Kinetics of the phthalate metabolites mono-2-ethylhexyl phthalate (MEHP) and mono-n-butyl phthalate (MnBP) in male subjects after a single oral dose.
Level 4 - case-series / case-control
Uncontrolled single-arm human experimental pharmacokinetic study in 4 volunteers.
PubMed 27091076 · doi:10.1016/j.toxlet.2016.04.009
What was done
Four healthy male volunteers aged 23 to 58 years received a single oral dose of deuterium-labeled phthalate monoesters: 50 µg/kg body weight of D4-MEHP or 10 µg/kg body weight of D4-MnBP. Urinary concentrations of parent monoesters and their secondary metabolites were measured up to 46 hours post-administration to establish excretion profiles and elimination half-lives.
What was found
For D4-MEHP, >90% of each metabolite was excreted in urine within 22 hours, with the average excretion of D4-MEHP and four secondary metabolites totaling 62% of the dose (peak secondary metabolite D4-5cx-MEPP at 15%). The mean elimination half-life of D4-MEHP was 3.5 ± 1.4 hours. For D4-MnBP, total urinary recovery ranged from 52% to 130%. Parent D4-MnBP represented 92% of the ingested dose with a half-life of 1.9 ± 0.5 hours, whereas secondary metabolites D4-3OH-MnBP and D4-3cx-MPP constituted 7.1% and 1.0%, respectively.
Why it matters
These data describe the human metabolism and excretion kinetics of direct phthalate monoester exposure, demonstrating rapid urinary elimination and kinetic properties comparable to parent dialkyl diesters.
Limits
The sample size was extremely small (n = 4) and limited to adult males. The study assessed a single oral dose rather than chronic environmental exposure, and total urinary recovery for D4-MnBP showed substantial inter-individual variability (52% to 130%).
Cited by
- supports Phthalates are cleared by the human body within 12 to 24 hours depending on the compound.