Response to Comment on “Enhanced Elimination of

University of Queensland, National Research Centre for Environmental Toxicology, 39 Kessels Road, Coopers Plains, Queensland 4108, Australia. Environ...
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Correspondence/Rebuttal pubs.acs.org/est

Response to Comment on “Enhanced Elimination of Perfluorooctane Sulfonic Acid by Menstruating Women: Evidence from Population-based Pharmacokinetic Modeling”

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e thank Verner and Longnecker1 for their insightful comments on the rate of menstrual blood serum loss (Gmbl, mL/kg-bw/year). We agree with the authors that the parameter Gmbl is subject to uncertainty and that there are limited literature available for characterizing the composition and volume of menstrual fluid loss. In our paper,2 we assumed that monthly menstrual blood serum loss is 36 mL/month, which amounts to 432 mL/year and Gmbl = 6.1 mL/kg-bw/year, assuming a body weight of 71 kg. During our uncertainty and sensitivity analysis, we assigned Gmbl a confidence factor of 1.2, meaning we assumed a 95% probability that volume of serum loss is in the range 360 to 518 mL/year. However, Verner and Longnecker1 estimated that menstrual serum loss is 868 mL/year which is 2 times greater than our assumption of 432 mL/year and outside the range of our uncertainty analysis. We reran our model with the rate of menstraul blood serum loss suggested by Verner and Longnecker1 (i.e., Gmbl = 12.2 mL/kg-bw/year, hereafter referred to as the ”adjusted Gmbl”). The optmized intrinsic elimination half-life for women when Gmbl = 12.2 mL/kg-bw/year is 4.3 years, with a confidence interval (CI) of 4.1−4.5 years. This half-life is 1.1 times longer than when assuming Gmbl = 6.1 mL/kg-bw/ year (i.e., 4.0 years, with CI of 3.8 to 4.2 years). The adjusted intrinsic half-life for women when we double the Gmbl (i.e., 4.3 years) is closer to, but still different from, the instrinsinc half-life for men, which is 4.7 years with a CI of 4.5−5.0 years. We therefore stand by the conclusion of Wong et al.2 that menstruation alone cannot explain the discrepancy in elimination of PFOS between men and women. When using the adjusted Gmbl, menstruation would explain 60% of the

difference in the elimination rate of PFOS between men and women. Figure 1 shows the modeled data fits well to the measured data when the adjusted Gmbl is applied. When we plotted the modeled vs measured data using the adjusted Gmbl, the root mean squared error (RMSE) = 0.04, which is smaller than the RMSE estimated from the Gmbl of Wong et al.,2 that is, 0.05. Finally, we acknowledge the lack of information for parametrizing Gmbl and are therefore grateful for Verner and Longnecker’s1 contribution. In the absence of even newer information on the rate of menstrual fluid loss, we will use the corrected parametrization of Verner and Longnecker1 in any future human pharmacokinetic modeling studies.

Fiona Wong*,† Matthew MacLeod† Jochen F. Mueller§ Ian T. Cousins† †



Department of Environmental Science and Analytical Chemistry, Stockholm University, Svante Arrhenius väg 8, SE-10691, Stockholm, Sweden § University of Queensland, National Research Centre for Environmental Toxicology, 39 Kessels Road, Coopers Plains, Queensland 4108, Australia

AUTHOR INFORMATION

Corresponding Author

*E-mail: fi[email protected]. Notes

The authors declare no competing financial interest.

Figure 1. Modeled and measured PFOS concentration in serum for women using the adjusted Gmbl (12.2 mL/kg-bw/year) and Wong et al.,2 Gmbl (6.1 mL/kg-bw/year).

© XXXX American Chemical Society

A

DOI: 10.1021/acs.est.5b00981 Environ. Sci. Technol. XXXX, XXX, XXX−XXX

Environmental Science & Technology



Correspondence/Rebuttal

REFERENCES

(1) Verner, M.; Longnecker, M. P. Comment on “Enhanced elimination of perfluorooctane sulfonic acid by menstruating women: evidence from population-based pharmacokinetic modeling” Pharmacokinetic parameters for menstrual fluid volume and composition. Environ. Sci. Technol. 2015, DOI: 10.1021/acs.est.5b00187. (2) Wong, F.; MacLeod, M.; Mueller, J.; Cousins, I. T. Enhanced elimination of perfluorooctane sulfonic acid by menstruating women: evidence from population-based pharmacokinetic modeling. Environ. Sci. Technol. 2014, 48, 8807−8814.

B

DOI: 10.1021/acs.est.5b00981 Environ. Sci. Technol. XXXX, XXX, XXX−XXX