Citation:

Higuchi, T. T., J. S. Palmer, L E. Gray Jr., AND D. Veeramachaneni. EFFECTS OF DIBUTYL PHTHALATE IN MALE RABBITS FOLLOWING IN UTERO, ADOLESCENT OR POST-PUBERTAL EXPOSURE. TOXICOLOGICAL SCIENCES 72(2):301-313, (2003).

Description:

Effects of dibutyl phthalate in male rabbits following in utero, adolescent, or post-pubertal exposure
Ty T. Higuchi1, Jennifer S. Palmer1, L. Earl Gray Jr2., and D. N. Rao Veeramachaneni1
1Animal Reproduction and Biotechnology Laboratory, Colorado State University, Fort
Collins, CO; and 2National Health and Environmental Effects Research Laboratory,
USEPA, Research Triangle Park, NC.
Abstract
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.

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