Endocrine Abstracts

Background: Phthalates are currently used in medical devices, adhesives as plasticizers. Masculine reproductive toxicity is the greatest concern associated with exposure, known as the “phthalate syndrome”. The European Chemicals Agency has recognized di-butyl-phthalate (DBP, CAS 84-74-2) as an endocrine disruptor with deleterious effects on reproductive hormones, with an estimated human intake of 0.84-5.22 μg/kg/day. Effects reported include the disruption of Sertoli and Leydig cells with decreased testicular production of androgens, known as the “testicular dysgenesis syndrome”. However, a quantitative relationship between DBP exposure and hormone levels is not available in the literature.

Objective: Review the scientific literature on DBP exposure measured as urinary metabolites, and corresponding reproductive hormone effects such as testosterone, in human adult men.

Methods: Four online scientific databases [PubMed, ISI Web of Science, Embase, Cochrane library] were searched in January 2022. The search criteria included English-language full text publications, human, adult men, serum testosterone total (TT) and testosterone free (fT) concentrations, urinary DBP metabolites concentrations (creatinine-adjusted values). Studies with n>100 participants were selected. Studies with a low score on qualitative assessment were excluded.

Results: Of the 329 search results, 11 toxicological studies met the inclusion criteria. Nine were cross-sectional studies conducted in East-Asia (4), Europe (4), North America (2), and Middle-East (1), and were conducted in the general population, occupational-exposed and fertility clinic population. The urinary DBP metabolites generally evaluated were mono-n-butyl-phthalate (MnBP) and mono-iso-butyl-phthalate (MiBP). The phthalates are often used in mixtures depending on the product specifications. Therefore, all the included studies provided urinary metabolites concentration of other phthalates. Phthalates may have a common metabolic pathway and consequently, the cumulative effect could alter the testosterone in serum but this was seldom discussed. All included studies used the same chemical analysis for quantifying urinary DBP metabolites (enzymatic hydrolysis, high-performance liquid chromatography with mass-spectrometry detection), while not all studies reported TT and fT. Preliminary results show that there is no significant correlation between urinary concentration of DBP metabolites and testosterone levels, although, several studies report a slight evidence for a reduction of TT and fT with increasing DBP exposure.

Conclusions: The review showed that the studies were incongruent and therefore, a significant correlation could not be established. However, the data suggest that adult men exposed to DBP are more likely to have altered testosterone levels. Future studies should explore possible relationships with luteinizing hormone, follicle-stimulating hormone, sex hormone binding globulin, estradiol and inhibin B in the current context.