NTP Center for the Evaluation of Risks to Human Reproduction: phthalates expert panel report on the reproductive and developmental toxicity of di-n-octyl phthalate

Kavlock, Robert J.; Boekelheide, Kim; Chapin, Robert E.; Cunningham, Michael L.; Faustman, Elaine M.; Foster, Paul M.D.; Golub, Mari S.; Henderson, Rogene F.; Hinberg, Irwin; Little, Ruth E.; Seed, Jennifer; Shea, Katherine M.; Tabacova, Sonia; Tyl, Rochelle W.; Williams, Paige L.; Zacharewski, Timothy R.

doi:10.1016/s0890-6238(02)00031-x

Cited by 76 publications

(38 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…And more and more researchers pay attention on DEHP. Studies about the threshold of DEHP had shown that 5 mg/kg/day was the no observed adverse effect level (NOAEL); 500 mg/kg/day DEHP levels can cause obvious toxicity in rats; 600 mg/kg was the threshold for the occurrence of acute toxicity in Wistar rat in the short term; and the LD50 of rats to DEHP was about 30 g/kg/day [22][23][24][25]. In order to better observe the toxic effects and mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Correction and Republication: Effect of Di-(2-ethylhexyl) phthalate on the hypothalamus-pituitary-thyroid axis in adolescent rat

et al. 2018

View full text Add to dashboard Cite

Abstract. Di-(2-ethylhexyl) phthalate (DEHP) is extensively used in many personal care and consumer products, which has resulted in widespread human exposure. Limited studies have suggested that exposure to DEHP may affect thyroid function, but little is known about the effect and mechanisms of DEHP exposure on the hypothalamic-pituitary-thyroid axis (HPTA). The present study was conducted to elucidate the potential mechanisms in which DEHP disrupts the function of the HPTA. Wistar rats were administered DEHP by gavage at 0, 5, 50, and 500 mg/kg/day for 28 days and then sacrificed within 24 h following the last dose. Hormones of HPTA was quantified with radioimmunoassay and enzyme-linked immunosorbent assay, protein levels of thyrotropin-releasing hormone receptor (TRHR) and thyroid-stimulating hormone receptor (TSHR) were analyzed by Western blot and immunohistochemistry, expression levels of TRHR and TSHR mRNA were measured by quantitative real-time PCR. Rats treated with DEHP resulted in increased bodyweight, on the HPTA, down-regulated the protein levels of TRH in the hypothalamus, up-regulated the protein and mRNA levels of TRHR in the pituitary, downregulated mRNA expression of TSHR in the thyroid, while the difference of TSH in various dose groups was not statistically significant and T3, T4, FT3, FT4 levels in serum were decreased compared with control. DEHP could interfere with the balance of HPTA of adolescent rats, and increase the body weight, down-regulate the homeostasis of thyroid related hormones and receptors expression levels. Correspondence to: Lin Ye, Department of Occupational and Environmental Health, School of Public Health, Jilin University, 1163 Xin Min Street, Changchun, 130021, China. E-mail: jlyelin@163.com *These authors equally contributed to this work. Abbreviations: DEHP, Di-(2-ethylhexyl) phthalate; EEDs, environmental endocrine disruptors; HPTA, hypothalamic-pituitary-thyroid axis; MEHP, mono-(2-ethylhexyl) phthalate; PAEs, Phthalic acid esters; PVC, polyvinyl chloride; QPCR, quantitative real-time PCR; THs, thyroid hormones; TRH, thyrotropin-releasing hormone; TRHR, thyrotropin-releasing hormone receptor; TSH, thyroidstimulating hormone; TSHR, thyroid-stimulating hormone receptor ambient air, water sources, and sediments [5][6][7]. Human exposure to PAEs mainly occurs through food due to the use of PVC in wrapping materials and food processing [1,8]. Once ingested through food contamination, di-(2-ethylhexyl) phthalate (DEHP), one of the most widely used and studied phthalates esters, is quickly metabolized to its monoester equivalent mono-(2-ethylhexyl) phthalate] (MEHP), which is preferentially absorbed [9,10]. The biological effects of MEHP are hence of major concern; however, gaining an understanding of the underlying mechanistic events has posed several challenges. In the past, researches about DEHP mainly focused on reproductive defects [11][12][13]. More recently, greater attention has been paid on the thyroid toxic of DEHP.The thyroid is the largest endocrine organ in h...

show abstract

Section: Discussionmentioning

confidence: 99%

Correction and Republication: Effect of Di-(2-ethylhexyl) phthalate on the hypothalamus-pituitary-thyroid axis in adolescent rat

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Important other additives include di-isononyl phthalate (DINP), dibutyl phthalate (DBP), butylbenzyl phthalate (BBP), di-isododecyl phthalate (DIDP), di-n-octyl phthalate (DnOP), and di-n-hexyl phthalate (DnHP) (55)(56)(57)(58)(59)(60)(61). Among the nonmedical applications of phthalate-containing plastics, usage in children's toys and baby care products stand out as being most controversial (20,91,92,99).…”

