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Assessment of a nonsteroidal aromatase inhibitor, letrozole, in juvenile rats

Beckman, David and Schneider, Marilynn and Decristofaro, Marc and Samadfam, Rana and Smith, Susan and Pouliot, Louise (2013) Assessment of a nonsteroidal aromatase inhibitor, letrozole, in juvenile rats. Birth Defects Research, 98 (5). pp. 374-390. ISSN 1542-9741

Abstract

BACKGROUND: The timing and duration of oral administration of letrozole was designed to encompass the majority of postnatal development in the rat with the intent of evaluating the potential for diverse chronic effects as well as expected effects on skeletal maturation. METHODS: Sprague- Dawley rats were administered letrozole via oral gavage at doses of 0.003, 0.03 and 0.3 mg/kg/day (mkd) on beginning on post partum day (PPD) 7 and up to PPD 91. Clinical signs, body weight, food consumption, developmental, bone, ophthalmology, behavioral, clinical/anatomic pathology, toxicokinetics, and reproductive assessments were conducted. RESULTS: Increases in females and decreases in males were seen for growth (body weight progression and crown-to-rump length) and food consumption. Delays in sexual maturation and adverse effects upon reproductive function were seen in both sexes. Skeletal changes were noted for males and females with recovery for males at 0.003 mkd and females at 0.003 and 0.03 mkd. Pathological changes were limited to adverse effects in the pituitary-adrenal-gonadal axis, correlating with the adverse effects upon reproductive function. CONCLUSIONS: The observed effects in juvenile rats were considered predictable and primarily related to the mechanism of action of letrozole upon estrogen synthesis.

Item Type: Article
Keywords: letrozole; juvenile toxicity; postnatal development; bone effects; rat
Date Deposited: 27 Apr 2016 23:45
Last Modified: 27 Apr 2016 23:45
URI: https://oak.novartis.com/id/eprint/7840

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