Lack of effect of butylparaben and methylparaben on the reproductive system in male rats.
BACKGROUND
Parabens are widely used preservatives in cosmetics and pharmaceutical products, and approved as food additives. Parabens have been considered safe for these uses for many years. Recently, adverse effects on male reproductive parameters in rats have been reported when parabens were given orally for 8 weeks starting at three weeks of age. Our studies used two representative parabens, methyl- and butylparaben, to try to replicate these studies and thereby evaluate potential reproductive effects in male Wistar rats.


METHODS
Diets containing 0, 100, 1000 or 10,000 ppm of either butyl- or methylparaben were fed to male rats for eight weeks. Rats were 22 days of age at the start of exposure. Parameters evaluated included organ weights, histopathology of reproductive tissues, sperm production, motility, morphology and reproductive hormone levels (butylparaben only).


RESULTS
None of the parameters evaluated for either paraben showed compound- or dosage-dependent adverse effects. Metabolism experiments of butylparaben indicate that it is rapidly metabolized by non-specific esterases to p-hydroxybenzoic acid and butanol, neither of which is estrogenic.


CONCLUSIONS
Exposure to methyl- or butylparaben in the diet for eight weeks did not affect any male reproductive organs or parameters at exposures as high as 10,000 ppm, corresponding to a mean daily dose of 1,141.1+/-58.9 or 1,087.6+/-67.8 mg/kg/day for methyl- and butylparaben, respectively. The rapid metabolism of parabens by esterases probably explains why these weakly estrogenic substances elicit no in vivo effects when administered by relevant exposure routes (i.e., topical and oral).
Hoberman
Alan M
AM
Charles River Preclinical Services, Horsham, PA 19044, USA. alan.hoberman@crl.com
Schreur
David K
DK
Leazer
Tyra
T
Daston
George P
GP
Carthew
Philip
P
Re
Thomas
T
Loretz
Linda
L
Mann
Peter
P
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005837:Genitalia, Male / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010226:Parabens / Q000493:pharmacokinetics / Q000494:pharmacology*; D011310:Preservatives, Pharmaceutical / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012867:Skin / Q000187:drug effects / Q000378:metabolism
D010226:Parabens; D011310:Preservatives, Pharmaceutical; C038091:butylparaben; C015358:methylparaben