Systematic review and quality ranking of studies of two phthalate metabolites and anogenital distance, bone health, inflammation, and oxidative stress

Abstract

Phthalates are ubiquitous chemical compounds, and two-di-ethyl phthalate (DEP) and di-isobutyl phthalate (DiBP)-are not currently regulated by the U.S. Congress or the European Union. While many reviews of phthalates have been published, none have examined bone health, inflammation, or oxidative stress; anogenital distance was most recently reviewed in 2014. The objective of this paper is to determine if an association exists between mono-ethyl phthalate (MEP) or mono-isobutyl phthalate (MiBP), metabolites of DEP and DiBP, respectively, and the four outcomes indicated above. We conducted a literature search of PubMed through December 2017 and included 29 observational epidemiologic studies published in English that assessed MEP and/or MiBP in relation to one of the above four health outcomes in humans. Two authors rated each paper using a modified Downs and Black (DB) assessment tool; a third author settled score disagreements. A single author extracted information related to the study population, exposure and outcome assessment, covariates, and significant results from each article. Ten studies were identified on anogenital distance, four on bone health, five on inflammation, and thirteen on oxidative stress. Score percentages (total points given out of total possible points) were calculated for each study. The current research suggests a positive association between MiBP and two measures of oxidative stress, 8-hydroxydeoxyguanosine (8-OHdG) and 8-isoprostane. MEP is potentially associated with 8-OHdG as well, although the evidence is limited by fewer highquality studies. There does not appear to be an association between anogenital distance and MEP or MiBP, and it is unclear if relationships exist between these phthalate metabolites and bone health and inflammation. Given the role that oxidative stress plays in a number of diseases and the ubiquity of MEP and MiBP, it is important that individuals be aware of potential sources of exposure to these chemicals.

Di‐(2‐ethylhexyl) phthalate exposure links to inflammation and low bone mass in premenopausal and postmenopausal females: Evidence from ovariectomized mice and humans

“…Phthalate exposure induces osteoporosis through a variety of mechanisms, including estrogen-disruption, PPARγ stimulation, oxidative stress, and inflammation pathways. 15,22,26 30 DEHP exposure also upregulates the gene expressions of IL-8 and IL-10 by zebrafish intestines. 31 Furthermore, a variety of inflammatory cytokines, including plasma IL-6, IL-17A, and tissue TNFα have been shown to be upregulated by DEHP stimulation during the juvenile period in a mouse model through epigenetic regulation.…”

“…Phthalate exposure induces osteoporosis through a variety of mechanisms, including estrogen‐disruption, PPARγ stimulation, oxidative stress, and inflammation pathways 15,22,26 . In addition, increased serum C‐reactive protein secondary to DiBP and BBP exposures have been clearly demonstrated in a large‐scale population‐based study 27 .…”

“…Although associations between phthalate exposure and the risk of low bone mineral density (BMD) or osteoporosis in postmenopausal women have been found in recent studies, 12–14 the impact of long‐term phthalate exposure on bone health among younger women remains unknown. Phthalates are well‐known estrogen disruptors and inducers of oxidative stress and inflammation 15,16 . Nevertheless, the role of inflammation related to phthalate exposure on bone health in women has not been fully elucidated to date.…”

“…Phthalates are well-known estrogen disruptors and inducers of oxidative stress and inflammation. 15,16 Nevertheless, the role of inflammation related to phthalate exposure on bone health in women has not been fully elucidated to date.…”

Endocrine Disruptors as a New Etiologic Factor of Bone Tissue Diseases (Review)

“…The experimental studies have shown that the main mechanism of osteoporosis under the condition of estrogenic deprivation is the PEs-induced reduction of osteocalcin production [ 99 ]. Impaired synthesis of vitamin D is considered as a second pathogenetic link in the development of osteoporosis caused by PEs exposure, however, information on this problem is controversial [ 47 , 100 , 101 ].…”