Grantee Research Project Results
2005 Progress Report: Impact of Phthalates on the Male: Frog and Rabbit Models
EPA Grant Number: R829429Title: Impact of Phthalates on the Male: Frog and Rabbit Models
Investigators: Veeramachaneni, D. N. Rao
Institution: Colorado State University
EPA Project Officer: Aja, Hayley
Project Period: March 1, 2002 through February 28, 2005 (Extended to February 28, 2007)
Project Period Covered by this Report: March 1, 2005 through February 28, 2006
Project Amount: $852,709
RFA: Children's Vulnerability to Toxic Substances in the Environment (2001) RFA Text | Recipients Lists
Research Category: Children's Health , Human Health , Environmental Justice
Objective:
The objective of this research project is to test the hypothesis that exposure to dibutyl phthalate (DBP) during differentiation of the reproductive system, even at relatively low concentrations, alters reproductive function as adults. This hypothesis is being tested in two animal models, an amphibian, Xenopus laevis, and a non-rodent mammal, the rabbit. The former facilitates transdermal exposure and evaluation of an easy-to-monitor, unique thyroid hormone-dependent event, the metamorphosis, whereas the latter facilitates longitudinal evaluations of hormones, semen parameters, and sexual capacity. Furthermore, rabbits, unlike rodents, have a relatively long infantile period of reproductive development more closely approximating the situation in humans. Dermal route of exposure is particularly pertinent to children’s vulnerability to toxic substances in the environment because children have a greater ratio of surface area to body weight than adults.
Progress Summary:
Frog Model
All phases of experiments using Xenopus laevis were completed and results published or submitted for publication.
Rabbit Model
All animal phases of experimentation were completed. Seminal and endocrine parameters were evaluated and analysed. Sperm morphology and histopathological evaluations of testicular tissue of rabbits are in progress.
The results from studies completed thus far show that: (1) exposure of Xenopus laevis to DBP at concentrations as low as 0.1 ppm, has a pronounced effect on the survival and normal progression of metamorphosis in Xenopus laevis, even when exposed after completion of organogenesis, and impairs spermatogenesis; and (2) developmental exposure of male rabbits to DBP results in germ cell atypia.
Future Activities:
Sperm morphology and histopathological evaluations of all rabbit tissues are being performed during the coming year. No hurdles in the conduct of remaining procedures are anticipated.
Journal Articles on this Report : 3 Displayed | Download in RIS Format
Other project views: | All 16 publications | 4 publications in selected types | All 4 journal articles |
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Higuchi TT, Palmer JS, Gray Jr LE, Veeramachaneni DNR. Effects of dibutyl phthalate in male rabbits following in utero, adolescent, or postpubertal exposure. Toxicological Sciences 2003;72(2):301-313. |
R829429 (2002) R829429 (2005) R829429 (Final) |
Exit Exit |
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Lee SK, Owens GA, Veeramachaneni DNR. Exposure to low concentrations of di-n-butyl phthalate during embryogenesis reduces survivability and impairs development of Xenopus laevis frogs. Journal of Toxicology and Environmental Health, Part A 2005;68(10):763-772. |
R829429 (2004) R829429 (2005) R829429 (Final) |
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Lee SK, Veeramachaneni DNR. Subchronic exposure to low concentrations of di-n-butyl phthalate disrupts spermatogenesis in Xenopus laevis frogs. Toxicological Sciences 2005;84(2):394-407. |
R829429 (2004) R829429 (2005) R829429 (Final) |
Exit Exit |
Supplemental Keywords:
abnormal male sexual differentiation, testicular dysgenesis, human health risk assessment, animal model, animal studies, children, children's environmental health, cryptochidism, dermal contact, dermal exposure, diopathic infertility, exposure, exposure assessment, exposure pathways, fertility, frog deformities, human exposure, human health risk, male reproductive health, phtalates, reproductive development, reproductive effects, reproductive function, reproductive health, risk assessment,, RFA, Health, Scientific Discipline, Toxicology, Health Risk Assessment, Chemistry, Risk Assessments, Disease & Cumulative Effects, Children's Health, Ecological Risk Assessment, Biology, risk assessment, frog deformities, dermal contact, animal model, phtalates, children, fertility, Human Health Risk Assessment, reproductive development, human exposure, children's environmental health, exposure pathways, animal studies, reproductive health, reproductive function, diopathic infertility, exposure assessment, human health riskProgress and Final Reports:
Original AbstractThe perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.