Section: Phthalatesmentioning

confidence: 99%

Plastics and Health Risks

Halden

2010

Annu. Rev. Public Health

705

363

View full text Add to dashboard Cite

By 2010, the worldwide annual production of plastics will surpass 300 million tons. Plastics are indispensable materials in modern society, and many products manufactured from plastics are a boon to public health (e.g., disposable syringes, intravenous bags). However, plastics also pose health risks. Of principal concern are endocrinedisrupting properties, as triggered for example by bisphenol A and di-(2-ethylhexyl) phthalate (DEHP). Opinions on the safety of plastics vary widely, and despite more than five decades of research, scientific consensus on product safety is still elusive. This literature review summarizes information from more than 120 peer-reviewed publications on health effects of plastics and plasticizers in lab animals and humans. It examines problematic exposures of susceptible populations and also briefly summarizes adverse environmental impacts from plastic pollution. Ongoing efforts to steer human society toward resource conservation and sustainable consumption are discussed, including the concept of the 5 Rs-i.e., reduce, reuse, recycle, rethink, restrain-for minimizing preand postnatal exposures to potentially harmful components of plastics. BRIEF HISTORY OF PLASTICSPlastics are ubiquitous in modern life. Early uses date back to 1600 b.c. when natural rubber was shaped by human hands and polymerized into objects of utility in prehistoric mesoamerica (46). The exploitation of plastics was jumpstarted in 1839 with the discovery of vulcanized rubber and polystyrene (PS) (3). The first truly synthetic polymer, Bakelite, was produced in Belgium in 1907 (110). Mass production of plastics began in the 1940s and has continued to expand ever since. There are now 20 different groups of plastics, whose worldwide Plastics can be divided into two major categories: thermosets and thermoplastics. A thermoset is a polymer that solidifies or "sets" irreversibly when heated. They are useful for their durability and strength, and are therefore used primarily in automobiles and construction applications. Other uses are adhesives, inks, and coatings. PLASTICS/POLYMERSA thermoplastic is a polymer in which the molecules are held together by weak bonds, creating plastics that soften when exposed to heat and return to original condition at room temperature. Thermoplastics can easily be shaped and molded into products such as milk jugs, floor coverings, credit cards, and carpet fibers.Plastic resins are processed in several ways, including extrusion, injection molding, blow molding, and rotational molding. All of these processes involve using heat and/or pressure to form plastic resin into useful products, such as containers or plastic film. (Reproduced from U.S. EPA, http://www.epa.gov/waste/ conserve/materials/plastics.htm) (113) usage was on the order of 245 million tons for the year 2006 (6). Annual world production will likely have surpassed the 300-million-ton mark by the time this article appears in print. The U.S. Environmental Protection Agency's definition of plastics and polymers is shown in ...

show abstract

“…These esters have been shown to produce a syndrome of reproductive abnormalities -the phthalate syndrome, characterized by malformations of the epididymis, vas deferens, seminal vesicles, prostate, external genitalia (hypospadias), cryptorchidism [10]. On other hand, only a limited number of studies in human populations suggest an association between phthalate exposure and adverse reproductive health outcomes [35]. A correlation was found between urinary phthalate levels and pregnancy complications such as anemia, toxemia, and preeclampsia in women living near a plastics manufacturer [36,37].…”

Section: Reproductive Hormones and Cryptorchidismmentioning

confidence: 99%

Exposure to phthalates: Reproductive outcome and children health. A review of epidemiological studies

Jurewicz

Hanke

2011

International Journal of Occupational Medicine and Environmental Health

256

139

View full text Add to dashboard Cite

Phthalates are a family of industrial chemicals that have been used for a variety of purposes. As the potential consequences of human exposure to phthalates have raised concerns in the general population, they have been studied in susceptible subjects such as pregnant women, infants and children. This article aims at evaluating the impact of exposure to phthalates on reproductive outcomes and children health by reviewing most recent published literature. Epidemiological studies focusing on exposure to phthalates and pregnancy outcome, genital development, semen quality, precocious puberty, thyroid function, respiratory symptoms and neurodevelopment in children for the last ten years were identified by a search of the PubMed, Medline, Ebsco, Agricola and Toxnet literature bases. The results from the presented studies suggest that there are strong and rather consistent indications that phthalates increase the risk of allergy and asthma and have an adverse impact on children's neurodevelopment reflected by quality of alertness among girls, decreased (less masculine) composite score in boys and attention deficit hyperactivity disorder. Results of few studies demonstrate negative associations between phthalate levels commonly experienced by the public and impaired sperm quality (concentration, morphology, motility). Phthalates negatively impact also on gestational age and head circumference; however, the results of the studies were not consistent. In all the reviewed studies, exposure to phthalates adversely affected the level of reproductive hormones (luteinizing hormone, free testosterone, sex hormone-binding globulin), anogenital distance and thyroid function. The urinary le vels of phthalates were significantly higher in the pubertal gynecomastia group, in serum in girls with premature thelarche and in girls with precocious puberty. Epidemiological studies, in spite of their limitations, suggest that phthalates may affect reproductive outcome and children health. Considering the suggested health effects, more epidemiologic data is urgently needed and, in the meantime, precautionary policies must be implemented.

show abstract

NTP Center for the Evaluation of Risks to Human Reproduction: phthalates expert panel report on the reproductive and developmental toxicity of di-n-octyl phthalate

Cited by 76 publications

References 22 publications

Correction and Republication: Effect of Di-(2-ethylhexyl) phthalate on the hypothalamus-pituitary-thyroid axis in adolescent rat

Correction and Republication: Effect of Di-(2-ethylhexyl) phthalate on the hypothalamus-pituitary-thyroid axis in adolescent rat

Plastics and Health Risks

Exposure to phthalates: Reproductive outcome and children health. A review of epidemiological studies

Contact Info

Product

Resources

About