Morphometric analysis of mice uteri treated with the preservatives methyl, ethyl, propyl, and butylparaben.
The alkyl esters of p-hydroxybenzoic acid (PHBA) known as parabens (Pbens) are widely used as preservatives in food, pharmaceuticals, and cosmetics. Several in vivo and in vitro studies have shown these compounds to be estrogenic. Here, for the first time, we present evidence of their estrogenicity using a morphometric analysis of uteri from mice treated with the preservatives methylparaben (MePben), ethylparaben (EtPben), propylparaben (PrPben), and butylparaben (BuPben) compared with estradiol (E2). Different groups of adult ovariectomized (Ovx) CD1 mice were subcutaneously (sc) treated daily for three days with two different equimolar doses (362 and 1086 micromol/kg) of the Pbens: MePben (55 and 165 mg/kg), EtPben (60 and 180 mg/kg), PrPben (65 and 195 mg/kg), BuPben (70 and 210 mg/kg), E2 (10 microg/kg; 0.036 micromol/kg), and vehicle (propyleneglycol; V, 10 mL/kg). On the fourth day, uteri were dissected, blotted, weighed, and placed in a fixative solution for 24 h. The paraffin embeded uteri were cut to obtain 7 microm thick transversal sections. Luminal epithelium heights (LEH), glandular epithelium heights (GEH), and myometrium widths (MW) were measured. The highest Pbens dose was able to produce uterotrophic effects (38 to 76%) compared to E2 efects (100%). The relative uterotrophic potency to E2 (100) was from 0.02 to 0.009. Significant increases (P < 0.05) in LEH, GEH, and MW as compared with V were obtained: LEH from 87 to 113% (E2 153%), GEH from 10 to 40% (E2 60%), and MW from 35 to 43% (E2 88%). These results confirm that Pbens at the doses assayed here induce estrogenic histological changes in the uteri of Ovx mice.
Lemini
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C
Departamento de Farmacología, Facultad de Medicina, UNAM, Ciudad Universitaria, Mexico. clemini@servidor.unam.mx
Hernández
A
A
Jaimez
R
R
Franco
Y
Y
Avila
M E
ME
Castell
A
A
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000009:adverse effects*; D005260:Female; D005520:Food Preservatives / Q000009:adverse effects*; D051379:Mice; D010052:Ovariectomy; D010226:Parabens / Q000009:adverse effects*; D011310:Preservatives, Pharmaceutical / Q000009:adverse effects*; D014599:Uterus / Q000187:drug effects* / Q000473:pathology
D004967:Estrogens; D005520:Food Preservatives; D010226:Parabens; D011310:Preservatives, Pharmaceutical; C012313:ethyl-p-hydroxybenzoate; C038091:butylparaben; C015358:methylparaben; C006068:propylparaben