Multiple Endocrine Disrupting Effects in Rats Perinatally Exposed to Butylparaben

Toxicol Sci. 2016 Jul;152(1):244-56. doi: 10.1093/toxsci/kfw079. Epub 2016 Apr 27.


Parabens comprise a group of preservatives commonly added to cosmetics, lotions, and other consumer products. Butylparaben has estrogenic and antiandrogenic properties and is known to reduce sperm counts in rats following perinatal exposure. Whether butylparaben exposure can affect other endocrine sensitive endpoints, however, remains largely unknown. In this study, time-mated Wistar rats (n = 18) were orally exposed to 0, 10, 100, or 500 mg/kg bw/d of butylparaben from gestation day 7 to pup day 22. Several endocrine-sensitive endpoints were adversely affected. In the 2 highest dose groups, the anogenital distance of newborn male and female offspring was significantly reduced, and in prepubertal females, ovary weights were reduced and mammary gland outgrowth was increased. In male offspring, sperm count was significantly reduced at all doses from 10 mg/kg bw/d. Testicular CYP19a1 (aromatase) expression was reduced in prepubertal, but not adult animals exposed to butylparaben. In adult testes, Nr5a1 expression was reduced at all doses, indicating persistent disruption of steroidogenesis. Prostate histology was altered at prepuberty and adult prostate weights were reduced in the high dose group. Thus, butylparaben exerted endocrine disrupting effects on both male and female offspring. The observed adverse developmental effect on sperm count at the lowest dose is highly relevant to risk assessment, as this is the lowest observed adverse effect level in a study on perinatal exposure to butylparaben.

Keywords: breast; endocrine disruption; paraben; prostate; reproduction; sexual development; testis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Aromatase / genetics
  • Aromatase / metabolism
  • Dose-Response Relationship, Drug
  • Endocrine Disruptors / toxicity*
  • Female
  • Gene Expression Regulation, Enzymologic / drug effects
  • Gestational Age
  • Male
  • Mammary Glands, Animal / drug effects
  • Mammary Glands, Animal / pathology
  • Maternal Exposure*
  • Ovary / drug effects
  • Ovary / pathology
  • Parabens / toxicity*
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Prostate / drug effects
  • Prostate / pathology
  • Rats, Wistar
  • Sperm Count
  • Steroidogenic Factor 1 / genetics
  • Steroidogenic Factor 1 / metabolism
  • Testis / drug effects
  • Testis / metabolism
  • Testis / pathology


  • Endocrine Disruptors
  • Parabens
  • Steroidogenic Factor 1
  • steroidogenic factor 1, rat
  • butylparaben
  • Aromatase