doses and what regulatory agencies consider to be a safe dose. Well, in the new issue of Regulatory Toxicology and Pharmacology, researchers from the Université de Montréal, Health Canada and Summit Toxicology published a paper attempting the same thing, only using a more rigorous approach. How did my quick calculation stack up?
First, I’ll look at what these researchers actually did. They reviewed the available literature on the toxicity of BPA and limits recommended by regulatory agencies. They also looked at available pharmacokinetic data (data on what happens to BPA in the body), including a few physiologically-based pharmacokinetic (PBPK) models, which are basically sets of mathematical equations describing how a chemical moves between different parts of the body and is metabolized. They also looked at how exposure to BPA could be measured; they concluded that while blood concentrations would be more meaningful, current technology could not measure it at low enough levels, and that the only currently plausible approach is to measure BPA metabolites in urine.
After going through the available studies, they concluded that BPA is almost entirely eliminated in urine (in the form of the metabolite BPA-G) within 24 hours, and that therefore the amount excreted in urine can be related directly to the exposure dose (the same conclusion I reached).
Like me, they ended up doing calculations both for concentrations in urine and the creatinine-adjusted concentrations. I just used a single value for simplicity; this study did separate calculations for children, adolescents, men and women.
The results of their evaluation were actually very similar to my results; they expressed their results as a BPA urinary concentration in ug/g creatinine per ug/kg-d oral dose ranging from 45.8 for adult men to 64.0 for children, with an overall average of 51.0; if I convert my calculations to those units I had a value of 50 (except I didn’t get paid to do it or get publication credits…). So this further supports the measured concentrations in urine corresponding to an average exposure dose approximately 1000 times lower than Health Canada’s estimated “safe” dose.
Of course that still doesn’t address the issue of whether Health Canada’s estimate of the safe dose (or the even higher doses recommended by some other agencies) is appropriate – I’ll try to get to that within the next few weeks.
Krishnan, K., Gagné, M., Nong, A., Aylward, L., & Hays, S. (2010). Biomonitoring Equivalents for bisphenol A (BPA) Regulatory Toxicology and Pharmacology, 58 (1), 18-24 DOI: 10.1016/j.yrtph.2010.06.005