# Plaaben Compounds--Part I: An Overview of Their Characteristics, Detection, and Impacts
## 3 Paraben Potential Impacts
### Impacts in Animals
However, and although the conclusion of the test was that MP was not carcinogenic, some experiments in rats allowed an incidence of 1.5% for injection-site tumors (fibrosarcoma) compared to control [21; 80]. For other studies, in tumors that appeared in rats treated with MP, only mammary fibroadenoma was higher than negative controls (8% and 1%, respectively), and the incidence of injection-site tumors, pituitary adenomas, uterine polyps and leukemias did not had a different incidence compared to controls [21; 80]. However, in general, the studies concluded that methylparaben is not carcinogenic for rats and mice, and for other studies in rats, mice, hamsters, and rabbits it was concluded that MP is not embryotoxic or teratogenic [21; 81; 82]. [PERSON] et al. [38] tested 10% solutions of MP and PP in rabbits and no irritation was observed in skin, but undiluted MP was tested, and 0.1 mL sample of ingredient caused mild irritation, and products containing 0.2-0.8% of the products showed mild or no irritation whereas a product of 0.2% MP and 0.1% PP showed a minimal irritation in rabbits [21]. Additionally, a hairdressing product with 0.2% of MP was also tested in rabbits for 21 days, and 24 h after each application the skin sites showed the presence of erythema and edema. In the beginning, the material produced light irritation but at the end of the first week this evolved to mild and moderate irritations [21, 37]. [PERSON] et al. [83], [PERSON] [84] and [PERSON] [37] tested MP products for evidence of eye irritation. The first authors did not find evidence of eye irritation for 0.1-0.2% MP solution, the second showed that solutions of 0.2% provoked slight conjunctival hyperemia, and the third showed that the product caused slight transient irritation [21]. For rats, [PERSON] et al. [85] tested daily use of 0.05% MP for 1 month and concluded that the rats that underwent MP treatments showed corneal and conjunctival damage, including an increase in the epithelial cell layers, the loss of goblet cells, appearance of keratinization of the most superficial cells, increase in limbal stroma and increase in the immune cell infiltration [21]. Other studies using MP, EP, PP and/or BuP at concentrations of 0.1-0.8% did not show evidence of eye irritation for most products, but some of them produced slight or minimal eye irritation [21, 37]. [PERSON] et al. [86] tested the effect of oral administration of EP in rats at doses of 0.2%, 1% and 2% for 25 weeks. The only difference observed was that in male rats fed with 0.2% EP, body weight increased in comparation to control group, while for 1% and 2%, the male rats showed a decrease in body weight [19]. [PERSON] et al. [87] tested the effect of iso-butylparaben at doses of 0%, 0.6%, 1.25%, 2.5%, 5% and 10% for 6 weeks. The mice fed with the 5% and 10% doses died in the first 2 weeks, and a decrease of about 10% was noted in mice fed with the paraben at 1.25% and 2.5%. No significant lesions were found in rats fed with 0.6% of iso-butylparaben, but for mice fed with 1.25% or higher dose, the existence of atrophy of the spleen, thymus and lymph nodes, multifocal degeneration, and necrosis of the hepatic parenchyma was noted [19]. [PERSON] et al. [88] proved the estrogenic behaviors of MP, EP and PP, and BuP and p-hydroxybenzoic acid in a mouse uterotrophic assay of Immature B6D2F1 mice and after 4 days of oral or subcutaneous administration of parabens, an increase in uterus weight was observed. However, up to 100 mg/kg/day, none of the tested parabens caused estrogenic activity, even for 1000 mg/kg/day for ethylparaben [19]. The same was observed by [PERSON] et al. [43], where the subcutaneous administration of iso-butylparaben increased the uterine weight of immature mice after three doses of 1.2 or 12 mg of parabens. [PERSON] et al. [89] tested the estrogenic activity of EP, PP and BuP and their common metabolite p-hydroxybenzoic acid in sexually immature rainbow trout.