Biological Evaluation of Styrene Oligomers for Endocrine-Disrupting Effects

Nobuhara, Yoichi; Hirano, Seishiro; Azuma, Yukimasa; Date, Katsuhiro; Ohno, Katsutoshi; Tanaka, Kazunori; Matsushiro, Shoichiro; Sakurai, Takanobu; Shiozawa, Satoshi; Chiba, Masaru; Yamada, Toshihiro

doi:10.3358/shokueishi.40.36

Cited by 26 publications

(12 citation statements)

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“…These compounds might be endocrine disrupters. The effects of styrene trimers on uteri have not been found in in vivo studies using 21-day-old rats (10). However, fetuses are more vulnerable to estrogenic chemicals than are adults.…”

Section: Discussionmentioning

confidence: 97%

“…Azuma et al (11) and Nobuhara et al (10) reported that SD-1, SD-3, SD-4, ST-1, ST-2, ST-3, and ST-5 had no affinity for ER in an RI competitive binding assay. Although they examined the binding affinity of styrene oligomers at ≤ 10 -5 M for ER of rat uterus, we tested them at the concentrations up to 5 × 10 -3 or 5 × 10 -4 M for purified human ER α.…”

Section: Discussionmentioning

confidence: 99%

“…However, styrene oligomers were reported to have no endocrine disruptive effect both in a MCF-7 cell proliferation assay (10) and in a radioisotope (RI) receptor competitive-binding assay using rat estrogen receptor (10,11). Therefore, we tested 11 styrene oligomers including those found in food (4,5) in a proliferation assay at an optimal initial cell concentration using human breast tumor, highly estrogen-sensitive MCF-7 cells.…”

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confidence: 99%

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Certain styrene oligomers have proliferative activity on MCF-7 human breast tumor cells and binding affinity for human estrogen receptor.

Ohyama

Nagai²,

Tsuchiya³

2001

Environ Health Perspect

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Polystyrene used for food containers, such as takeout food containers, coffee cups, meat trays, soup bowls, and salad boxes (1), contains high levels of styrene dimers (90-1,030 µg/g) and styrene trimers (650-20,770 µg/g) as impurities (2,3). These styrene oligomers migrate from the polystyrene containers into the containers' contents (4-6). When polystyrene containers containing vegetable oil were treated by heating in a microwave oven or were incubated for 24 hr at 20°C, a styrene dimer, 2,4-diphenyl-1-butene (SD-2; 0-1.6 ng/cm 2 ) and styrene trimers 2,4,6-triphenyl-1-hexene (ST-1; 1.3-69.7 ng/cm 2 ), 1a-phenyl-4a-(1´-phenylethyl)tetralin (ST-2; 9.2-156 ng/cm 2 ), 1a-phenyl-4e-(1´-phenylethyl)tetralin (ST-3; 18.1-501 ng/cm 2 ), 1e-phenyl-4a-(1´-phenylethyl)tetralin (ST-4; 13.9-294 ng/cm 2 ), and 1e-phenyl-4e-(1´-phenylethyl)tetralin (ST-5; 18.7-306 ng/cm 2 ) migrated into the vegetable oil (4). When instant foods such as Chinese noodles, Japanese noodles, buckwheat noodles, chow mein, spaghetti, and rice were packed in polystyrene containers, styrene trimers ST-1 (0-8.1 µg/cup), ST-2 + ST-3 (0-13.8 µg/cup), ST-4 (0-5.2 µg/cup), and ST-5 (0-8.4 µg/cup) migrated (0-33.8 µg total styrene oligomers detected in a cup) from the containers into the foods after cooking in the cups, but the dimers did not (5). The maximum quantity of styrene trimers that migrated from containers to foods was higher than that of bisphenol A leached from the lacquer coating of vegetable cans (4-23 µg/can) (7).Colborn et al. (8) designated styrene dimers and trimers as endocrine disrupters in the Wingspread statement, and the Environmental Agency, Government of Japan, cited styrene dimers and trimers as compounds suspected of having endocrinedisruptive effects in its Strategic Programs on Environmental Endocrine Disrupters (9). However, styrene oligomers were reported to have no endocrine disruptive effect both in a MCF-7 cell proliferation assay (10) and in a radioisotope (RI) receptor competitive-binding assay using rat estrogen receptor (10,11). Therefore, we tested 11 styrene oligomers including those found in food (4,5) in a proliferation assay at an optimal initial cell concentration using human breast tumor, highly estrogen-sensitive MCF-7 cells. We also examined the binding potency of these styrene oligomers to human estrogen receptor α (hERα) in a non-RI receptor competitivebinding assay. Materials and MethodsChemicals. The styrene dimers 1,3-diphenyl propane (SD-1), SD-2, cis-1,2-diphenyl cyclobutane (SD-3), and trans-1,2-diphenyl cyclobutane (SD-4) and styrene trimers ST-1, ST-2, ST-3, ST-4, ST-5, 1e,3e,5a-triphenylcyclohexane (ST-6), and 1e,3e,5e-triphenylcyclohexane (ST-7) were purchased from Hayashi Pure Chemical Industry. (Osaka, Japan). The positive control, 17β-estradiol (E 2 ), was obtained from Calbiochem (Richmond, CA, USA). The chemical structures of these compounds are shown in Figure 1, and the purity of the compounds is summarized in Table 1.Solvent for styrene oligomers. Styrene oligomers and E 2 were dissolved ...

