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Propylparaben was investigated for estrogenic activity in several in vitro and in vivo studies. In estrogen receptor (ER) competitive binding assays using the human MCF-7 breast cancer cell line and isolated ER from rat uteri, propylparaben showed a weak ER binding affinity with IC50 values of 1.65 - 245 µM (Okubo et al., 2001; Byford et al., 2002; Blair et al., 2000; Vo et al., 2010). In comparison, for 17β-estradiol an IC50 value of 0.0009 µM was determined (Blair et al., 2000). 

For cell proliferation in MCF-7 cells, an EC50 value of 1.9 µM propylparaben was determined (Okubo et al., 2001). In comparison, for 17β-estradiol, an EC50 value of 0.0000016 µM was determined for cell proliferation.

Uterotrophic assays according to OECD 440 were conducted in rats and mice. Immature rats were treated subcutaneously with 6.5-195 mg/kg bw/d propylparaben for 3 consecutive days (Lemini et al., 2003). Significantly increased uterine weights (wet and dry) were noted at propylparaben doses of 65 and 195 mg/kg bw/d. In the same study, immature and adult ovariectomised mice were treated subcutaneously with up to 195 mg/kg bw/d for 3 consecutive days. Uterine weights in immature and ovariectomised mice increased from in all dose groups and were statistically significant at 20, 65 and 195 mg/kg bw/d. Histopathological examination of uterine horns of treated ovariectomised mice resulted in significantly increased luminal epithelium height, glandular epithelium height and myometrium width at doses of 65 and 195 mg/kg bw/d. No lower doses were tested for histopathological abnormalities.

In a further uterotrophic assay according to OECD 440, 18-20 d old mice were orally treated with 100 mg/kg bw/d propylparaben for 3 consecutive days (Hossaini et al., 2000). Propylparaben did not influence the uterus wet weight and the uterine weight to body weight ratio after repeated oral doses of 100 mg/kg bw/d.

In a further study conducted by Vo et al. (2010) to investigate the estrogenic potential of propylparaben, no significant effects on vaginal opening day, estrous cycle as well as body weight and uterus, pituitary, ovary, thyroid, kidney and liver weights of peripubertal rats treated by gavage with 62.5-1000 mg/kg bw/d propylparaben for 20 d were observed. In the 1000 mg/kg bw/d group, the adrenal gland weight was statistically significantly but not biologically relevant increased. Histopathological changes were observed in the uteri of the high dose group. The uteri showed some effects in the muscle layers, including myometrial hypertrophy. Furthermore, the uterus thickness was significantly increased in the high dose group. A decrease of corpora lutea was observed in 3 (30%), 2 (20%) and 3 (30%) animals of the 62.5, 250 and 1000 mg/kg bw/d groups. No decrease of corpora lutea was observed in any animal of the negative control. No dose-related effects on estradiol, prolactin and tetra-iodothyronine (T4) level were noticed in serum of the treatment groups. The tetra-iodothyronine (T4) level was statistically significant reduced in the mid dose group.

In conclusion, in several ER competitive binding assays, propylparaben was shown to have a weak binding affinity (Okubo et al., 2001; Byford et al., 2002; Blair et al., 2000; Vo et al., 2010). No effects of propylparaben were observed on vaginal opening day, estrous cycle, body and organ weights of peripubertal rats (Vo et al., 2010). However, in uterotrophic assays effects were observed in immature rats and immature and ovarictomized mice at subcutaneous propylparaben doses starting from 20 mg/kg bw/d for 3 consecutive days (Lemini et al., 2003) and in peripubertal rats at propylparaben doses starting from 1000 mg/kg bw/d for 20 d by gavage (Vo et al., 2010). In a further uterotrophic assay in immature mice propylparaben did not influence the uterus wet weight and the uterine weight to body weight ratio after repeated oral doses of 100 mg/kg bw/d (Hossaini et al., 2000).