Effects of perinatal loratadine exposure on male rat reproductive organ development
| Autor: | Paul M Vancutsem, Kimberley A. Treinen, Barry S. McIntyre, Richard E. Morrissey |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Male
medicine.medical_specialty Litter Size Endpoint Determination medicine.drug_class Offspring Biology Loratadine Toxicology Antiandrogen Pregnancy Internal medicine Lactation medicine Animals Birth Weight Genitalia Sex Ratio Sexual Maturation Fetal Death Body Weight Anogenital distance Organ Size Androgen Teratology Rats Endocrinology medicine.anatomical_structure Prenatal Exposure Delayed Effects Sucking Behavior Androgens Histamine H1 Antagonists Gestation Female medicine.drug |
| Zdroj: | Reproductive Toxicology. 17:691-697 |
| ISSN: | 0890-6238 |
| Popis: | Normal pre- and postnatal male reproductive development and function is dependent upon testicular androgen production and is sensitive to antiandrogenic perturbations. It was of interest to determine if the H(1) histamine antagonist loratadine had the potential to alter androgen-mediated reproductive development in the rat, a sensitive species for detecting antiandrogenic effects. Loratadine was administered orally by gavage to pregnant Sprague-Dawley rats at doses of 4, 12 or 24 mg/kg from gestation day 7 to postnatal day 4, encompassing the period of androgen-dependent male reproductive development. Vehicle control rats received 0.4% aqueous methylcellulose. Dams were allowed to deliver naturally and rear their offspring until postnatal day 21. On postnatal day 21 male offspring were retained for further evaluation of androgen-dependent endpoints and the female offspring were euthanized and their sex confirmed internally. Males were necropsied from postnatal day 72 to 85. Dams administered 24 mg/kg of loratadine exhibited a transient 45% decrement in maternal body weight gain at the initiation of dosing (gestation days 7-9). Mean pup body weight on postnatal days 1 and 4 were approximately 4% lower than controls. No other effects on offspring growth were observed. Anogenital distance on postnatal day 1 was unaffected by loratadine exposure. Loratadine exposure did not induce the retention of nipples in male rats, affect preputial separation, or induce external malformations, including hypospadias. Seminal vesicle and prostate weights were not decreased by loratadine exposure. These data clearly demonstrate that systemic loratadine exposure, in multiples up to 26 times clinical exposure levels, does not exhibit in vivo antiandrogen activity, as evidenced by the absence of alterations or malformations in androgen-dependent reproductive tissues in male rats exposed to loratadine during the critical period of androgen-dependent development. |
| Databáze: | OpenAIRE |
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