Uterotrophic Assay of two Concentrations of Migrates from each of 23 Polystyrenes Administered Orally (by Gavage) to Immature Female Wistar Rats

Bachmann, Sabine; Hellwig, Järgen; Jäckh, Rudolf; Christian, Mildred S.

doi:10.3109/01480549809007402

Cited by 15 publications

(7 citation statements)

References 10 publications

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“…It has been reported that some styrene oligomers do not give a positive response in uterotrophic assay (Bachmann et al 1998;Fail et al 1998;Prinsen and Gouko 2001). However, the levels of active metabolites in the body would be an important factor determining the effects of the oligomers in vivo.…”

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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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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“…6-20 times the estimated maximum daily intake. 2,3 In the present experiment styrene trimer dose levels up to 1000 times the estimated maximum daily intake were examined. Groups of immature female rats, aged 18-20 days at the onset of treatment, were treated with extracts of GPPS with dose levels of styrene dimers of 6-60 g kg Ϫ1 body weight day…”

Section: Introductionmentioning

confidence: 99%

Determination of the oestrogenic (uterotrophic) activity of extracts of ‘general purpose polystyrene (GPPS)’ using immature female rats

Prinsen

Gouko

2001

J of Applied Toxicology

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In Japan there is growing concern about the possible adverse effects of consumption of food from styrene containers (mainly those made from polystyrene paper) due to the alleged oestrogenic activity of styrene oligomers (dimers and trimers), which may migrate into the food. To examine the possible oestrogenic activity of styrene dimers and trimers, extracts were made from 'general purpose polystyrene (GPPS)' and administered orally to immature female rats over a 4 day period. Increase of uterus weight (wet and blotted) was used for assessment of possible oestrogenic activity. To establish the sensitivity of the test method, immature rats were treated with diethylstilboestrol (DES), a well-known oestrogenic compound. It was found that treatment of rats with levels of up to 60 microg of styrene dimers and 930 microg of styrene trimers per kilogram body weight per day did not give any statistically significant increase of the uterus weight (wet or blotted), whereas DES caused statistically significant, dose-related increases in uterus weight at levels as low as 0.89 microg kg(-1) body weight day(-1). It was concluded that, compared with the estimated maximum human daily intake of styrene trimers of 1 microg kg(-1) body weight day(-1) from polystyrene food containers, the risk of adverse human health effects with respect to oestrogenicity may be considered negligible.

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“…(I) in compliance with Good Laboratory Practices (GLPS)~-~, (2) under third party supervision, and (3) without knowledge of the identity of the material processed. In addition to procedural information, this paper also supplies the rationales for dose selection and identified safety ratios.…”

Section: Introductionmentioning

confidence: 99%

Preparation and Analysis of Styrene Oligomers Containing Migrates from Various Polystyrenes Used in Food Packaging

Klärner¹,

Klenz²,

Eder³

et al. 1998

Drug and Chemical Toxicology

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An oligostyrene-like product (F2L5250) was reported to have estrogen-like activity (statistically significant increases in means for absolute uterine weight and the ratios of the uterine weight to terminal body weight) in juvenile female rats provided a dietary concentration of 100 ppm F2L5250 for four consecutive days. The highest no-effect-level (NOEL) for estrogenic activity was 80 ppm in the diet, corresponding to a daily intake of 13.3 mg F2L5250/kg. Although it is unlikely that such estrogenic tetramers would occur in commercial polystyrene, the Styrene Steering Committee (SSC) of the European Chemical Industry Council (CEFIC) sponsored the current extensive project to address any concern that human consumption of styrene oligomers migrating from polystyrene containers into food, e.g., from packaged yoghurt, or from the use of EPS coffee cups and related products, might affect human health. To ensure confidentiality and compliance with the highest scientific and regulatory standards, the entire project was conducted without knowledge of the oligomer migrates tested, and all activities were managed and audited under a contract between the SSC and a third party, Argus International. This paper describes the preparation and analyses of the 23 representative polystyrenes [9 general purpose polystyrenes (GPPS), 8 high impact polystyrenes (HIPS) and 6 expandable polystyrenes (EPS)] evaluated for estrogenicity in an in vivo uterotrophic assay in immature female rats. The polystyrene samples were chosen to represent food packaging applications. They were obtained from participating European Polystyrene Manufacturers, coded at the TNO Nutrition and Food Research Institute, Utrecht, The Netherlands (TNO) and sent to BASF, Ludwigshafen, Germany for preparation of test bars (GPPS and HIPS) or test foam parts (EPS). The prepared polystyrene test bars or test foam parts were submitted to elution with 50% aqueous (v/v) ethanol for 10 days at 40 degrees C, a procedure which simulates an exposure at ambient temperature for several weeks and represents an exaggeration in comparison with yogurt, for which directive 85/572/EEC1 defines 3% aqueous acetic acid as the official food simulant. To further exaggerate the potential concentration of the possible migrates, the surface/volume ratio selected for elution was the maximum experimentally possible, i.e., approximately 56 dm2/kg food for the GPPS and HIPS bars and approximately 38 dm2/kg food for the EPS foam, representing a multiple of approximately 9 (GPPS and HIPS) and 6 (EPS), times the conventional surface/volume ratio of 6 dm2/kg. These obtained styrene oligomer migrates were then diluted to 25% aqueous (v/v) ethanol, a concentration that could be tolerated by the test animals. After dilution, the low and high concentrations represented multiples of 0.5 and 4.6 (GPPS and HIPS) and 0.5 and 3.2 (EPS) the conventional surface/volume ratio, respectively. These levels simulated daily human consumption of 500 or 5,000 g of food for the GPPS and HIPS samples and of 500 or 3,150 ...

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Uterotrophic Assay of two Concentrations of Migrates from each of 23 Polystyrenes Administered Orally (by Gavage) to Immature Female Wistar Rats

Cited by 15 publications

References 10 publications

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

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

Determination of the oestrogenic (uterotrophic) activity of extracts of ‘general purpose polystyrene (GPPS)’ using immature female rats

Preparation and Analysis of Styrene Oligomers Containing Migrates from Various Polystyrenes Used in Food Packaging

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