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Certain styrene oligomers have proliferative activity on MCF-7 human breast tumor cells and binding affinity for human estrogen receptor.

Ohyama

Nagai²,

Tsuchiya³

2001

Environ Health Perspect

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“…Nobuhara et al (1999) reported that styrene oligomers did not induce the proliferation of MCF-7 cells. We also showed in this study that these compounds do not exhibit estrogenic activity in the YES assay or estrogen screening assay using MCF-7 cells.…”

Section: Discussionmentioning

confidence: 99%

Estrogenic activity of styrene oligomers after metabolic activation by rat liver microsomes.

Kawa

Ohmegi

Sanoh

et al. 2003

Environ Health Perspect

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In this study we examined estrogenic activity of styrene oligomers after metabolic activation by rat liver microsomes. Trans-1,2-diphenylcyclobutane (TCB), cis-1,2-diphenylcyclobutane (CCB), 1,3-diphenylpropane, 2,4-diphenyl-1-butene, 2,4,6-triphenyl-1-hexene, and 1-alpha-phenyl-4ss-(1 -phenylethyl)tetralin were negative in the yeast estrogen screening assay and estrogen reporter assay using estrogen-responsive human breast cancer cell line MCF-7. However, TCB exhibited estrogenic activity after incubation with liver microsomes of phenobarbital-treated rats in the presence of reduced nicotinamide adenine dinucleotide phosphate (NADPH). Minor activity was observed when liver microsomes of untreated or 3-methylcholanthrene-treated rats were used instead of those from phenobarbital-treated rats. CCB, 1,3-diphenylpropane, and 2,4-diphenyl-1-butene also exhibited estrogenic activity after metabolic activation by liver microsomes, but the activity was lower than that of TCB. 2,4,6-Triphenyl-1-hexene and 1-alpha-phenyl-4ss-(1 -phenylethyl)tetralin did not show estrogenic activity after such incubation. When TCB was incubated with liver microsomes of phenobarbital-treated rats in the presence of NADPH, three metabolites were detected by high-performance liquid chromatography (HPLC). One metabolite isolated by HPLC exhibited a significant estrogenic activity. The active metabolite was identified as trans-1-(4-hydroxyphenyl)-2-phenylcyclobutane by mass and nuclear magnetic resonance spectral analysis. These results suggest that the estrogenic activity of TCB was caused by the formation of the 4-hydroxylated metabolite.

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“…The endocrine-disrupting potencies of SDs and STs were actively investigated in the late 1990s to early 2000s. Although there were some results indicating positive responses in in vitro tests [9] , the results based on many reliable studies including in vivo studies suggested that SDs and STs do not have endocrine disrupting potential [10] , [11] , [12] , [13] . For example, it was shown that SDs and STs extracted from polystyrene with acetone cause no reproductive toxicity in rats, either to dams or offspring, at concentrations of up to 1.0 mg/kg/day, which is a concentration 1000 times greater than the daily intake in humans [13] .…”

Section: Introductionmentioning

confidence: 99%

Genotoxicity of styrene oligomers extracted from polystyrene intended for use in contact with food

et al. 2014

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HighlightsWe evaluated the genotoxicity of styrene oligomers extracted from polystyrene intended for use in contact with food.Compared with 50% ethanol, acetone extracted a far greater amount of styrene dimers and trimers from polystyrene.Ames tests and an in vitro chromosomal aberration test were negative.The risk of the genotoxicity of styrene oligomers migrated from polystyrene food packaging into food is likely very low.

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Biological Evaluation of Styrene Oligomers for Endocrine-Disrupting Effects

Cited by 26 publications

References 1 publication

Certain styrene oligomers have proliferative activity on MCF-7 human breast tumor cells and binding affinity for human estrogen receptor.

Certain styrene oligomers have proliferative activity on MCF-7 human breast tumor cells and binding affinity for human estrogen receptor.

Estrogenic activity of styrene oligomers after metabolic activation by rat liver microsomes.

Genotoxicity of styrene oligomers extracted from polystyrene intended for use in contact with food

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