# Plaaben Compounds--Part I: An Overview of Their Characteristics, Detection, and Impacts
## 3 Paraben Potential Impacts
### Impacts in Animals
The authors found out that the metabolite did not show estrogenic activity, while all the parabens showed estrogenic activity for a dose 100-300 mg/kg/day [19]. [PERSON] et al. [90] tested the effect of propylparaben at doses of 0%, 0.01%, 0.10% and 1% in 3-week-old rats and, after 4 weeks, their epididymides, prostates, seminal vesicles and preputial plans were analyzed. The weight of the organs was not affected, but a decrease in concentration and reserve of sperm was noticed with an increase in PP dose; this difference was significant at 0.10% or higher doses. For all groups, daily sperm production and its efficiency decreased significantly, and, serum testosterone also decreased, with special significance for the group that received the higher dose of PP. The exposure level for the observed effects is the same as the acceptable upper limit as daily intake (10 mg/kg body weight/day) of parabens in the EU and in Japan. [PERSON] et al. [91] performed experiments using benzylparaben in Sprague-Dawley (SD) rats using intragastric administration. The authors found that a dose of 0.16 mg/kg body weight or higher provokes an increase in uterine weight of rats, and these results were also supported by their tests in a human estrogen receptor \(\alpha\) (hER\(\alpha\))-coactivator recruiting assay and in silico molecular docking analysis, which sowed estrogenic activity for BeP for concentrations of 1 \(\times\) 10\({}^{-8}\) M or higher. [PERSON] et al. [92] verified a progressive detachment and sloughing of spermatogenic cells into the lumen of the seminiferous tubules by the administration of 1000 mg/kg of butylparaben in three-week-old male rats, and the apoptosis of spermatogenic cells was higher compared to the control group, leading the authors to think that BuP can also induce the apoptosis of the spermatogenic cells. However, [PERSON] et al. [93] tested an exposition of 0, 5000, 15,000 and 40,000 ppm of BuP in Sprague-Dawley rats and did not find evidence of alterations in fertility, fecundity, pubertal attainment, or reproductive parameters in F0, F1 and F2 generations, but the authors verified that BuP caused an increase in liver weight and liver lesions which let the authors to think that the target organ of BuP is the liver. [PERSON] et al. [94] tested the effect of isopropylparaben and isobutylparaben for dermal toxicity in 28 days, for doses of 50, 100, 300 or 600 mg/kg body weight/day of rats, concluding that there were no significant changes in body or organs, but these parabens caused skin damage in female rats. Additionally, the analysis of six serum hormones showed that only FSH decreased in the mixture of parabens at dose of 100 mg/kg body weight/day or higher. [PERSON] et al. [95] tested the presence of n-butylparaben in F0 female rats by subcutaneous application with doses of 10, 100 and 1000 mg/kg body weight/day in corn oil, from gestation (day 6) until postnatal day (day 21), and the F1 rats were analyzed at postnatal days 30, 45 and 75. The authors verified the delayed age of vaginal openings with disturbed estrus cycle in F1 female rats, reduction in fertility, problems in spermatogenesis, decrease in estradiol and progesterone, increase in testosterone levels, problems in folliciculogenesis with increase in the number of primordial follicle maturation and reduced number of copora lautea, degenerated follicles in the ovaries, problems in the development of the myometrium in the uteruses of female rats and problems in levels of several estrogenic receptors. Additionally, [PERSON] et al. [96] tested the effect of methyl-, ethyl-, propyl-, isopropyl-, butyl- and isobutylparaben in female Sprague-Dawley rats during the ingestion of 62.5, 250 and 1000 mg/kg body weight/day from postnatal day 21 to day 40. The authors concluded that 1000 mg/kg body weight/day of MP and iso-PP delayed vaginal opening and decreased the length of the estrous cycle, and verified the weight increase in ovaries, adrenal glands, thyroid glands, liver, and kidneys.