Urinary Phthalates and Leukocyte Telomere Length: An Analysis of NHANES 1999–2002

• NHANES 1999–2002 analysis of phthalate metabolites (MEHP, MEP. MBP, and MBzP) and leukocyte telomere length (LTL)
• MEHP was associated with longer LTLs evidence of a dose–response relationship.
• Analyses stratified by age groups, sex and smoking confirmed the association of the MEHP with longer LTL.
• An association between MBP and MBzP with higher LTL was found in the 60 years and older participants.Mono-(2-ethyl)-hexyl phthalate (MEHP) is a metabolite of di-2-ethylhexyl phthalate (DEHP) and recently the International Agency for Research on Cancer (IARC) classified DEHP as “possibly carcinogenic to humans” (Group 2B). Also, the National Toxicology Program list DEHP as “reasonably anticipated to be a human carcinogen.” The associations between MEHP and longer leukocyte telomere length (LTL) found in all age groups may potentially suggest a role of this compound as tumor promoter. However, further studies, such as prospective studies, are needed to more fully understand the implications of the findings of this study.

The International Agency for Research on Cancer classified the di-2-ethylhexyl phthalate (DEHP) as “possibly carcinogenic to humans”. In vitro studies reported that phthalate exposure resulted in induction of several nuclear transcription factors that are activators of telomerase reverse transcriptase (TERT) and telomerase activity of the human telomerase complex. The objective of this study was to determine whether there is an association between urinary phthalate metabolites [mono-ethyl phthalate (MEP), mono-butyl phthalate (MBP), mono-(2-ethyl)-hexyl phthalate (MEHP), and mono-benzyl phthalate (MBzP) and leukocyte telomere length (LTL) in the adult population of the National Health and Nutrition Examination Survey (NHANES) 1999–2002 (n = 2472). After adjustment for potential confounders, participants in the 3rd and 4th quartiles of urinary MEHP had statistically significantly longer LTL (5.34%, 95% CI: 1.31, 9.53; and 7.14%, 95% CI: 2.94, 11.63; respectively) compared to the lowest quartile, with evidence of a dose–response relationship (p-trend = 0.01). The association remained when the analyses were stratified by age groups (20–39 years, 40–59 years, and 60 years and older), and sex. Furthermore, MBP and MBzP were associated with higher LTL in older participants. The age independent association between longer LTL and MEHP (a metabolite of DEHP) might suggest a possible role of MEHP as tumor promoter.