Low-dose developmental exposure to bisphenol A alters the femoral bone geometry in wistar rats.
BACKGROUND
Bisphenol A (BPA) is a chemical produced in large volumes for use in manufacturing of consumer products and industrial applications, and an endocrine disruptor known to affect several hormonal systems. Bone produces hormones and is additionally a sensitive hormone target tissue, and is thus potentially sensitive to low doses of endocrine disruptors such as BPA, especially during development.


METHODS
110 pregnant Wistar rats were gavaged with 0; 25 μg; 250 μg; 5000 μg or 50,000 μg BPA/kg bodyweight (bw)/day from gestational day 7 until weaning at postnatal day 22. The three-month-old offspring were sacrificed and right femurs collected for length measurements, geometrical measurements by peripheral quantitative computed tomography (pQCT), as well as for analyses of biomechanical properties using the three-point-bending method.


RESULTS
The femur was elongated in female offspring of dams exposed to 25 or 5000 μg BPA/kg bw/day (1.8% and 2.1%, respectively), and increased cortical thickness (4.7%) was observed in male offspring of dams exposed to 25 μg BPA/kg bw/day, compared to controls (p < 0.005). The biomechanical properties of the bone were not significantly altered.


CONCLUSIONS
In utero and lactational exposure to the lowest BPA dose used in this study altered femoral geometry in both male and female offspring. This was observed at 25 μg BPA/kg bw/day, a dose lower than the Human Equivalent Dose (HED) applied by EFSA to set a temporary TDI (609 μg BPA/kg bw/day), and far lower than the No-Observed-Adverse-Effect-Level (NOAEL) (5000 μg BPA/kg bw/day) on which the US FDA TDI is based.
Department of Medical Sciences, Occupational and Environmental Medicine, Box 256, Uppsala University, SE-751 85 Uppsala, Sweden. Electronic address: margareta.halin@medsci.uu.se.
M H
MH
Lejonklou
Division of Diet, Disease Prevention and Toxicology, Technical University of Denmark, Mørkhøj Bygade 19, DK-2860 Søborg, Denmark.
S
S
Christiansen
Department of Environmental Toxicology, Evolutionary Biology Centre, Box 256, Uppsala University, SE-75105 Uppsala, Sweden.
J
J
Örberg
Department of Medical Sciences, Occupational and Environmental Medicine, Box 256, Uppsala University, SE-751 85 Uppsala, Sweden.
L
L
Shen
Department of Surgical Sciences, Section of Orthopedics, Box 256, Uppsala University, SE-75185 Uppsala, Sweden.
S
S
Larsson
Division of Diet, Disease Prevention and Toxicology, Technical University of Denmark, Mørkhøj Bygade 19, DK-2860 Søborg, Denmark.
J
J
Boberg
Division of Diet, Disease Prevention and Toxicology, Technical University of Denmark, Mørkhøj Bygade 19, DK-2860 Søborg, Denmark.
U
U
Hass
Department of Medical Sciences, Occupational and Environmental Medicine, Box 256, Uppsala University, SE-751 85 Uppsala, Sweden.
P M
PM
Lind
D015502:Absorptiometry, Photon; D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity*; D001696:Biomechanical Phenomena; D015519:Bone Density; D001846:Bone Development / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000633:toxicity*; D005260:Female; D005269:Femur / Q000033:anatomy & histology / Q000187:drug effects* / Q000196:embryology; D006801:Humans; D007774:Lactation; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced*; D051381:Rats; D017208:Rats, Wistar; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds
Bisphenol A (BPA); Bone biomechanics; Bone geometry; Developmental exposure; Endocrine disrupting chemicals (EDCs); Low dose effects