Uterotrophic assay of two concentrations of migrates from each of 23 polystyrenes administered orally (by gavage) to immature female Wistar rats.

The Styrene Steering Committee (SSC) of the European Chemical Industry Council (CEFIC) sponsored this work to address any concern that styrene dimers and trimers that might migrate from polystyrene containers into food could possess some estrogenic activity and thus possibly affect human health. All phases of the study were conducted in conformance with GLP regulations and without knowledge of the oligomer migrates tested. All activities were managed and audited under a third-party contract between the SSC and Argus International. Low and high doses of the styrene oligomer migrates of 23 polystyrene samples [i.e. 9 general purpose polystyrenes (GPPS), 8 high impact polystyrenes (HIPS) and 6 expandable polystyrenes (EPS)] were tested for estrogenicity in an in vivo uterotrophic assay (immature female rat model). This model is considered to be the "gold standard" for use in screening for estrogenic effects because it evaluates both direct and indirect potential effects. The two concentrations of migrates of each of the 23 polystyrenes tested were selected to simulate daily human consumption of a low and high amount of food. Representative dimer and trimer concentrations were obtained in conformance with EEC Council Directives and calculated to be at levels simulating human consumption of 0.5 or 5 kg of food for the GPPS and the HIPS samples and of 0.5 or 3.15 kg of food for the EPS samples, respectively. The study was conducted in a series of three blocks. Each block included concurrent untreated control (negative control), vehicle control (25% ethanol, 20 ml/kg/day) and positive control (diethylstilbestrol-dipropionate, DES-DP, 5 micrograms/kg/day) groups, and low and high doses of each of 7 (1 block) or 8 (2 blocks) polystyrene oligomer migrates. Each group in each block consisted of 10 immature Wistar (Chbb: THOM-SPF) female rats. Beginning when the rats were 22 +/- 1 days of age, each rat was appropriately handled (untreated control group) or administered twice daily oral (gavage) dosages of the vehicle, positive control agent or one of the two doses of the migrates of each polystyrene for 4 consecutive days and then sacrificed at 26 +/- 1 days of age. The uterus of each rat was weighed, and the uterine weight was compared with the terminal body weight. The positive control agent (DES-DP, 5 micrograms/kg/day) significantly increased both absolute and relative (to terminal body weight) uterine weights, as compared to the untreated and vehicle control group values in each block, demonstrating sensitivity and response of the animals to an estrogenic agent. None of the 23 polystyrene oligomer migrates tested at low and high doses demonstrated biologically important or statistically significant differences from the untreated or vehicle control group values for absolute or relative (to body weight) uterine weights. Based on these data, it is concluded that low and high doses of the 23 polystyrene oligomer migrates tested did not induce an estrogenic response.