Probing the relationship between external and internal human exposure of organophosphate flame retardants using pharmacokinetic modelling

• Human external exposure (i.e. intake) of organophosphate flame retardants (PFRs) has recently been quantified, but no link has yet been established between external and internal exposure. In this study, we used a pharmacokinetic (PK) model to probe the relationship between external and internal exposure data for three PFRs (EHDPHP, TNBP and TPHP) available for a Norwegian cohort of 61 individuals from 61 different households. Using current literature on metabolism of PFRs, we predicted the human body burden and compared it to the measured serum and urine data for the PFRs metabolites. Unavailable parameters were estimated using a model fitting approach (least squares method) after assigning reasonable constraints on the ranges of fitted parameters. Results showed an acceptable comparison between PK model estimates and measurements (< 10-fold deviation) for EHDPHP. However, a deviation of 10-1000 was observed between PK model estimates and measurements for TNBP and TPHP. Sensitivity and uncertainty analysis on the PK model revealed that EHDPHP results showed higher uncertainty than TNBP or TPHP. However, there are indications that (1) current biomarkers of exposure (i.e. assumed metabolites) for TNBP and TPHP chemicals might not be specific and ultimately affecting the outcome of the modeling, (2) some exposure pathways might be missing. Further research, such as in vivo laboratory metabolism experiments of PFRs including identification of better biomarkers will reduce uncertainties in human exposure assessment.

Subject headings

NATURVETENSKAP  -- Geovetenskap och miljövetenskap -- Miljövetenskap (hsv//swe)

NATURAL SCIENCES  -- Earth and Related Environmental Sciences -- Environmental Sciences (hsv//eng)

Keyword

flame retardants

human exposure

pharmacokinetic modelling

metabolism

Publication and Content Type

vet (subject category)

ovr (subject category)