Oral propylparaben administration to juvenile male Wistar rats did not induce toxicity in reproductive organs. 2013

Vincent Gazin, and Edward Marsden, and Fabien Marguerite
* French Medecines Agency Afssaps, 93285 Saint Denis Cedex, Paris, France.

Parabens are in widespread use as preservatives in drugs. In the late 1990 s, concerns were raised about their capacity to disrupt endocrine function based on in vitro data and in vivo uterotrophic tests. Studies in juvenile male rats provided conflicting results on pospubertal sperm production. In an exploratory pharmacokinetic study, Wistar male rats received a single dose of propylparaben (PP) at 3, 10, 100, or 1000 mg/kg, orally on postnatal day (PND) 31. Plasma PP concentrations were quantifiable up 8h after dosing with a mean T max value of 15 min. Distribution was 4.8 l/kg, the plasma elimination half-life was 47 min, and clearance was 4.20 (l/h)/kg at 10mg/kg. A sulfoconjugated metabolite was detected. In the juvenile toxicology study, PP was orally administered by gavage to 20 Wistar male rats at doses of 3, 10, 100, or 1000 mg/kg/day in 1% hydroxyethylcellulose for 8 weeks starting on PND21. A first subgroup of 10 males/dose was necropsied immediately after the 8-week exposure period; a second subgroup of 10 males/dose was necropsied after a 26-week washout period. Blood samples were taken from additional satellite animals after dosing on PND21 and PND77 for toxicokinetic analysis. There was no evidence of an effect of PP on the weight of the male reproductive organs, epididymal sperm parameters, hormone levels, or histopathology. The dose of 1000 mg/kg/day was the no-observed adverse effect level, corresponding to a maximum plasma concentration of 12,030 ng/ml and exposure to 47 760 ng ยท h/ml (AUC0-8 h) at the end of the treatment.

UI MeSH Term Description Entries
D008297 Male Males
D009929 Organ Size The measurement of an organ in volume, mass, or heaviness. Organ Volume,Organ Weight,Size, Organ,Weight, Organ
D010226 Parabens Methyl, propyl, butyl, and ethyl esters of p-hydroxybenzoic acid. They have been approved by the FDA as antimicrobial agents for foods and pharmaceuticals. (From Hawley's Condensed Chemical Dictionary, 11th ed, p872) 4-Hydroxybenzoic Acids,Paraben,para-Hydroxybenzoic Acids,4 Hydroxybenzoic Acids,para Hydroxybenzoic Acids
D002853 Chromatography, Liquid Chromatographic techniques in which the mobile phase is a liquid. Liquid Chromatography
D005837 Genitalia, Male The male reproductive organs. They are divided into the external organs (PENIS; SCROTUM; and URETHRA) and the internal organs (TESTIS; EPIDIDYMIS; VAS DEFERENS; SEMINAL VESICLES; EJACULATORY DUCTS; PROSTATE; and BULBOURETHRAL GLANDS). Accessory Sex Organs, Male,Genital Organs, Male,Sex Organs, Accessory, Male,Genitals, Male,Reproductive System, Male,Genital, Male,Male Genital,Male Genital Organs,Male Genitalia,Male Genitals,Male Reproductive System,Male Reproductive Systems,Reproductive Systems, Male
D006207 Half-Life The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. Halflife,Half Life,Half-Lifes,Halflifes
D000284 Administration, Oral The giving of drugs, chemicals, or other substances by mouth. Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012741 Sexual Maturation Achievement of full sexual capacity in animals and in humans. Sex Maturation,Maturation, Sex,Maturation, Sexual
D013076 Sperm Count A count of SPERM in the ejaculum, expressed as number per milliliter. Sperm Number,Count, Sperm,Counts, Sperm,Number, Sperm,Numbers, Sperm,Sperm Counts,Sperm Numbers

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