US EPA

1312136 

Journal Article 

Abstract 

Secondary metabolites of di-n-butyl phthalate (DnBP) and di-iso-butyl phthalate (DiBP) in urine as valuable biomarkers of exposure 

Koch, HM; Kafferlein, H; Zur, NA; Bruning, T 

2008 

Yes 

Epidemiology
ISSN: 1044-3983
EISSN: 1531-5487 

19 

6 

S281 

English 

10.1097/01.ede.0000340319.19320.95 

WOS:000260191901257 

Background:
Di-n-butyl phthalate (DBP) and di-iso-butyl phthalate (DiBP) are widely used in consumer products, enteric-coated tablets and as plasticizers for polymers. DnBP and DiBP are metabolized in humans to their monoesters mono-n-butyl phthalate (MnBP) and mono-iso-butyl phthalate (MiBP). These primary metabolites are currently used in human biomonitoring approaches to assess internal exposures. However, the simple monoesters are prone to external contamination and have rather short half-times of elimination. These shortcomings could be overcome using oxidized, secondary metabolites, when applicable.

Methods:
We investigated 160 spot urine samples (partly repeated from 110 volunteers) with no known occupational phthalate exposures for oxidised metabolites of both isomers with oxo-, hydroxy- and carboxy-functional groups. 3-carboxy-MPP (3cxMPP) was detected in 90% of the samples with a median concentration of 0.66 μg/L (95th percentile [95P]: 2.70 μg/L). 3-cxMPP is a metabolite of DnBP but also of other higher molecular weight phthalates, thus not specific to DnBP exposure.

Results:
3cxMPP was comparably weakly correlated with MnBP (r = 0.56; P < 0.001) and weaker with MiBP (r = 0.30; P < 0.001). 3-hydroxy-MnBP (3OH-MnBP) was detected in 97% of the samples with a median of 1.73 μg/L (95P: 13.3 μg/L). 3OH-MnBP was highly correlated (r = 0.91; P < 0.001) with MnBP (median: 20.9 μg/L; 95P: 110.7) but excreted at about 10-fold lower concentrations. Regarding oxidised DiBP metabolites we detected OH-MiBP in all samples and at high concentrations (median: 10.5 μg/L; 95P: 119.4 μg/L). OH-MiBP was highly correlated with MiBP (r = 0.90; P < 0.001) and excreted at roughly half the concentration of MiBP (median: 27.3 μg/L; 95P: 193.0 μg/L). Thus, OH-MiBP is an excellent additional biomarker of DiBP exposure, supplementing MiBP. With limits of quantification of 0.1 μg/L for all metabolites, we detected no metabolites with a keto (oxo) functional group.

Conclusion:
Overall, our findings suggest that there are considerable differences in DiBP and DnBP metabolism which have to be taken account of when interpreting biomonitoring data. 

ISEE 20th Annual Conference 

Pasadena, CA 

October 12-16, 2008