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μg/kg-day or μg/day? A commentary on Georgopoulos et al., JESEE 2008

Journal of Exposure Science & Environmental Epidemiology volume 18, page 535 (2008)Cite this article

Georgopoulos et al. (JESEE, 26 March 2008; doi:10.1038/jes.2008.9) have carried out an impressive analysis of the problem of reconstructing population exposures to environmental chemicals from biomarkers. However, they have focused on chlorpyrifos (CPF) using a definition of dose rate (μg intake per day) that is only indirectly related to human health. The measures of exposure that are more directly related to systemic health effects (e.g., not dermal chloracne) are the intake dosage in μg/kg body weight as a single bolus and μg/kg-day that corresponds to the units of the US EPA chronic reference dose (RfD) for CPF (Klaassen, 2008). The patient body weight is an important variable in studies of the systemic health effects of exposures to pesticides, such as CPF, because the concentration in the blood produced by the intake dose is inversely proportional to the subject's blood volume that is approximately proportional to body weight. Although the NHEXAS study that the authors simulated may not have recorded weight of food consumed per day, they did know the subjects' body weights (Pang et al., 2002). Then, using the IOM (2007) estimate of daily caloric intake (kcal/kg body weight) required for maintaining that body weight, a function of a subject's known age and gender, they could have simulated the relative amounts of kcal (and food) their subjects consumed.

This need to normalize the intake dose by the subject's body weight was recognized in Nolan et al. (1984) and Timchalk et al. (2002) that the authors cited and in the non-cited articles about CPF uptake and clearance by Shurdut et al. (1998), Griffin et al. (1999) and Oliver et al. (2000). Klaassen (2008, p. 20) gives an example of how cholinesterase inhibition, a systemic health effect of CPF, is linearly related to the logarithm of bolus intake dosage of CPF in units of mg/kg body weight. Therefore, without considering the subjects' body weights, one cannot tell from the authors' results expressed as μg intake per day which simulated subject in their cohort is at the greatest risk of a CPF health effect (the highest μg/kg-day) or even if anyone is at or above the current EPA chronic RfD for CPF of 0.3 μg/kg-day (http://www.epa.gov/oppsrrd1/REDs/chlorpyrifos_ired.pdf).

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    David T Mage

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Mage, D. μg/kg-day or μg/day? A commentary on Georgopoulos et al., JESEE 2008. J Expo Sci Environ Epidemiol 18, 535 (2008). https://doi.org/10.1038/jes.2008.52

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