Two-generation reproductive toxicity evaluation of dietary 17β-Estradiol (E2; CAS No. 50-28-2) in CD-1 (Swiss) mice

24Citations
Citations of this article
19Readers
Mendeley users who have this article in their library.

Abstract

No information exists on reproductive/developmental effects in mice exposed to dietary 17β-estradiol (E2) over multiple generations. Therefore, under OECD Test Guideline 416 with enhancements, CD-1 mice (F0 generation, 25 mice/sex/group) were exposed to dietary E2 at 0, 0.001, 0.005, 0.05, 0.15, or 0.5 ppm (∼0, 0.2, 1, 10, 30, or 100 μg E2/kg body weight/day) for 8 weeks prebreed, 2 weeks mating, ∼3 weeks gestation, and 3 weeks lactation. At weaning, selected F1 offspring (F1 parents; 25/sex/group) and extra retained F1 males (one per litter) were exposed to the same dietary concentrations and durations as the F0 generation; study termination occurred at F2 weaning; F1/F2 weanlings (up to three per sex per litter) were necropsied with organs weighed. At 0.5 ppm, effects were increased F1/F2 perinatal loss, prolonged F0/F1 gestational length, reduced numbers of F2 (but not F1) litters/group, reduced F1/F2 litter sizes, accelerated vaginal patency (VP) and delayed preputial separation (PPS), increased uterus + cervix + vagina weights (UCVW) in F0/F1 adults and F1/ F2 weanlings, and decreased testes and epididymides weights (TEW) in F1/ F2 weanlings. At 0.15 ppm, effects were increased UCVW in F0/F1 adults and F1/F2 weanlings, accelerated VP, delayed PPS, and reduced TEW in F1/ F2 weanlings. At 0.05 ppm, UCVW were increased in F1/F2 weanlings, and PPS was delayed only in extra retained F1 males. There were no biologically significant or treatment-related effects on F0/F1 parental body weights, feed consumption, or clinical observations, or on F0/F1 estrous cyclicity, F0/F1 andrology, or F1/F2 anogenital distance at any dose. The no observable effect level was 0.005 ppm E2 (∼1 μg/kg/ day). Therefore, the mouse model is sensitive to E2 by oral administration, with effects on reproductive development at doses of 10- 100 μg/kg/day. © The Author 2008. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved.

Cite

CITATION STYLE

APA

Tyl, R. W., Myers, C. B., Marr, M. C., Sloan, C. S., Castillo, N. P., Veselica, M. M., … Hentges, S. G. (2008). Two-generation reproductive toxicity evaluation of dietary 17β-Estradiol (E2; CAS No. 50-28-2) in CD-1 (Swiss) mice. Toxicological Sciences, 102(2), 392–412. https://doi.org/10.1093/toxsci/kfn002

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free