Temporal Variability in Urinary Phthalate Metabolite Excretion Based on Spot, Morning, and 24-h Urine Samples: Considerations for Epidemiological Studies

Urinary phthalate excretion is used as marker of phthalate exposure in epidemiological studies. Here we examine the reliability of urinary phthalate levels in exposure classification by comparing the inter- and intrasubject variation of urinary phthalate metabolite levels. Thirty-three young healthy men each collected two spot, three first-morning, and three 24-h urine samples during a 3-month period. Samples were analyzed for the content of 12 urinary metabolites of 7 different phthalates. Variability was assessed as intraclass correlation coefficients (ICC). For the metabolites of diethyl-, dibutyl-, and butylbenzyl-phthalates moderate ICCs were observed in all three sample types, albeit highest in 24-h urine (0.51-0.59). For the metabolites of di(2-ethylhexyl) phthalate and di-iso-nonyl phthlates lower ICCs (0.06-0.29) were found. These low ICCs indicate a high risk of misclassification of exposures for these two phthalates in population studies and hence an attenuation of the power to detect possible exposure-outcome associations. The only slightly higher ICCs for 24-h pools compared to first-morning and spot urine samples does not seem to justify the extra effort needed to collect 24-h pools.