title: Biological impact of phthalates.
abstract: Esters of phthalic acid are chemical agents used to improve the plasticity of industrial polymers. Their ubiquitous use in multiple commercial products results in extensive exposure to humans and the environment. This study investigated cytotoxicity, endocrine disruption, effects mediated via AhR, lipid peroxidation and effects on expression of enzymes of xenobiotic metabolism caused by di-(2-ethy hexyl) phthalate (DEHP), diethyl phthalate (DEP), dibutyl phthalate (DBP) and benzyl butyl phthalate (BBP) in developing fish embryos. Oxidative stress was identified as the critical mechanism of toxicity (CMTA) in the case of DEHP and DEP, while the efficient removal of DBP and BBP by phase 1 enzymes resulted in lesser toxicity. DEHP and DEP did not mimic estradiol (E(2)) in transactivation studies, but at concentrations of 10mg/L synthesis of sex steroid hormones was affected. Exposure to 10mg BBP/L resulted in weak transactivation of the estrogen receptor (ER). All phthalates exhibited weak potency as agonists of the aryl hydrocarbon receptor (AhR). The order of potency of the 4 phthalates studied was; DEHP>DEP>BBP>>DBP. The study highlights the need for simultaneous assessment of: (1) multiple cellular targets affected by phthalates and (2) phthalate mixtures to account for additive effects when multiple phthalates modulate the same pathway. Such cumulative assessment of multiple biological parameters is more realistic, and offers the possibility of more accurately identifying the CMTA.
authors.affiliation: Toxicology Center, University of Saskatchewan, Saskatoon, SK, Canada. mankidy@gmail.com
authors.forename: Rishikesh
authors.initials: R
authors.lastname: Mankidy
authors.forename: Steve
authors.initials: S
authors.lastname: Wiseman
authors.forename: Hong
authors.initials: H
authors.lastname: Ma
authors.forename: John P
authors.initials: JP
authors.lastname: Giesy
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D003530:Cyprinidae; D004477:Ectogenesis / Q000187:drug effects; D004625:Embryo, Nonmammalian / Q000187:drug effects* / Q000378:metabolism; D052244:Endocrine Disruptors / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D029941:Fish Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D050216:Metabolic Detoxication, Phase I; D018384:Oxidative Stress / Q000187:drug effects*; D010795:Phthalic Acids / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D010968:Plasticizers / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D052244:Endocrine Disruptors; D029941:Fish Proteins; D012739:Gonadal Steroid Hormones; D010795:Phthalic Acids; D010968:Plasticizers; D018336:Receptors, Aryl Hydrocarbon; D011960:Receptors, Estrogen