Reproductive Toxicology 29 (2010) 99–105 Contents lists available at ScienceDirect Reproductive Toxicology journal homepage: www.elsevier.com/locate/reprotox Reproductive development and function of female rats exposed to di--butyl-phthalate (DBP) in utero and during lactation Marina T. Guerra a , Wellerson R. Scarano a , Fabíola C. de Toledo b , Janete A.A. Franci c , Wilma De G. Kempinas a,∗ a Department of Morphology, Institute of Biosciences, São Paulo State University, UNESP - Botucatu, São Paulo, Brazil b Graduate Program in Cell and Structural Biology, Institute of Biology, State University of Campinas, UNICAMP - Campinas, São Paulo, Brazil c Department of Morphology, Stomatology and Physiology, School of Dentistry, University of São Paulo, USP - Ribeirão Preto, São Paulo, Brazil article info Article history: Received 7 May 2009 Received in revised form 22 September 2009 Accepted 10 October 2009 Available online 20 October 2009 Keywords: Maternal exposure Di--butyl-phthalate Female offspring Reproduction Uterus Ovary Estrous cycle Sexual behavior abstract Phthalates are environmental contaminants used in the production of plastics, cosmetics and medical devices. Studies on the effects of phthalates on female reproductive health are particularly sparse and mostly restricted to high-dose exposure in rats. In the present study, pregnant rats were treated with 100 mg/kg-d of di--butyl-phthalate (DBP) or only the vehicle (control group), from GD 12 to GD 20 for evaluation of reproductive outcomes and fetal gonads analysis (F0), and from GD 12 to PND 21 to evaluate reproductive development and function on F1 female offspring. Results showed that all parameters were comparable between groups, although there was a significant increase in the fetal weight after DBP exposure. However, the body weight at birth was normal. Based on these data we can conclude that, in these experimental conditions, DBP did not disturb the reproductive development or function of female rats. © 2009 Elsevier Inc. All rights reserved. 1. Introduction Humans are constantly exposed to a wide range of environ- mental contaminants from industrial processes, through air, food, water or contact with a variety of consumer products. In recent years, one class of chemicals used as plasticizers called phthalates have attracted special attention from the scientific community and the general public due to their high production volume, in mil- lions of tons annually, and variety of applications. In addition, they are suspected of acting as endocrine disruptors which signifies that they have the potential to modify normal endocrine func- tion [1–4]. Phthalate esters are liquid plasticizers widely used in flexible polyvinyl chloride (PVC) products, personal care products, cosmetics (perfume, lotions and nail polish), paints, coatings, some pesticide formulations, and pharmaceutical products [5,6] and thus are ubiquitous low-level environmental contaminants [7,8]. ∗ Corresponding author at: Department of Morphology, Bioscience Institute, UNESP, Distrito de Rubião Jr s/n, Botucatu - São Paulo, CEP 18618-000, Brazil. Tel.: +55 014 3811 6264; fax: +55 014 3811 6264. E-mail address: kempinas@ibb.unesp.br (W.D.G. Kempinas). Di--butyl-phthalate (DBP) is a phthalic acid ester used exten- sively as a plasticizer in many products including medical devices [9], flexible plastics (children’s toys, beverage bottles and feed bot- tles) and some cosmetic formulations [10–12]. Human exposure occurs primarily through contaminated food, especially high-fat foods, which may have been in contact with plastic, adhesives, or other packing materials that contain DBP. Herbal preparations and nutritional supplements may also incor- porate phthalates in their formulations. This is especially true for di(2-ethylhexyl) phthalate (DEHP) and DBP. These types of products are typically taken by pregnant women. Pharmaceutical formulations also result in significant human exposure, because various plasticizers are used to coat medicines such as antibiotics, antihistamines and laxatives [13]. Most of the studies related to phthalates are restricted mainly to high-dose exposure [3,14–17], in which the effects are more pronounced. Human and animal exposures to low concentrations of phthalates usually occur after the release of phthalate esters from plastic products and utensils because phthalates are not permanently bound to the polymer matrix [12,18–21]. Phthalate metabolites were detected in the urine of children and adults, in serum, seminal fluid, amniotic fluid, breast milk and saliva [22–27]. Estimates for human exposure to DBP range from 0.84 0890-6238/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.reprotox.2009.10.005