Evaluation of styrene oligomers eluted from polystyrene for estrogenicity in estrogen receptor binding assay, reporter gene assay, and uterotrophic assay

Ohno, Katsutoshi; Azuma, Yukimasa; Date, Katsuhiro; Nakano, Shigeru; Kobayashi, Toru; Nagao, Yasuhiro; Yamada, Toshihiro

doi:10.1016/s0278-6915(02)00211-9

Cited by 28 publications

(15 citation statements)

References 26 publications

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“…Based on concerns that styrene monomer and oligomers may leak from plastics used for food packing, in vitro and in vivo studies were conducted to evaluate such an endocrine action of styrene. While Kitamura et al (2003) demonstrated an endocrine effect of a metabolite of a styrene oligomer, other investigators have reported a lack of endocrine action (Date et al, 2002;Ohno et al, 2001Ohno et al, , 2003. The lack of endocrine-disrupting activity of styrene, applied via the relevant route (i.e., inhalation), is further corroborated by the unaffected prolactin and dopamine data of our previous study (Jarry et al, 2002) as well as by the hormone and neurotransmitter concentrations determined in the present experiment.…”

Section: Discussionsupporting

confidence: 84%

Effects of 5-Day Styrene Inhalation on Serum LH and Testosterone Levels and on Hypothalamic and Striatal Amino Acid Neurotransmitter Concentrations in Male Rats

Jarry¹,

Gamer²,

Wuttke³

2004

Inhalation Toxicology

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The volatile chemical styrene may impair male fertility. Testicular testosterone (T) production is controlled by the hypothalamic/pituitary/gonadal axis. From the mediobasal hypothalamus (MBH), gonadotropin-releasing hormone (GnRH) is released, which stimulates luteinizing hormone (LH) secretion from the pituitary, which in turn enhances T production. GnRH release is controlled by glutamate (GLU) and gamma-aminobutyric acid (GABA). GLU and GABA neurons are regulated by T. Thus, reduced fertility of styrene-exposed male workers may result from altered GLU/GABA neurotransmission, causing insufficient GnRH, LH, and T secretion. Therefore, we compared LH and T levels of male rats that have inhaled styrene (0, 150, 500, 1500 ppm for 6 h on 5 consecutive days) to GLU and GABA concentrations in the MBH and striatum. Animals were killed directly following the last exposure (immediate group) or after 24 h (recovery group). No suppression of LH or T levels was observed after styrene inhalation. LH levels of the immediate groups with 500 or 1500 ppm exposure were slightly but significantly elevated. Hypothalamic GLU and GABA concentrations remained unchanged. Increased striatal GABA concentrations were determined in recovery groups with 500 or 1500 ppm exposure. Striatal GLU concentrations remained unaffected. Thus, we demonstrate slightly increased LH and T levels in styrene-exposed male rats after inhalation of the two higher doses. This effect did not correlate with hypothalamic GLU and GABA concentrations. With the limitations inherent to any animal model, these data obtained from a 5-day exposure study with rats suggest, but do not unequivocally prove, that styrene may have also no reproductive toxicity effects in men chronically exposed to this chemical.

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Section: Discussionsupporting

confidence: 84%

Effects of 5-Day Styrene Inhalation on Serum LH and Testosterone Levels and on Hypothalamic and Striatal Amino Acid Neurotransmitter Concentrations in Male Rats

Jarry¹,

Gamer²,

Wuttke³

2004

Inhalation Toxicology

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“…An excess amount of the drug to be tested was added to pure water ( †Literature values. 4,5,[10][11][12][13][14][15][16][17][18][19] ‡Estimated values, the 10-logarithm of the octanol/water partition coefficient (logP) (www.syrres.com). §Calculated solubility using the Yalkowsky equation.…”

Section: Methodsmentioning

confidence: 99%

Determination of aqueous solubility by heating and equilibration: A technical note

Loftsson

Hreinsdóttir

2006

AAPS PharmSciTech

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A transmission near infrared (NIR) spectroscopic method has been developed for the nondestructive determination of drug content in tablets with less than 1% weight of active ingredient per weight of formulation (m/m) drug content. Tablets were manufactured with drug concentrations of approximately 0.5%, 0.7%, and 1.0% (m/m) and ranging in drug content from 0.71 to 2.51 mg per tablet. Transmission NIR spectra were obtained for 110 tablets that constituted the training set for the calibration model developed with partial least squares regression. The reference method for the calibration model was a validated UV spectrophotometric method. Several data preprocessing methods were used to reduce the effect of scattering on the NIR spectra and base the calibration model on spectral changes related to the drug concentration changes. The final calibration model included the spectral range from 11 216 to 8662 cm(-1), the standard normal variate (SNV), and first derivative spectral pretreatments. This model was used to predict an independent set of 48 tablets with a root mean standard error of prediction (RMSEP) of 0.14 mg, and a bias of only -0.05 mg per tablet. The study showed that transmission NIR spectroscopy is a viable alternative for nondestructive testing of low drug content tablets, available for the analysis of large numbers of tablets during process development and as a tool to detect drug agglomeration and evaluate process improvement efforts.

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“…Plastic articles made from PS are known to release styrene oligomers, which can bind to the estrogen receptor and exhibit estrogen-like activity (63,81). The potency and importance of this activity are subject to debate (80).…”

Section: Common Uses Of Polymers and Additivesmentioning

confidence: 99%

Plastics and Health Risks

Halden

2010

Annu. Rev. Public Health

726

363

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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 ...

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Evaluation of styrene oligomers eluted from polystyrene for estrogenicity in estrogen receptor binding assay, reporter gene assay, and uterotrophic assay

Cited by 28 publications

References 26 publications

Effects of 5-Day Styrene Inhalation on Serum LH and Testosterone Levels and on Hypothalamic and Striatal Amino Acid Neurotransmitter Concentrations in Male Rats

Effects of 5-Day Styrene Inhalation on Serum LH and Testosterone Levels and on Hypothalamic and Striatal Amino Acid Neurotransmitter Concentrations in Male Rats

Determination of aqueous solubility by heating and equilibration: A technical note

Plastics and Health Risks

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