ToxSci Advance Access published online on March 7, 2003
Toxicological Sciences, doi:10.1093/toxsci/kfg036
Toxicological Sciences © Society of Toxicology 2003; all rights reserved
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1 Animal Reproduction and Biotechnology Laboratory, Colorado State University, Fort Collins, CO
* To whom correspondence should be addressed. E-mail: rao{at}colostate.edu.
We evaluated sequelae in male rabbits following exposure to dibutyl phthalate (DBP) at a dose level known to adversely affect testicular function in rodents without causing systemic toxicity. Because rabbits have a relatively long phase of reproductive development simulating that of humans better than rodents and that use of rabbits facilitates multiple evaluations of mating ability and seminal quality we used this animal model. Rabbits were exposed to 0 or 400 mg DBP/kg/day in utero (GD 15-29), and during adolescence (PNW 4-12) and male offspring were examined at 6, 12 and 25 wk of age. Another group was exposed after puberty (for 12 wk) and examined at the conclusion of exposure. The most pronounced reproductive effects were in male rabbits exposed in utero. Male offspring in this group exhibited reduction in number of ejaculated sperm (down 43%; p<0.01), weights of testes (at 12 wk; down 23%; p<0.05) and accessory sex glands (at 12 and 25 wk; down 36%, p<0.01 and 27%, p<0.05), and serum testosterone levels (at 6wk; down 32%, p<0.05); a slight increase in histological alterations of the testis (p<0.05) and a doubling in the percentage (from 16 to 30%, p<0.01) of abnormal sperm; and 1/17 males manifested hypospadias, hypoplastic prostate and cryptorchid testes with carcinoma in situ-like cells. In the DBP group exposed during adolescence, basal serum testosterone levels were reduced at 6 wks (p<0.01) while at 12 wk testosterone production in vivo failed to respond normally to a GnRH challenge (p<0.01). In addition, weight of accessory sex gland was reduced at 12 wk but not at 25 wk after a recovery period; there was a slight increase in the percentage of abnormal sperm in the ejaculate; and 1/11 males was unilaterally cryptorchid. In both of these DBP-treated groups, daily sperm production, epididymal sperm counts, mating ability, and weights of body and non-reproductive organs were unaffected. Thus, DBP induces lesions in the reproductive system of the rabbit with the intrauterine period being the most sensitive stage of life.
© 2003 Society of Toxicology
Reproductive and Developmental Toxicology
Effects of Dibutyl Phthalate in Male Rabbits Following in Utero, Adolescent, or Post-Pubertal Exposure
2 National Health and Environmental Effects Research Laboratory, USEPA, Research Triangle Park, NC
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