Multiple Endocrine Disrupting Effects in Rats Perinatally Exposed to Butylparaben.
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.
National Food Institute, Technical University of Denmark, Søborg, Denmark jubo@food.dtu.dk.
J
J
Boberg
National Food Institute, Technical University of Denmark, Søborg, Denmark.
M
M
Axelstad
National Food Institute, Technical University of Denmark, Søborg, Denmark.
T
T
Svingen
National Food Institute, Technical University of Denmark, Søborg, Denmark.
K
K
Mandrup
National Food Institute, Technical University of Denmark, Søborg, Denmark.
S
S
Christiansen
National Food Institute, Technical University of Denmark, Søborg, Denmark.
A M
AM
Vinggaard
National Food Institute, Technical University of Denmark, Søborg, Denmark.
U
U
Hass
D000818:Animals; D000831:Animals, Newborn; D001141:Aromatase / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000633:toxicity*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005865:Gestational Age; D008297:Male; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000473:pathology; D018811:Maternal Exposure; D010053:Ovary / Q000187:drug effects / Q000473:pathology; D010226:Parabens / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011467:Prostate / Q000187:drug effects / Q000473:pathology; D017208:Rats, Wistar; D013076:Sperm Count; D054339:Steroidogenic Factor 1 / Q000235:genetics / Q000378:metabolism; D013737:Testis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D052244:Endocrine Disruptors; D010226:Parabens; D054339:Steroidogenic Factor 1; C515060:steroidogenic factor 1, rat; C038091:butylparaben; D001141:Aromatase
breast; endocrine disruption; paraben; prostate; reproduction; sexual development; testis